Etofenprox Human Health Risk Assessment DP No. D405380 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: September 12, 2013 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Etofenprox: Section 3 Aggregate Human Health Risk Assessment for a Label 

Amendment to Remove Application Restriction Over Crop, Range, and Pasture 

land. 

PC Code: 128965 

Decision No.: 455901 

Petition No.: 1 E7925 

DP Barcode: D405380 

Registration No.: 2724-807 and 2724-791 

Regulatory Action: Section 3 

Risk Assessment Type: Aggregate 

TXRNo.: NA 

Case No.: NA 

CAS No.: 80844-07-l 

MRIDNo.: NA 40 CFR: § 180.620 

FROM: 

THROUGH: 

TO: 

Kristin Rury, Biologist ¥-~ Meheret Negussie, Chemis;' J ;J<rf-::.FttC 

Barry O'Keefe, Senior Biologist i3~ 0 Jft!l-, 

Myron Ottley, Senior Toxicologist .1fA}v u ....---I' 

Risk Assessment Branch III 

Health Effects Division (7509P) 

Christine C?linger /-); / -...-;f//: . Branch Ch1ef c.t" V!A--<" /?ll..f- ~ 

Risk Assessment Branch III 

v , fr""~-

Health Effects Division (7509P) 

Andrew Ertman, Minor Use Team 

Barbara Madden, Minor Use Team 

Risk Integration, Minor Use, and Emergency Response Branch 

Registration Division (7505P) 

This document provides an assessment of the human health risk resulting from the proposed and 

registered uses of etofenprox. The toxicology reevaluation was performed by Myron Ottley, the 

drinking water assessment was conducted by Charles Peck (EPA Environmental Fate and Effects 

Division (EFED)), the review of the residue chemistry data was conducted by Meheret Negussie, 

the occupational and residential exposure review was conducted by Barry O'Keefe, and the 

dietary and human health risk assessments were conducted by Kristin Rury. 

Page 1 of 46 
Etofenprox Human Health Risk Assessment DP No. D405380 

1.0 Executive Summary ......................................... .... ........ ........................................... ........... 4 

2.0 HED Recommendations ................... ........................................... ... ................................... 6 

2.1 Data De.ficiencies ................ ..................................... ....................................................... 6 

2.2 Tolerance Considerations ............................... ............................................................... 6 

2.2.1 Enforcement Analytical Method ............................................................................... 6 

2.2.2 Recommended Tolerances .. ........................................... ............... ............................. 7 

2.2.3 Revisions to Petitioned-For Tolerances .... .... ....... .... ................................................. 8 

2.2.4 International Harmonization ............ ............................................... .......................... 8 

3.1 Chemical Identity .................................. ................ .............................. ..... .... .... ........ .... .. 9 

3.2 Physical/Chemical Characteristics ................................................... .......................... 10 

3.3 Pesticide Use Pattern ............................... ............ ................................................ ........ . I 0 

3.4 Anticipated Exposure Pathways ................................... ........ .... .................................. 11 

3.5 Consideration of Environmental Justice .. .... ....... ............................................ .... ....... 11 

4.0 Hazard Characterization and Dose-Response Assessment.. ..... .... .... ........................... 12 

4.1 Summary of Toxicological Effects ............... .... ....... ................................................ .... 12 

4.2 Safety Factor for Infants and Children (FQPA Safety Factor) ....... ........ .... ........ .... 14 

4.2.1 Completeness of the Toxicology Database .............................................................. 14 

4.2.2 Evidence of Neurotoxicity ............................ ............................................................ 14 

4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ........ 15 

4.2.4 Residual Uncertainty in the Exposure Database ......... .... ................ .... .................. 15 

4.3 Toxicity Endpoint and Point of Departure Selections .............................................. 16 

4.4 Recommendation for Combining Routes of Exposure for Risk Assessment.. .......... . 17 

5.0 Dietary Exposure and Risk Assessment.. ......... ................................ .............................. 18 

5.1 Residues of Concern Summary and Rationale ................................... ....................... 18 

5.2 Food Residue Profile ............................. ........ .... .... .... ........ ........................................ ... 18 

5.3 Water Residue Profile ................... ....................................................................... ........ 19 

5.4 Dietary Risk Assessment ...................................... ........... ........ .... ................................. 20 

5.4.1 Description of Residue Data Used in Dietary Assessment .................................... 20 

5.4.2 Percent Crop Treated Used in Dietary Assessment ............................ .................. 20 

5.4.3 Acute Dietary Risk Assessment.. ............ ........ ... .... ................ .... .... .......................... 21 

5.4.4 Chronic Dietary Risk Assessment .. ......................................................................... 21 

5.4.5 Cancer Dietary Risk Assessment.. ........................................................................... 22 

5.4.6 Summary Table .................................................................. .... ......... ....... .... .... ........... 22 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 22 

6.1 Residential Handler Exposure ..................................... .... .... ........... .. .. .... ........ .... ........ 23 

6.2 Post-Application Exposure ........... .... ........................................................................... 24 

6.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios) ................... 25 

6.4 Residential Risk Estimates for Use in Aggregate Assessment.. ................................ 26 

6.5 Residential Bystander Post-application Inhalation Exposure ................................. 27 

6.6 Spray Drift .............................................................................. .... ... ................. .... .... .... .. 27 

7.0 Aggregate Exposure/Risk Characterization .... .... ....................... ................ ................... 28 

7.1 Acute Aggregate Risk ..................................... ............................................... .... .... ....... 28 

7.2 Short- and Intermediate-Term Aggregate Risk ................................ ........................ 28 

7.3 Chronic Aggregate Risk .............................................................................................. 29 

8.0 Cumulative Exposure/Risk Characterization ............................................................... 30 

9.0 Occupational Exposure/Risk Characterization ............................................................ 31 

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Etofenprox Human Health Risk Assessment DP No. D405380

Page 3 of 46

9.1 Short-/Intermediate-Term Handler Risk................................................................... 31

9.2 Short-/Intermediate-Term Post-Application Risk .................................................... 32

9.2.2 Inhalation Post-Application Risk............................................................................ 32

10.0 References......................................................................................................................... 32

Appendix A. Toxicology Profile and Executive Summaries .................................................. 34

A.1 Toxicology Data Requirements................................................................................... 34

A.2 Toxicity Profiles............................................................................................................ 35

Appendix B. Physical/Chemical Properties and Etofenprox Metabolites............................ 41

Appendix C. Review of Human Research................................................................................ 43

Appendix D. Residential Exposure/Risk Summary Tables.................................................... 44
Etofenprox Human Health Risk Assessment DP No. D405380

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1.0 Executive Summary

Introduction

Etofenprox [2-(4-ethoxyphenyl)-2-methylpropyl 3-phenoxybenzyl ether], is a synthetic 

pyrethroid ether insecticide (Group 3). Etofenprox differs in structure from other synthetic 

pyrethroids in that it contains an ether moiety rather than an ester moiety. The mode of action 

against insects is very similar to that of other pyrethroids. The main action site is the neuronal 

axon. Etofenprox is currently registered for one food use on rice and the following nonfood 

uses: as an ultra low volume (ULV) spray to control adult mosquitos except in areas with 

growing crops; as a spot treatment for cats and dogs; as indoor and outdoor residential uses; and 

for use in non-food handling areas of commercial food-handling establishments. Registered 

products include emulsifiable concentrates (ECs), soluble concentrates (SCs), granulars, 

pressurized liquid (PrL), and ready-to-use (RTU) formulations applied as sprays, and foggers. 

Use profile

The Interregional Research Project No. 4 (IR-4) submitted a petition (1E7925) to remove the 

cropland and pastureland application restrictions from the Zenivex mosquito adulticide labels 

(EPA Reg. Nos. 2724-791 and 2724-807). These products are labeled for use only by federal, 

state, tribal, or local government officials; by persons certified in the appropriate category or 

otherwise authorized by the state or tribal lead pesticide regulatory agency to perform adult 

mosquito control applications; or by persons under direct supervision of those authorized by the 

state, tribal, or local pesticide regulatory agencies. The proposed/amended labels allow for ULV 

applications by aerial and ground equipment at a maximum application rate of 0.007 lb ai per 

acre over crop, pasture, and range land. Up to 25 applications may be made per year, with only 

two applications allowed per week, and only four applications per month. A maximum of 0.18 

lb ai/A of etofenprox may be applied per site per year. There is no required personal protective 

equipment (PPE) listed on the label, nor a proposed restricted entry interval (REI). 

Hazard Assessment

The major target organs of etofenprox are the liver, thyroid, kidney, and hematopoietic system. 

Etofenprox has low acute toxicity via the oral, dermal, and inhalation routes. It is not an acute 

eye or skin irritant and is not a dermal sensitizer; however, etofenprox does cause skin irritation 

after repeated exposure. Evidence of quantitative and qualitative susceptibility of offspring was 

not observed, and therefore, the Food Quality Protection Act (FQPA) 10X safety factor was 

reduced to 1X. Etofenprox was classified as “not likely to be carcinogenic to humans at doses 

that do not alter rat thyroid hormone homeostasis” and, therefore, a quantitative cancer risk 

assessment is not required. The level of concern (LOC) for all exposure scenarios is a margin of 

exposure (MOE) <100.

Residential Exposure 

From the proposed/amended mosquito adulticide use there are potential short-term postapplication exposures to adults and children. Additionally, all of the existing residential uses 

have been reassessed to reflect updates to the HED 2012 Residential SOPs1. Neither the 

proposed/amended mosquito adulticide use nor any of the currently registered uses result in any 

residential handler or post-application risk estimates of concern. 

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
Etofenprox Human Health Risk Assessment DP No. D405380

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Dietary Exposure 

An acute dietary endpoint was not identified in the etofenprox toxicity database. Therefore, an 

acute dietary exposure assessment was not conducted. The chronic dietary (food and drinking 

water) exposure assessment for etofenprox assumed modeled residue estimates for all food 

commodities and recommended tolerance-level residues for livestock commodities. The 

assessment also incorporated estimated percent crop treated (%CT) values, and used default 

processing factors. Estimated drinking water concentrations (EDWCs) from EFED (1.2 μg/L) 

were also included. The results of the chronic analysis indicate that the chronic dietary (food and 

drinking water) exposure and risk does not exceed HED’s LOC [i.e., <100% of the chronic 

population adjusted dose (cPAD)] for the U.S. population and all population subgroups. The 

resulting chronic dietary (food and drinking water) risk estimates were 8.6% for the U.S. 

population, and 32% for children 1 to <2 years old, the highest exposed population subgroup. 

Etofenprox is classified as “Not Likely to be Carcinogenic to Humans”; therefore, a cancer 

dietary risk assessment is not required.

Aggregate Exposure

There is potential short-term and chronic exposure to etofenprox via dietary (which is considered 

background exposure) and residential (which is considered primary) exposure pathways. 

Because of the registered indoor uses of etofenprox, intermediate-term post application 

exposures are possible. However, since the short- and intermediate-term endpoints and PODs 

for inhalation and oral routes are the same, the short-term exposure and risk estimates are 

considered to be protective of potential intermediate-term exposure and risk. The short- and 

intermediate-term adult aggregate MOE is 1,700 and is not of concern to HED. The short- and 

intermediate-term term children 1 to <2 years old aggregate MOE, including incidental oral and 

post-application inhalation exposures from using etofenprox in residential settings, is 420 and is 

not of concern to HED. There is potential chronic/long-term exposure to etofenprox via dietary 

and residential exposure pathways for children 1 to <2 years old. The chronic aggregate MOE 

for children 1 to <2 years old, including incidental oral exposures from using etofenprox to treat 

companion animals, is 180 and is not of concern to HED. For future uses of etofenprox, further 

refinement using etofenprox-specific field trial data to estimate potential residues resulting from 

mosquito adulticide use near growing food commodities would further refine the dietary and 

aggregate exposure assessment. 

Occupational Exposure 

There is potential for short- and intermediate-term occupational exposure to etofenprox during 

handling activities (e.g. mixing, loading, application). Dermal toxicity was not identified, so a 

dermal exposure assessment was not conducted. At baseline (no respirator), short-term 

inhalation MOEs range from 8,600 to 240,000, and are not of concern to HED. For the proposed 

mosquito adulticide use, workers are not expected to reenter treated areas following application, 

and therefore, an assessment for post-application exposure is not required. 

Review of Human Research
Etofenprox Human Health Risk Assessment DP No. D405380

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

intentionally exposed to a pesticide or other chemical. For citations of these data, see Appendix 

C. 

Environmental Justice Considerations

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. 

2.0 HED Recommendations

HED can recommend for a registration and tolerances for the use of etofenprox as a mosquito 

adulticide near and over crop, pasture, and range land. In conjunction with establishment of the 

recommended tolerance on food commodities, the existing tolerance on rice grain should be 

removed from 40 CFR 180.620. Additional data are needed as outlined in Section 2.1 below, 

and the specific tolerance recommendations are discussed in Section 2.2. 

2.1 Data Deficiencies

860.1550 Proposed Tolerances

The proposed tolerance for etofenprox in/on all food and feed commodities at 0.5 ppm is 

not appropriate. A revised Section F needs to be submitted to propose tolerances as 

listed in Table 2.2.2.

The petitioner needs to submit a revised Section F to propose tolerances for livestock 

commodities. 

The following deficiencies would refine the recommended tolerances on all food and feed 

items, and refine the dietary exposure assessment in the future:

860.1500 Crop Field Trials

The field trial data submitted with the current petition was inadequate. However, HED 

has conservatively estimated tolerances following mosquito adulticide ULV applications 

near growing food and feed crops. Additional field trials reflecting multiple applications 

with both ground and aerial equipment would refine the recommended tolerances and the 

dietary exposure assessment. The Registrant should submit a protocol for the 

recommended field trials to the Agency prior to conducting the studies. 

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method
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Crop commodities: An LC/MS/MS method, entitled “Analytical Method Validation for 

Determination of Etofenprox and α-CO in Rice and Rice Straw” which was based on Wildlife 

International, Ltd. 236C-136 method, with minor modifications is available for the enforcement 

of tolerances for residues of etofenprox on rice. The data collection methods which are 

sufficiently similar to the enforcement method do not require separate independent laboratory 

verification and can be used to enforce tolerances. 

The LC/MS/MS has undergone a successful petition method validation (PMV) review without a 

laboratory trial by the Analytical Chemistry Branch/Biological and Economic Analysis Division 

(ACB/BEAD) (memo from C. Stafford dated 06/25/08). ACB/BEAD has determined that the 

LC/MS/MS appears to meet the requirements for an acceptable tolerance enforcement method 

with two ion transitions for etofenprox: m/z 359→183 and 177→107.

The multiresidue methods may be suitable for determining residues of etofenprox for dietary 

exposure assessment and tolerance enforcement on rice.

Livestock Commodities: The proposed GC/MS enforcement method (RCC Study NO. 791245) in 

combination with the GC/MS confirmatory method (using a different column), meets the OPPTS 

Residue Chemistry Test Guidelines for acceptable tolerance enforcement methods (SOP Number 

ACB-019). The method may be forwarded to FDA for inclusion in the Pesticide Analytical 

Manual PAM, Vol. II.

2.2.2 Recommended Tolerances

In connection with this petition, IR-4 requested the establishment of permanent tolerances of 

etofenprox of 0.5 ppm for all food and feed commodities. Because of the reasons listed in 

Section 2.2.3, HED recommends that tolerances on all food and feed commodities be established 

at 5.0 ppm. Upon establishment of food commodities tolerances, the current tolerance on rice 

grain (0.01 ppm) should be removed. HED also recommends that permanent tolerances be 

established for livestock commodities at the following levels: 

Table 2.2.2. Tolerance Summary for Etofenprox

Commodity Proposed/Established

Tolerance (ppm)

Recommended 

Tolerance 

(ppm)

Comments; Correct Commodity 

Definition

Food commodities 0.5 5.0

Feed commodities 0.5 5.0

Rice, grain 0.01 - Remove individual tolerance – covered by 

all-crop tolerance

Additional Livestock Commodity Tolerances That Need to be Proposed/Established

Eggs None 0.40 Eggs

Hog, fat 4.0 Hog, fat

Hog, meat 0.20 Hog, meat

Hog, meat byproducts 4.0 Hog, meat byproducts
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Table 2.2.2. Tolerance Summary for Etofenprox

Commodity Proposed/Established

Tolerance (ppm)

Recommended 

Tolerance 

(ppm)

Comments; Correct Commodity 

Definition

Fat of (cattle, goat, 

horse, and sheep)

10.0 Cattle, fat; Goat, fat; Horse, fat; Sheep, 

fat

Meat of (cattle, goat, 

horse, and sheep)

0.40 Cattle, meat; Goat, meat; Horse, meat; 

Sheep, meat

Meat byproducts of 

(cattle, goat, horse, and 

sheep)

10.0 Cattle, meat byproducts; Goat, meat 

byproducts; Horse, meat byproducts;

Sheep, meat byproducts

Milk 0.60 Milk

Poultry, fat/skin 1.0 Poultry, fat

Poultry, meat 0.01 Poultry, meat

Poultry, meat 

byproducts 1.0 Poultry, meat byproducts

2.2.3 Revisions to Petitioned-For Tolerances

To allow application over pasture, range, and crop land, limited field trials were conducted on 

alfalfa, pasture grass, leaf lettuce, and snap beans. However, the submitted trials did not reflect 

the proposed use pattern; there was only one aerial application of etofenprox per site (0.007 lb 

ai/A). The proposed tolerance at 0.5 ppm was estimated using these field trial data. The proposed 

etofenprox labels permit multiple ground and aerial applications (up to 25 applications) over 

agricultural areas per year. 

Subsequently, IR-4 submitted modeling results using the Terrestrial Residue Exposure Model 

(TREX) which estimated residues following repeated ULV applications and concluded residues 

were likely to peak at 1.5 ppm following repeated aerial applications to agricultural crops. Based 

on EFED’s evaluation, HED estimated an upper-bound crop residue estimate of 5.0 ppm 

following repeated ULV aerial and ground applications (C. Peck, D407817, 03/28/2013). 

The tolerance recommendations, revised to 5.0 ppm from the proposed 0.5 ppm based on residue 

estimates generated by IR-4 and EFED, are outlined in Table 2.2.2. 

2.2.4 International Harmonization

There are no Canadian Maximum Residue Limits (MRLs) established for residues of etofenprox. 

Codex has established etofenprox MRLs on several crop and livestock commodities at levels that 

range from 0.01-8.0 ppm. 

Codex MRLs are based on field trial data from foliar applications of etofenprox (EC and SC 

formulations) and granular broadcast applications (paddy rice). These trials were conducted 

mainly in Europe, Brazil, USA (rice), and Japan (rice). The Organization for Economic 

Cooperation and Developmental (OECD) MRL calculator was used to estimate the MRLs.

Codex and U.S. MRLs/tolerances could not be harmonized due to differences in the use pattern 
Etofenprox Human Health Risk Assessment DP No. D405380

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used to derive the tolerances. Codex MRLs were based on field trial data whereas the US 

tolerances were based on application over crops using modeling estimates. 

3.0 Introduction

Etofenprox [2-(4-ethoxyphenyl)-2-methylpropyl 3-phenoxybenzyl ether] is a synthetic 

pyrethroid ether insecticide. Etofenprox differs in structure from other synthetic pyrethroids in 

that it contains an ether moiety rather than an ester moiety. The mode of action against insects is 

very similar to that of other pyrethroids. The main action site is the neuronal axon. Etofenprox 

is currently registered for one food use on rice and the following nonfood uses: spot treatment 

for cats and dogs; indoor and outdoor residential use; and use in non-food handling areas of 

commercial food-handling establishments. Registered products include ECs, SCs, granulars, 

pressurized liquid (PrL), and ready-to-use (RTU) formulations applied as sprays, and foggers. 

Two products containing etofenprox are currently registered for mosquito control, a 4% 

emulsion formulation: Zenivex E4RTU, 4% EPA Reg. No. 2724-807; and a 20% emulsion

formulation: Zenivex E20, 20% EW formulation; EPA Reg. No. 2724-791. The current use does 

not allow treatments in or over agricultural areas. IR-4, on behalf of the Agricultural Experiment 

Station of California, requested a label amendment so that applications are permitted to 

agricultural crops, pasture and rangeland. In connection with this request, the petitioner requests

the establishment of permanent tolerances for residues of the insecticide etofenprox 2-(4-

ethyoxyphenyl)-2-methylpropyl 3-phenoxybenzyl ether in/on all food commodities at 0.5 ppm. 

Exposure to etofenprox has been evaluated by HED using the available field trial data, modeling, 

and current exposure inputs. HED has also reevaluated exposure to etofenprox for the existing 

residential uses using the revised Residential SOPs2. 

3.1 Chemical Identity

Table 3.1. Test Compound Nomenclature.

Compound

Common name Etofenprox

Company experimental name MTI-500

IUPAC name 2-(4-Ethoxyphenyl)-2-methylpropyl 3-phenoxybenzyl ether

CAS name 1-[[2-(4-Ethoxyphenyl)-2-methylpropoxy]methyl]-3-phenoxybenzene

CAS registry number 80844-07-1

End-use products (EP) Zenivex E20, 20% EW formulation (EPA Reg. No. 2724-791); Zenivex E4RTU, 

4% (EPA Reg. No. 2724-807)

 

2 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html

CH2

CH3

CH3

O CH2

O

C2H5O
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Table 3.1. Test Compound Nomenclature.

Chemical structure of α-CO 

metabolite

IUPAC name 2-(4-Ethoxyphenyl)-2-methylpropyl-3-phenoxybenzoate

3.2 Physical/Chemical Characteristics

Etofenprox has a log octanol/water partition coefficient (log Kow) of 6.9 and is considered 

relatively insoluble in water. Additionally, etofenprox has a molecular weight of 376.49 g/mol; 

therefore, the potential to cross biological barriers is somewhat limited. The vapor pressure of 

etofenprox is considered low (2.5×10-8 mm Hg at 25 oC), limiting the potential for volatilization. 

The physiochemical properties of etofenprox are summarized in Appendix B. 

3.3 Pesticide Use Pattern

IR-4 has submitted two draft amended labels removing the restriction from use over crop, range, 

and pasture land. The two end-use products are a 4% emulsion formulation (RF2146 RTU, EPA 

Reg. No. 2724-807) and a 20% emulsion (RF2056 OL, EPA Reg. No. 2724-791). These 

products are labeled for use only by federal, state, tribal, or local government officials; by 

persons certified in the appropriate category or otherwise authorized by the state or tribal lead 

pesticide regulatory agency to perform adult mosquito control applications; or by persons under 

direct supervision of those authorized by the state, tribal, or local pesticide regulatory agencies. 

Etofenprox is currently registered for ULV applications by aerial and ground equipment at a 

maximum application rate of 0.007 lb ai per acre to control adult mosquitoes, midges and black 

flies. The proposed labels allow for multiple applications over crop, pasture, and range land up 

to 25 times per year, with only two applications in any given week, and only four applications 

per month. The maximum amount allowed per site per year is 0.18 lb ai/A. The proposed use 

directions are summarized in Table 3.3. 

CH2

CH3

CH3

O C

O

C2H5O

O
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Table 3.3. Summary of Directions for Use of Etofenprox for Mosquito Control.

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

Mosquito Adulticide

Broadcast

Ground, 

Aerial

4% E

[2724-807]

20% E

[2724-791]

0.00175-

0.007 25 0.18 0

Undiluted only [2724-807];

diluted with oil only [2724-

791].

Applications are limited to 4 

applications/month and 2 

applications within a 7-day 

interval.

3.4 Anticipated Exposure Pathways

Humans may be exposed to etofenprox in food and drinking water, since etofenprox may be 

applied as a spray over growing crops and these applications may result in etofenprox reaching 

surface and ground water. There are registered residential uses of etofenprox so there is 

exposure to residential handlers and those entering treated areas following application. In 

occupational settings, applicators may be exposed while handling etofenprox. There is also 

potential for post-application exposure for workers re-entering treated fields. 

Risk assessments have been completed for existing uses of etofenprox. This risk assessment 

considers all of the aforementioned exposure pathways based on the proposed new uses of 

etofenprox, but also considers existing uses of etofenprox, particularly in the dietary and 

residential exposure assessments. 

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 United States Department of 

Agriculture’s (USDA’s) National Health and Nutrition Examination Survey (NHANES), 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 and ethnic group. 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 following application are evaluated. Further considerations 
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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 patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Since the last risk assessment, (J. Arthur, D343064, 08/13/2008), immunotoxicity studies with 

rats and mice have been submitted (V. Chen, D385299, 03/23/2011). The new immunotoxicity 

data did not alter the endpoints or points of departure listed in the last risk assessment. 

Etofenprox (2-(4-ethoxyphenyl)-2-methylpropyl-3-phenoxybenzylether) is classified as a 

pyrethroid ether insecticide. Naturally occurring pyrethrins and the synthetic pyrethroids 

(collectively called ‘pyrethroids’) are grouped for purposes of cumulative risk assessed based on 

the following shared characteristics: 1) Common structure - Pyrethrins and pyrethroids share a 

common structure; acid and alcohol moieties joined through an ether linkage; 2) Sodium channel 

disruption - In vitro studies demonstrate the ability of pyrethroids to modify mammalian sodium 

channel kinetics, leading to alterations in membrane excitability and firing potentials; 3) 

Neurotoxic Effects - Pyrethroid toxicity is manifested through neurological syndromes described 

as either T (fine tremors), CS (choreoathetosis and salivation), or some combination thereof, 

depending on the structure. Open literature supports a correlation between the modification in 

sodium channel kinetics and the resulting syndrome.

Etofenprox is not included in the pyrethroid common mechanism grouping or included in the 

cumulative risk assessment because etofenprox does exhibit these key characteristics. 

Etofenprox is an ether compound; pyrethroids are esters. Etofenprox exposure does not result in 

the neurotoxic syndromes typical of pyrethroids and no available data suggest the molecular 

target for etofenprox is the sodium channel. 

4.1 Summary of Toxicological Effects

In the mammalian toxicology database, the major targets of etofenprox are the liver, thyroid, 

kidney, and hematopoietic system. Results from subchronic and chronic feeding studies in rats 

indicate that males may be more sensitive to treatment-related effects of etofenprox than females. 

All subchronic and chronic toxicity including carcinogenicity studies showed adverse effects 

(organ weights, histopathology, biochemistry, hematology, and clinical chemistry) in two or 

more of the target organs/systems. Additionally, decreases in body weights and food 

consumption were observed in most of the studies. 

In a mouse carcinogenicity study, the kidney was the most sensitive target organ, especially in 

males, and many deaths were attributed to renal lesions. Males showed a positive trend in renal 

cortical adenomas alone and in combined carcinomas and adenomas; however, tumor incidence 

was within the historical control range. Other effects included decreased body and thymus gland 

weights, and increased liver, spleen, and pituitary gland weights. Microscopic changes included 

centrilobular hepatocyte enlargement. 
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A prenatal developmental toxicity study in rabbits showed no quantitative/qualitative evidence of 

increased susceptibility in offspring, in that the developmental effects were seen at doses that 

resulted in maternal toxicity, including death. There was no indication of increased 

susceptibility of offspring in the one-generation/developmental study in rats. In the 

developmental portion of the study, effects were seen in maternal animals, while no effects were 

observed in the offspring. In the two-generation reproductive toxicity study in rats, there was 

also no evidence of increased susceptibility of offspring.

An acute neurotoxicity study in the adult rat revealed no treatment-related effects. The 

subchronic neurotoxicity study in the rat showed decreased body weight gains, increased liver 

weights in all dose groups, and increased incidence of rearing behavior in males and abnormal 

gait in females. The developmental neurotoxicity study in rats showed increased rearing 

behavior in mothers at the highest dose tested. In offspring, eye abnormalities were observed at 

the high-dose level and effects on motor/locomotor activity and auditory startle response 

observed at the high-dose level. 

The immunotoxicity studies in the rat and mouse were both negative for immunotoxicity. 

The cancer classification for etofenprox is “Not likely to be carcinogenic to humans at doses 

that do not alter rat thyroid hormone homeostasis.” This decision was based on the 

following considerations: (i) Treatment-related thyroid follicular cell tumors were seen in both 

male and female rats at a dose level considered to be adequate, and not excessive, to assess 

carcinogenicity; (ii) No treatment-related tumors were seen in male or female mice when tested 

at a dose that was considered adequate to assess carcinogenicity; (iii) there is no mutagenicity 

concern for etofenprox based in vivo or in vitro assays; (iv) the non-neoplastic toxicological 

evidence (i.e., thyroid growth and thyroid hormonal changes) indicates that etofenprox disrupts 

the thyroid-pituitary hormonal status, and (v) rats are substantially more sensitive than humans to 

the development of thyroid follicular cell tumors in response to thyroid hormone imbalance. The 

overall weight-of-the-evidence was considered sufficient to indicate that etofenprox induced 

thyroid follicular tumors through an antithyroid mode of action. The quantification of 

carcinogenic potential is not applicable.

Etofenprox has low acute oral (Toxicity Category IV), dermal (Toxicity Category III) and 

inhalation (Toxicity Category IV) toxicity in dogs, rabbits and rats, respectively. Etofenprox is 

neither an acute eye nor dermal irritant (Toxicity Categories IV), or an acute dermal sensitizer. 

However, skin irritation was observed after repeated exposure to etofenprox in rabbits. The 

acute toxicity of etofenprox technical (TGAI), as well as the overall acute and chronic toxicity 

profile for etofenprox, are summarized in Appendix A.2 of this document. 

As a class, pyrethroids are metabolized rapidly in mammals and no cumulative effects are 

observed in rats following daily dosing at moderately effective concentrations for 30 days 

(Crofton and Reiter, 1984). Etofenprox is metabolized via oxidative pathways and conjugation 

(glucuronidation and sulfation). The majority of absorbed etofenprox is excreted via the bile. A 

dermal absorption factor (DAF) was determined to be 7.0%.
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4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

Based on the hazard and exposure data, the etofenprox risk assessment team has recommended 

that the FQPA safety factor be reduced to 1X because there is a complete toxicity database for 

etofenprox and exposure data are complete or are estimated based on data that reasonably 

account for potential exposure. There is no evidence of susceptibility following in utero and/or 

postnatal exposure in the developmental toxicity studies in rats or rabbits, nor in the 2-generation 

rat reproduction study. Although infants and children are generally more susceptible to thyroid 

hormone perturbations (thyroid toxicity) by virtue of their developmental stage, the selected 

regulatory PODs are protective of these effects (Section 4.3). Therefore, the human health risk 

assessment is protective of thyroid toxicity and neurotoxicity. 

4.2.1 Completeness of the Toxicology Database

The toxicology database used to assess pre- and postnatal exposure to etofenprox is considered 

adequate. The following acceptable studies are available to support this determination: a 

developmental toxicity study in rabbits, a developmental toxicity/one-generation reproduction 

study in rats, a two-generation reproduction study in rats, and a developmental neurotoxicity 

study in rats. In addition, the database includes acute and subchronic neurotoxicity studies and 

an immunotoxicity study.

4.2.2 Evidence of Neurotoxicity

An acute neurotoxicity study in the adult rat revealed no treatment-related effects. The 

subchronic neurotoxicity study in the rat showed decreased body weight gains, increased liver 

weights in all dose groups, and increased incidence of rearing behavior and abnormal gait, all in 

the absence of histopathological changes. The developmental neurotoxicity study in rats showed 

increased rearing behavior in mothers. In offspring, eye lesions (including sclera and lens 

hemorrhage), which are sometimes associated with aggressive maternal behavior, were observed 

prior to weaning at the highest dose tested. Effects on motor/locomotor activity and auditory 

startle response were also observed in the high-dose treatment groups on PND 58. These latter 

isolated, post-ontogenic effects of treatment are not presumed to occur following a single dose. 

Evidence of neurotoxicity was also observed in other studies. In a subchronic mouse study 

piloerection, hunched posture, lethargy, body tremors, and an unsteady gait were noted in both 

sexes above the limit dose. The rat developmental study showed increased salivation in all 

treatment groups of the F0 generation and decreased (non-statistically significant) mobility (both 

sexes) and rearing behavior (males) in the F1 generation. In the 2-generation reproduction study 

F1 pups exhibited clinical signs of body tremors, lethargy, unsteady gait, and abnormal 

movements during most of the lactation period at the high dose.

However, residual concern for neurotoxicity is low based on the following: (1) signs of

neurotoxicity in the database occur only at the high dose level in each study; (2) the studies show 

clear and well-defined NOAELs; (3) the signs of neurotoxicity are well-characterized in terms of 
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their effects in offspring; and (4) the PODs used for risk assessment are protective of 

neurotoxicity seen in the database. 

No systemic toxicity was observed in the 28-day dermal study in rabbits up to 1000 mg/kg/day. 

In this study, clinical signs were evaluated and signs such as piloerection, hunched posture, 

lethargy, body tremors, an unsteady gait and salivation, seen in the oral repeated dose studies 

discussed above, were not observed. With neurotoxic signs occurring only at high doses in the 

oral studies and a DAF of 7% for etofenprox, neurotoxic manifestations via the dermal route are 

not expected below the limit dose. Therefore, concern for neurotoxicity following dermal 

exposure is low.

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

There is no indication of increased quantitative or qualitative susceptibility of the developing 

offspring in toxicology database for etofenprox. Developmental effects were seen at doses that 

caused maternal toxicity. No developmental effects were seen in the rat onegeneration/developmental study. In the two-generation reproduction toxicity study, toxicity in 

the offspring occurred at the level of parental toxicity (increased organs weights and associated 

pathological changes occurred in both the pups and parents). In the developmental neurotoxicity 

study in rats, the observed eye abnormalities associated with body injuries could not be 

disassociated from possible altered, treatment-related maternal behavior.

4.2.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties with respect to the exposure database for the following 

reasons:

The chronic dietary exposure assessment utilizes modeled and tolerance-level residues that 

assume the conservative deposition onto surrounding crops following a ULV mosquito 

adulticide application. The dietary assessment also assumes conservative, upper-bound %CT 

estimates for the proposed uses. By using these screening level assessments, actual 

exposures/risk are not expected to be underestimated;

The drinking water assessment utilizes water concentration values generated by models and 

associated modeling parameters, which are designed to provide conservative, health 

protective, high-end estimates of water concentrations, which are not likely to be exceeded; 

and 

The residential post-application assessment is based upon the Residential SOPs, including 

surrogate study data. These data are reliable and are not expected to underestimate risk to 

adults or children. The Residential SOPs are based upon reasonable “worst-case” 

assumptions and are not expected to underestimate risk.

While the residue field trials do not reflect the proposed use pattern, the Agency is confident 

that the modeled residues and subsequent tolerances are conservative and protective of any 

residues resulting from repeated mosquito adulticide applications near growing food and feed 

crops. 
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4.3 Toxicity Endpoint and Point of Departure Selections

There have been no changes to the prior dose-response assessment. 

In this risk assessment, long-term residential dermal exposure was examined as a consequence of 

spot-on treatment to pets in geographical regions where the climate is warm year-round. A 

dermal endpoint was not identified for short- intermediate- and long-term exposures, because 1) 

dermal penetration has been shown to be low (7%, corroborated by the low water solubility of 

22.5 μg/L) and is not expected to increase with time, and 2) the absence of systemic effects in 

the 28-day dermal study in rabbits at dose levels up to the limit dose (1000 mg/kg/day). 

Therefore, a revision of long-term dermal risk assessment is not necessary.

Also in this risk assessment, long-term incidental oral exposure was examined as a consequence 

of children being exposed to pets that are treated for fleas all year. The POD selected for longterm incidental oral exposures to children from treated pets was a NOAEL of 3.7 mg/kg/day 

from the combined chronic toxicity and carcinogenicity study in rats based on increased thyroid 

weights.

Table 4.3.1. Summary of Toxicological Doses and Endpoints for Etofenprox for Use in Dietary and NonOccupational Human Health Risk Assessments.

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/F

QPA Safety 

Factors

RfD, PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological Effects

Acute Dietary 

(General 

Population, 

including 

Infants and 

Children)

N/A No acute dietary endpoint was identified

Chronic 

Dietary (All 

Populations)

NOAEL = 

3.7 mg/kg/day

FQPA = 1x

UFA = 10x

UFH = 10x

cRfD = 

0.037 mg/kg/day

cPAD = 

0.037 mg/kg/day

Combined Chronic Toxicity /Carcinogenicity 

Study in Rat (MRID No. 40449707)

LOAEL = 25.5 mg/kg/day based on increased 

thyroid weights. Related to increased liver 

weights and histopathology changes in liver 

and thyroid that occurred at the higher dose.

Incidental Oral 

Short- and 

IntermediateTerm (1-30 

days and 1-6 

months)

NOAEL =

20 mg/kg/day

FQPA = 1x

UFA = 10x

UFH = 10x

LOC for MOE 

≤ 100

Subchronic Oral Toxicity in Rat 

(MRID No. 40449703)

LOAEL = 120 mg/kg/day based on decreased 

body weight gain, increased liver and thyroid 

weights with corresponding histopathology, 

changes in hematology and clinical chemistry.

Incidental Oral 

Long-Term 

(>6 months)

NOAEL = 

3.7 mg/kg/day

FQPA = 1x

UFA = 10x

UFH = 10x

cRfD = 

0.037 mg/kg/day

cPAD = 

0.037 mg/kg/day

Combined Chronic Toxicity /Carcinogenicity 

Study in Rat (MRID No. 40449707)

LOAEL = 25.5 mg/kg/day based on increased 

thyroid weights. Related to increased liver 

weights and histopathology changes in liver 

and thyroid that occurred at the higher dose.

Dermal (All 

durations) N/A

No systemic toxicity was identified in the 

dermal 28-day study; Highest Dose Tested was 

1000 mg/kg/day.
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Table 4.3.1. Summary of Toxicological Doses and Endpoints for Etofenprox for Use in Dietary and NonOccupational Human Health Risk Assessments.

Exposure/ 

Scenario

Point of 

Departure

Uncertainty/F

QPA Safety 

Factors

RfD, PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological Effects

Inhalation (All 

durations)

NOAEL =

10.6 mg/kg/day

FQPA = 1x

UFA = 10x

UFH = 10x

LOC for MOE 

≤ 100

13-Week Inhalation Toxicity in Rat 

(MRID No. 40449705)

LOAEL = 52.3 mg/kg/day based on organ 

weight changes and histopathological

changes in liver, adrenals and thyroid.

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be carcinogenic to humans at doses that do not alter rat thyroid hormone 

homeostasis.” 

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). 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.

Table 4.3.2 Summary of Toxicological Doses and Endpoints for Etofenprox for Use in Occupational Human 

Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertainty 

Factors

Level of Concern 

for Risk 

Assessment

Study and Toxicological Effects

Dermal (All 

durations) N/A

No systemic toxicity was identified in the 

dermal 28-day study; Highest Dose Tested was 

1000 mg/kg/day.

Inhalation (All 

durations)

NOAEL =

10.6 

mg/kg/day

FQPA = 1x

UFA = 10x

UFH = 10x

LOC for MOE 

≤ 100

13-Week Inhalation Toxicity in Rat 

(MRID No. 40449705)

LOAEL = 52.3 mg/kg/day based on organ 

weight changes and histopathological

changes in liver, adrenals and thyroid.

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be carcinogenic to humans at doses that do not alter rat thyroid 

hormone homeostasis.” 

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). MOE = margin of exposure. LOC = level of 

concern. N/A = not applicable.

4.4 Recommendation for Combining Routes of Exposure for Risk Assessment

As per FQPA, 1996, when there are potential residential exposures to a pesticide, aggregate risk 

assessment must consider exposures from three major sources: oral, dermal and inhalation 

exposures. 

For short-, intermediate- and long-term aggregate risk assessments, the incidental oral and 

inhalation exposures can be combined due to the presence of a common toxicity endpoint 

(decreased body weight and adverse thyroid, liver and kidney effects). There is no appropriate 
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endpoint for dermal exposure risk assessment because no systemic toxicity was observed at the 

limit dose (1000 mg/kg/day) following repeated (28 days) dermal application to rabbits.

5.0 Dietary Exposure and Risk Assessment 

5.1 Residues of Concern Summary and Rationale

The nature of the residue in plants, rotational crops, and livestock is adequately understood based 

on acceptable metabolism studies conducted on rice, lettuce, grape, rapeseed, rotational crops, 

lactating goats, and laying hens (B. Cropp-Kohlligian, D342668, 07/10/2008). The HED 

Residues of Concern Knowledgebase Subcommittee (HED ROCKS Report, D352227, 

05/20/2008) has determined that the residue of concern for the tolerance expression in rice is 

etofenprox, and that the residues of concern for risk assessment are etofenprox and α-CO. 

Unlike rice, the residue distributions in grape, lettuce, and rapeseed show that the α-CO 

metabolite is present at <10% and therefore can be considered a minor metabolite. Based on the 

metabolism data from the three diverse crops of grape, lettuce, and rapeseed, the residues of 

concern for monitoring and risk assessment in plants other than rice is parent etofenprox. The 

residue of concern for tolerance expression and risk assessment in livestock commodities is 

etofenprox 

EDWCs reflect drinking water exposure to residues of concern for etofenprox, which the 

ROCKS identified as the parent compound and two of its degradates, α-CO and 4′-OH. 

Structures of the metabolites can be found in Appendix B.

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

Expression.

Matrix Residues included in Risk 

Assessment

Residues included in 

Tolerance Expression

Plants

Rice Etofenprox and α-CO Etofenprox

All Crops (Except Rice) Etofenprox Etofenprox

Rotational Crops None None

Livestock

Ruminants Etofenprox Etofenprox

Poultry Etofenprox Etofenprox

Drinking Water Etofenprox, α-CO, and 4′-OH Not Applicable

Etofenprox =1-[[2-(4-ethoxyphenyl)-2-methylpropoxy]methyl]-3-phenoxybenzene (CAS); α-CO = 2-(4-ethoxyphenyl)-2-methylpropyl-3-

phenoxybenzoate; 4′-OH = 2-(4-ethoxy-phenyl)-2-methyl-propyl-3-(4-hydroxyphenoxy)benzyl ether

5.2 Food Residue Profile

The IR-4 has submitted field trial data for etofenprox to control adult mosquitos over growing 

crops. Three field trials on alfalfa, bean foliage, grass, and leaf lettuce were conducted in the 

United States (California and Florida) during the 2010 growing season. The number and 

locations of these field trials for use of mosquito control have been accepted by HED after 

review of the residue data and discussion by HED’s ChemSAC (ChemSAC minutes, 09/29/2010

and 03/13/2013). Each trial consisted of three treated plots (one for each commodity). 
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Because the submission lacked residue data modeling the multiple proposed applications and 

applications made via ground equipment, IR-4 and EFED provided modeled estimates of the 

residues following multiple aerial and ground ULV applications of etofenprox. While the data

submitted were accepted, EFED estimated multiple applications of etofenprox as a mosquito 

adulticide over crop land using AgDisp version 8.23 and the TREX model. EFED confirmed the 

estimated residues (1.5 ppm) generated by IR-4. Aerial ULV deposition data from the residue 

study and modeling suggest that deposition values will typically be in the range of 10-33% of the 

amount of pesticide applied. EFED also modeled the residues following multiple applications 

using conservative application efficiencies of 33% and using the worst case wind speed of 1 mph

allowed on the etofenprox label. The resulting residue estimate was 4.77 ppm for aerial 

applications (C. Peck, D407817, 02/28/2013). Based on the data generated by IR-4 and EFED 

supporting multiple applications using residue data generated from one aerial application and 

best-available conservative modeling, HED concluded that a tolerance of 5.0 ppm is adequate to 

cover the expected residues from multiple ground and aerial applications (ChemSAC 

03/13/2013). 

Processing Data: No new processing data were submitted with this petition. 

Meat, Milk, Poultry and Eggs: HED has required additional tolerances on livestock commodities 

in addition to the tolerances proposed by IR-4 on food and feed commodities. The residue data 

from the cattle feeding study are adequate. The feeding study data indicate that residues of 

etofenprox are not expected to exceed 10 ppm in fat and meat byproducts, 0.60 ppm in milk, and 

0.40 in meat of cattle, goats, horses, and sheep. Residues are not expected to exceed 4.0 on fat 

and meat byproducts, and 0.20 ppm in meat of hogs. Tolerances should be proposed as listed in 

Table 2.2.2. 

A feeding study was not submitted for poultry. HED estimated tolerances on poultry 

commodities based on the results of the hen metabolism study (14-day consecutive feeding; 9.6 

ppm (maximum level)) residues are not likely to exceed 0.40 ppm in egg, 1.0 ppm in fat/skin and 

meat byproducts, and 0.01 ppm for poultry meat. Tolerances should be proposed as listed in 

Table 2.2.2. If additional uses of etofenprox with poultry feed items are proposed in the future, a 

poultry feeding study may be required.

5.3 Water Residue Profile

The drinking water residues used in the dietary risk assessment were provided by EFED in the 

following memorandum: “Drinking Water Assessment for the Etofenprox Label Amendment” 

(C. Peck, D398044, 02/07/2012) and incorporated directly into this dietary assessment. Water 

residues were incorporated in the DEEM-FCID into the food categories “water, direct, all 

sources” and “water, indirect, all sources.” 

EDWCs in surface water and in ground water (Table 5.3) were generated for the registered uses 

on rice and the proposed/amended use for vector control. As the amendment to the proposed 

label does not increase the maximum application rates, EFED recommends using the estimated 

drinking water concentrations from a drinking water assessment conducted in 2010 (G. Orrick, 
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D370749, 01/11/2010) as discussed in the 2012 drinking water assessment update (C. Peck, 

D398044, 02/07/2012). 

The drinking water models and their descriptions are available at the EPA internet site: 

http://www.epa.gov/oppefed1/models/water/.

Table 5.3. Total Residue EDWCs of Etofenprox in Surface Water and Ground Water for Current Uses Based 

on the Maximum Use Patterns, Rice and Outdoor FoggersA,B,C.

Source Use (modeled rate)

1-in-10-year 

Peak Exposure 

(μg/L)

1-in-10-year 

Annual Mean 

Exposure (μg/L)

30-year Mean 

Exposure (μg/L)

Surface water Rice & vector control

(0.45 lbs a.i./A/year)B 1.4 1.2 <1.2

Surface water Rice (0.27 lbs a.i./A/year) 1.0 1.0 <1.0

Ground water Outdoor fogger (0.52 lbs a.i./A/year) 3.0 x 10-33.0 x 10-3<3.0 x 10-3

A Proposed uses include a proposed use for mound-building ant control and a proposed label amendment for the 

current outdoor structural use.

B These EDWCs represent an upper bound on co-occurrence between use on rice and vector control use.

C Drinking Water Assessment for the Etofenprox Label Amendment (C. Peck, D398044, 02/07/2012).

5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

HED used modeled tolerance level residues for all food and livestock commodities, default 

processing factors, and estimated %CT from BEAD for all commodities. Table 2.2.2 lists all 

changes to tolerance values and HED recommended tolerances for the proposed crops used in the 

dietary assessment. 

5.4.2 Percent Crop Treated Used in Dietary Assessment

BEAD provided percent crop treated estimates for the proposed uses (PCTn) of etofenprox as a 

mosquito adulticide which result in inadvertent residues on food and feed commodities. These 

estimates represent the upper bound of use expected during the pesticide’s initial five years of 

registration; that is, PCTn for etofenprox is a threshold of use that EPA is reasonably certain will 

not be exceeded for each registered use site. The PCT recommended for use in the chronic 

dietary assessment is calculated as the average PCT of the market leader or leaders, (i.e., the 

one(s) with the greatest PCT) on that site over the three most recent years of available data. The 

Comparisons are only made among pesticides of the same pesticide type (e.g., the market leader 

for insecticides on the use site is selected for comparison with a new insecticide). The market 

leader included in the estimation may not be the same for each year since different pesticides 

may dominate at different times. Typically, EPA uses USDA National Agricultural Statistics 

Service (NASS) as the source of data because it is publicly available and directly reports values 

for PCT. When a specific use site is not reported by USDA/NASS, EPA uses proprietary data 

and calculates the PCT given reported data on acres treated and acres grown. If no data are 

available, EPA may extrapolate PCT from other crops (proxies), if the crop management and 

pest spectrum are substantially similar. A retrospective analysis to validate this approach shows

few cases where the PCT for the market leaders were exceeded. Further review of these cases 
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identified factors contributing to the exceptionally high use of a new pesticide. Given the results 

of this review, to evaluate whether the PCT for etofenprox could be exceeded, EPA considered 

whether there may be unusually high mosquito pressure or disease transmission potential; and 

whether the market leaders are well established for that use; and whether pest resistance issues 

with past market leaders provide etofenprox with significant market potential. Given currently 

available information, BEAD concludes it is unlikely that actual PCT for etofenprox will exceed 

the estimated PCT for new uses during the next five years. 

The analysis to derive the estimates was considered conservative, and used national and state 

level usage data from the most widely used mosquito insecticides. Additionally, the analysis 

assumed that all etofenprox applications will be made randomly across the landscape without 

regard to land use patterns which is a conservative assumption because mosquito adulticide 

applications are generally made to populated urban and suburban areas – not typically near 

cropland. The following maximum percent crop treated estimates (D. Brassard, D406229,

01/04/2013) were used in the chronic dietary risk assessment for the following crops: apples: 

1%; almonds: 5%; apricots: 5%; artichokes: 5%; avocados: 5%; broccoli: 5%; Brussels sprouts: 

5%; carrots: 5%; cauliflower: 5%; celery: 5%; chicory: 5%; dates: 5%; field corn: 1%; figs: 5%; 

garlic: 5%; grapes: 5%; honeydew melon: 5%; kiwifruit: 5%; lemons: 5%; nectarines: 5%; 

olives: 5%; oranges: 15%; pears: 1%; persimmons: 5%; pistachios: 5%; plums: 5%; pluots: 5%; 

pomegranates: 5%; prunes: 5%; raisins: 5%; rice: 3%; tomatoes: 5%; walnuts: 5%; and wheat: 

1%. It was assumed that all other crops (including livestock commodities, milk, and eggs) were 

3% CT based on the conservative analysis conducted by BEAD (D. Brassard, D406229, 

01/04/2013). 

5.4.3 Acute Dietary Risk Assessment

An acute dietary endpoint was not identified in the etofenprox toxicity database. Therefore, an 

acute dietary exposure assessment was not conducted.

5.4.4 Chronic Dietary Risk Assessment

The chronic dietary (food and drinking water) exposure assessment for etofenprox was 

conducted using the Dietary Exposure Evaluation Model Food Commodity Intake Database 

(DEEM-FCID) using food consumption data from the U.S. Department of Agriculture’s 

(USDA’s) National Health and Nutrition Examination Survey, What We Eat in America 

(NHANES/WWEIA). The assessment assumed modeled and/or established tolerance-level 

residues, incorporated estimated %CT values, and used DEEM default processing factors. 

EDWCs from EFED (1.2 μg/L) were also included. The results of the chronic analysis indicate 

that the chronic dietary (food and drinking water) exposure and risk does not exceed HED’s 

LOC [i.e., <100% cPAD] for the U.S. population and all population subgroups. The resulting 

chronic dietary (food and drinking water) risk estimates were 8.6% for the U.S. population, and 

32% for children 1 to <2 years old, the highest exposed population subgroup. The assumptions 

incorporated into the chronic dietary assessment are considered conservative and unlikely to 

underestimate exposure. For future uses of etofenprox, further refinement using etofenproxspecific field trial data to estimate potential residues resulting from mosquito adulticide use near 

growing food commodities would further refine the dietary and aggregate exposure assessment. 
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5.4.5 Cancer Dietary Risk Assessment

Etofenprox is classified as “Not Likely to be Carcinogenic to Humans”; therefore, a cancer 

dietary risk assessment is not required.

5.4.6 Summary Table

Table 5.4.6. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Etofenprox.

Population Subgroup

Chronic Dietary

Dietary Exposure

(mg/kg/day) % cPAD*

General U.S. Population 0.003196 8.6

All Infants (<1 year old) 0.004154 11

Children 1-2 years old* 0.011805 32

Children 3-5 years old 0.009360 25

Children 6-12 years old 0.004693 13

Youth 13-19 years old 0.002732 7.4

Adults 20-49 years old 0.002352 6.4

Adults 50-99 years old 0.002370 6.4

Females 13-49 years old 0.002327 6.3

*The subpopulation with the highest risk estimates are in bold.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

Etofenprox is currently registered on various residential use sites, such as cat and dog spot-ons, 

as a bed bug treatment, as indoor space and crack and crevice sprays, and as indoor and outdoor 

foggers. Etofenprox formulations for use in residential settings include EC, SC, aerosol, and 

fogger formulations. The existing residential uses have been reassessed in this document to

reflect updates to HED’s 2012 Residential SOPs3along with policy changes for body weight 

assumptions (B. O’Keefe, D396533, 06/25/2013). The revision of residential exposures will 

impact the human health aggregate risk assessment for etofenprox. Table 6.0 summarizes the 

existing residential uses of etofenprox and the need for an updated residential exposure 

assessment.

There are no residential handler exposures from the amended use of etofenprox as a ULV aerial 

and ground-based fogger application over crop, pasture, and range land. However, there are 

potential post-application exposures to adults and children from the ULV aerial and groundbased fogger applications in the vicinity of residential areas.

 

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Table 6.0. Proposed and Existing Use Patterns and the Need for Re-Assessment.

Use Rate

Residential 

Handler 

Assessment

Needed?

Residential Post-Application Assessment Needed?

Adults Children

Inhalation Inhalation Incidental Oral

Proposed/Amended Use

Mosquito 

Adulticide

0.007 lb 

ai/A No Yes Yes Yes 

Existing Uses

Indoor Surfacedirected Spray 

(Spot & C/C)

0.048 lb 

ai/gal Yes Yes Yes( Yes

Indoor Aerosol 

Surface-directed 

Spray 

(Broadcast)

0.01 lb 

ai/can Yes Yes Yes Yes

Indoor Aerosol 

Surface-directed 

Spray (bed 

bug/spot)

0.01 lb 

ai/can Yes Yes Yes Yes

Indoor Aerosol 

Space Spray

0.01 lb 

ai/can Yes Yes Yes Yes

Indoor Fogger 6 oz, 1%, 

2.4 μg/cm2 No Yes Yes Yes

Outdoor Fogger 0.0055 lb 

ai/day Yes No (negligible) Yes Yes (residues deposit on turf)

Pet (spot-on) 0.385 g/cat

1.95 g/dog No (negligible) No (negligible) No (negligible) Yes

* No systemic toxicity was identified in the dermal 28-day study; Highest Dose Tested was 1000 mg/kg/day; therefore a dermal 

exposure assessment is not required for etofenprox.

6.1 Residential Handler Exposure

Residential handler exposure and risks from the currently registered indoor and outdoor uses of 

etofenprox were reassessed to reflect updates to the 2012 HED Residential SOPs4. 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; however, there are some 

instances where longer-term exposures are possible (e.g., pet care uses and indoor uses). 

Residential handlers are assumed to be wearing short-sleeved shirts, short pants, shoes, and socks 

during etofenprox application. Because there was no dermal endpoint chosen for etofenprox, 

risk was assessed only for exposure via the inhalation route. Although PODs from an oral study 

were used to assess residential handler inhalation risks to etofenprox, HED does not believe this 

assessment is under protective of adult handlers because of etofenprox’s physical chemical 

properties and low acute inhalation toxicity. 

HED’s LOC for the MOE is defined by the uncertainty factors that are applied to the assessment. 

HED applies a 10X factor to account for variability among species and a 10X factor to account 

for variability within species. The total uncertainty factor that has been applied to the non-cancer 

assessment of etofenprox is 100X for residential exposure. Residential exposure and risk 

resulting in MOEs greater than or equal to 100 will not be of concern to HED (LOC = 100). 

 

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Short-term residential handler inhalation MOEs were not of concern to HED, and ranged from 

28,000 to 110,000 and are shown in Appendix D. 

6.2 Post-Application Exposure

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

environment that has been previously treated with etofenprox. Because of the registered indoor 

uses, intermediate-term post application exposures are possible. However, since the short- and 

intermediate-term endpoints and PODs for inhalation and oral routes are the same, the short-term

exposure and risk estimates are considered to be protective of potential intermediate-term 

exposure and risk. Because dermal toxicity endpoints were not identified for etofenprox, only 

short- and intermediate-term post-application inhalation exposures were assessed for adults and 

short- and intermediate-term post-application inhalation and incidental oral exposures were 

assessed for children. Additionally, long-term post-application incidental oral exposures to 

children from petting treated cats or dogs were also assessed. 

Chemical-specific exposure data for use of etofenprox as a mosquito adulticide have not been 

submitted; therefore, the 2012 Residential SOPs5and the AGDRIFT model were used to estimate 

exposures following etofenprox use as a mosquito adulticide. To calculate airborne 

concentrations from aerial ULV applications, HED used AGDISP modeling software, version 

8.26. AGDISP predicts the motion of spray material released from aircraft, including the mean 

position of the material and the position variance about the mean as a result of turbulent 

fluctuations. The model was initially developed by the National Aeronautics and Space 

Administration, the USDA Forest Service, and the U.S. Army, with contracting oversight 

provided by Robert B. Ekbiad and John H. Barry. This version of AGDISP includes additional 

features developed for the USDA Forest Service and the National Council for Air and Stream 

Improvement, through oversight provided by Harold W. Thistle and George G. Ice, respectively.

AGDISP is capable of producing a variety of useful outputs. The key for HED in this assessment 

was to determine from the model what amount of the application volume remained aloft and 

what amount of the resulting droplets deposited on the surfaces in the treatment area as well as 

downwind from the treatment area. The model allows for the estimation of air concentrations in 

the breathing zones of adults and toddlers, as well as residues depositing on turf for use in 

calculating the risks to individuals residing in areas being treated by aerial application of 

etofenprox. 

A discussion of the assumptions and models used to assess the proposed/amended use of 

etofenprox in residential settings can be found in the occupational and residential exposure 

assessment (B. O’Keefe, D396533, 04/12/2013). 

Because of the registered indoor uses, intermediate-term post application exposures are possible. 

However, since the short- and intermediate-term endpoints and PODs for inhalation and oral 

routes are the same, the short-term exposure and risk estimates are considered to be protective of 

potential intermediate-term exposure and risk.

 

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For children 1 to <2 years old, short-term post-application inhalation MOEs range from 630 to 

580,000. For adults, short-term post-application inhalation MOEs range from 2,300 to 

2,500,000. For children 1 to <2 years old, short-term post-application incidental oral MOEs for 

all residential exposure scenarios range from 750 to 260,000,000. 

Long-term exposure is expected from the use of etofenprox on treated pets. Children and adults 

may be exposed over a longer duration because pets may be treated continuously throughout the 

year. For adults, there was no dermal hazard identified for etofenprox, and post-application 

inhalation exposure is considered negligible from treating companion animals. For children 1 to 

<2 years old, long-term incidental oral exposures are expected from contact with treated pets. 

The long-term incidental oral MOEs range from 410 to 1,000 for children 1 to <2 years old. All 

residential exposure estimates are not of concern to HED and can be found in Appendix D.

6.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)

Combined Residential Exposures and Risks from Existing Uses

Residential exposure scenarios should be combined whenever there is a reasonable probability of 

occurrence on a single day and the pest that is being controlled is the same. HED combines 

exposures for treatments to control the same pests (e.g. flea treatment on surfaces and on pets) 

because such treatments could reasonably be expected to occur on the same day. However, HED 

does not combine exposures for treatment of different pests (e.g. flying insects and fleas) because 

the probability of co-occurrence on the same day would be considered extremely low.

Additionally, for etofenprox different end use products are registered to treat for fleas as for 

flying insects, so the likelihood that someone would use two different products containing 

etofenprox on the same day would be low.

It is probable that treatment for fleas on pets (dogs or cats) and indoor surfaces with etofenprox 

could co-occur on the same day from the existing registered uses of etofenprox. Indoor surfaces 

can be treated for fleas with several etofenprox products; i.e., liquid crack and crevice sprays, 

aerosol sprays, or indoor foggers. Hand-to-mouth incidental oral exposure from contact with

treated carpets following aerosol sprays of etofenprox to treat fleas resulted in the highest 

estimated incidental oral exposure for children 1 to <2 years old; i.e., 0.0265 mg/kg/day (MOE = 

750). The hand-to-mouth exposure from contact with treated carpets was then combined with 

hand-to-mouth exposures from contact with treated pets (small dogs) for children 1 to <2 years 

and resulted in an exposure estimate of 0.0356 mg/kg/day and an MOE of 560. These combined 

incidental oral exposures were then combined with post-application inhalation exposure resulting 

from inhalation of the aerosol spray. The combined post-application incidental oral and 

inhalation MOE for children 1 to <2 years from etofenprox treatment for fleas is 560, and not of 

concern to HED. 

However, the most conservative combined post-application exposure estimate for children 1 to 

<2 years results from the use of etofenprox as an indoor treatment for flying insects. Inhalation 

exposure following treatment for flying insects with an aerosol spray resulted in an MOE of 630

(dose = 0.0170 mg/kg/day). Hand-to-mouth exposure to treated carpet following the use of an 

aerosol spray resulted in an MOE of 5,600 (dose = 0.0036 mg/kg/day). Both the air and the 
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carpet may contain residues following an aerosol spray indoors, so HED combined hand-tomouth exposure from treated indoor surfaces with inhalation exposure following indoor aerosol 

sprays. The combination of exposure from resulted in a combined MOE of 570, which is not of 

concern to HED. 

Table 6.3.1. Short- and Intermediate-Term Residential Combined (Multiple Exposure Scenarios) Non-Cancer Exposure and Risk 

Estimates for Etofenprox.

Combined 

Exposure 

Scenario

Lifestage Exposure Scenario Route of Exposure Dose (mg/kg/day) Individual MOE Combined 

Total MOE

Treatment for 

Flying Insects

Children (1-

<2 years)

Exposure through air Inhalation 0.0170 630

570 Indoor Carpet from 

Aerosol Spray

Hand-to-Mouth

(Carpet) 0.0036 5,600

Treatment for 

Fleas

Indoor Carpet from 

Aerosol Spray

Inhalation 0.000118 580,000

Hand-to-Mouth 0.0265 560

560

Pet (Dog) Spot-on Hand-to-Mouth 0.0091

Combined Residential Exposures and Risks from Use as a Mosquito Adulticide

It is probable that post-application inhalation and incidental oral exposures could co-occur on the 

same day from the amended/proposed uses of etofenprox as a mosquito adulticide. There are no 

concurrent adult exposures to combine. Risk estimates are calculated using the Total MOE

approach because, while inhalation and incidental oral endpoint effects are the same, they occur 

at different dose levels. The combined oral and inhalation exposures to children 1 to <2 years 

old following both ground and aerial etofenprox public health mosquito control treatments are 

not of concern to HED. It is important to note that the conservative assumptions listed for the 

individual routes of exposure are combined here, leading to an upper-bound estimate of 

combined risks. An example of the conservative nature of the estimate of combined exposures 

following truck-fogger application is the fact that the inhalation exposure (based on the full 

maximum application rate with a dilution factor of 1 to 100) is combined with the incidental 

ingestion exposure from residues depositing on the turf (based on an estimated deposition rate 

based on the full application rate). This approach may result in double-counting some of the 

residue levels estimated for ground-based etofenprox applications.

Table 6.3.2. Combined Inhalation and Incidental Oral Exposure and Risk Estimates for Children 1 to <2 

years Old from Mosquito Adulticide Use.

Post-application 

Exposure Scenario

Inhalation 

Dose 

(mg/kg/day)

Inhalation 

MOE1

Incidental Oral

Hand-to-Mouth 

Dose (mg/kg/day)

Incidental 

Oral MOE1

Total 

Combined 

MOE2

From Ground ULV 0.0000762 140,0000 0.0000352 570,000 110,000

From Aerial ULV 0.0000297 360,000 0.0000352 570,000 220,000

1. MOE = NOAEL/ADD, where NOAEL (inhalation) = 10.6 mg/kg/day, with an LOC of 100 and NOAEL (incidental oral) = 20 

mg/kg/day, with an LOC of 100.

2. Total MOE = 1/[ (1/MOEinhal) + (1/MOEincid oral)]. MOEs greater than or equal to 100 are not of concern to HED.

6.4 Residential Risk Estimates for Use in Aggregate Assessment

For the purpose of the etofenprox aggregate human health risk assessment, a summary of the 

most conservative exposure estimates from all residential uses of etofenprox are provided in 
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Table 6.4. The bolded scenarios represent the recommended residential scenarios for inclusion 

in the aggregate human health risk assessment for etofenprox.

Table 6.4. Recommendations for the Residential Exposures for the Etofenprox Aggregate Assessment.1

Lifestage

Residential Handler Residential Post-application 

Dose 

(mg/kg/day)2 MOE3 Dose (mg/kg/day)4 MOE5

Inhalation Inhalation Inhalation Oral Total Inhalation Oral Total

Short- and Intermediate-Term

Adult (Aerosol spray can for 

flying insects) 0.000375 28,000 0.00462 N/A N/A 2,300 N/A N/A

Children 1 to <2 years

(Treatment for flying insects) N/A 0.0170 0.0036 0.0206 630 5,600 570

Long-Term

Children 1 to<2 years

(Incidental oral exposure to 

treated (small) dogs)

N/A N/A 0.0091 N/A N/A 410 N/A

1 Bolded risk estimates should contribute to the residential exposure portion of the aggregate assessment. 

2 Residential Handler Dose = the highest handler dose for each applicable lifestage of all scenarios assessed from Table E4.

3 Residential Handler MOE = the MOEs associated with the highest doses identified in D1.

4 Residential Post-application Dose = the highest post-application dose for each applicable lifestage of all scenarios assessed from Table 6.3.1. 

Total = inhalation + incidental oral, where applicable.

5 Residential Post-application MOE = the MOEs associated with the highest doses identified in Table 5.2.1. Total = 1 ÷ [(1/Inhalation MOE) + 

(1/Incidental oral MOE)]. 

6.5 Residential Bystander Post-application Inhalation Exposure

Based on the Agency's current practices, a quantitative post-application inhalation exposure 

assessment was not performed for etofenprox at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV), low vapor pressure (2.5x10-8 mm Hg at 25 oC), and 

the low proposed use rate (0.007 lb ai/A). 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, 20106. 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 etofenprox.

6.6 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 etofenprox. 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 information at 

http://www.epa.gov/opp00001/factsheets/spraydrift.htm). On a chemical by chemical basis, the 

 

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Agency is now requiring interim mitigation measures for aerial applications that must be placed 

on product labels/labeling. The Agency has completed its evaluation of the new database 

submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is 

developing a policy on how to appropriately apply the data and the AgDRIFT computer model to 

its risk assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. 

After the policy is in place, the Agency may impose further refinements in spray drift 

management practices to reduce off-target drift with specific products with significant risks 

associated with drift.

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. For etofenprox, potential exposures from food, drinking water, and 

residential scenarios were aggregated. The aggregate assessment considers changes to the 2012 

Residential SOPs. HED confirms that there are no exposure risks of concern resulting from 

etofenprox use as a mosquito adulticide over or near growing food commodities. 

7.1 Acute Aggregate Risk

No adverse effects attributable to a single dose were observed in oral toxicity studies, including 

developmental toxicity studies in rats and rabbits. Therefore, an acute reference dose was not 

established and an acute aggregate risk assessment was not conducted. 

7.2 Short- and Intermediate-Term Aggregate Risk

There is potential short-term exposure to etofenprox via dietary (which is considered background 

exposure) and residential (which is considered primary) exposure pathways. For adults, these 

pathways lead to exposure via oral (background) as well as dermal and inhalation (primary) 

routes. The most conservative scenario was chosen for each population. For a description of the 

residential exposure scenarios considered in the aggregate assessment, see Section 6.4. 

The aggregate MOE for adults, including post-application inhalation exposure from aerosol 

sprays is 1,700 and is not of concern to HED. The aggregate MOE for children 1 to <2 years

old, including post-application incidental oral and post-application inhalation exposures from 

using etofenprox in residential settings is 420 and is not of concern to HED. 

Further refinement using chemical-specific field trial data to estimate potential residues resulting 

from mosquito adulticide use near growing food commodities would further refine the dietary 

and aggregate exposure assessment. 

Table 7.2. Short- and Intermediate-Term Aggregate Risk Calculations.

Population Short-Term Scenario
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LOC for 

Aggregate Risk1

Dietary

MOE2

MOE Oral 

Residential 

Exposure3

MOE 

Inhalation 

Residential 

Exposure4

Aggregate 

MOE (food, 

water, and 

residential)5

Adults 100 6,300 N/A 2,300 1,700

Children 1 to <2 

years old 100 1,700 5,600 630 420

1

10X for interspecies extrapolation and 10X for intraspecies variation.

2 Adult dietary MOE = [short- and intermediate-term oral NOAEL (20 mg/kg/day)/chronic dietary exposure

(0.003196 mg/kg/day)]. Children 1-2 years old dietary MOE = [short- and intermediate-term oral NOAEL (20 

mg/kg/day)/chronic dietary exposure (0.011805 mg/kg/day)]. See Table 5.4.6 for dietary exposure estimates.

3 Children 1-2 years old incidental oral MOE = [(short- and intermediate-term incidental oral NOAEL (20 

mg/kg/day)/hand-to-mouth residential exposure (0.0036 mg/kg/day)]. Residential exposure values can be found in 

Table 6.4. 

4 Adult inhalation MOE = [short-term inhalation NOAEL (10.6 mg/kg/day)/high end inhalation residential inhalation 

exposure (0.0046 mg/kg/day)]. Children 1-2 years old inhalation MOE = [short-term inhalation NOAEL (10.6 

mg/kg/day)/high end inhalation residential inhalation exposure (0.0170 mg/kg/day)]. Residential exposure values 

can be found in Table 6.4. 

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

7.3 Chronic Aggregate Risk

There is potential chronic/long-term exposure to etofenprox via dietary (which is considered 

background exposure) and residential (which is considered primary) exposure pathways for 

children 1 to <2 years old. For a description of the residential exposure scenarios considered in 

the aggregate assessment, see Section 6.4. 

Chronic/long-term exposure to etofenprox for adults is expected via the dietary (background 

exposure) and residential (primary) exposure pathways; however, there is no dermal hazard 

identified for etofenprox, incidental oral exposure is not expected for adults, and inhalation 

exposure is not expected for adults from treating pets; therefore an adult chronic residential 

exposure assessment was not conducted. Chronic aggregate exposure is considered equivalent to 

dietary exposure for adults (See Section 5.4.6). 

The aggregate MOE for children 1 to <2 years old, including incidental oral exposures from 

contact with treated pets is 180 and is not of concern to HED. 

Further refinement using chemical-specific field trial data to estimate potential residues resulting 

from mosquito adulticide use near growing food commodities would further refine the dietary 

and aggregate exposure assessment. 
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Table 7.3. Long-Term/Chronic Aggregate Risk Calculations.

Population

Long-Term/Chronic Scenario

LOC for Aggregate 

Risk1

Dietary

MOE2

MOE Oral 

Residential 

Exposure3

Aggregate MOE 

(food, water, and 

residential)4

Children 1-2 years old 100 310 407 180

1

10X for interspecies extrapolation and 10X for intraspecies variation.

2 MOE dietary = [chronic oral NOAEL (3.7 mg/kg/day)/chronic dietary exposure (0.003196 mg/kg)]. The dietary 

exposure value is found in Table 5.4.6 (children 1-2 years old).

3 MOE oral = [chronic oral NOAEL (3.7 mg/kg/day)/hand-to-mouth residential exposure from treated small dogs

(0.0091 mg/kg/day)]. The residential exposure value can be found in Table 6.4. 

4 MOE Aggregate = 1/[(1/MOE dietary) + (1/MOE oral) 

8.0 Cumulative Exposure/Risk Characterization

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 etofenprox and any other substances and etofenprox does not appear to produce a toxic 

metabolite produced by 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 etofenprox. Although etofenprox shares some 

structural characteristics with synthetic pyrethroids, it is not included in the pyrethroid 

cumulative assessment. 

Naturally occurring pyrethrins and the synthetic pyrethroids (collectively called ‘pyrethroids’) 

are grouped for purposes of cumulative risk assessed based on the following shared 

characteristics: 1) Common structure - Pyrethrins and pyrethroids share a common structure; 

acid and alcohol moieties joined through an ether linkage; 2) Sodium channel disruption - In 

vitro studies demonstrate the ability of pyrethroids to modify mammalian sodium channel 

kinetics, leading to alterations in membrane excitability and firing potentials; 3) Neurotoxic 

Effects - Pyrethroid toxicity is manifested through neurological syndromes described as either T 

(fine tremors), CS (choreoathetosis and salivation), or some combination thereof, depending on 

the structure. Open literature supports a correlation between the modification in sodium channel 

kinetics and the resulting syndrome.

Etofenprox is not included in the pyrethroid common mechanism grouping or included in the 

cumulative risk assessment because etofenprox does exhibit these key characteristics. 

Etofenprox is an ether compound; pyrethroids are esters. Etofenprox exposure does not result in 

the neurotoxic syndromes typical of pyrethroids and no available data suggest the molecular 

target for etofenprox is the sodium channel.

For the purposes of this tolerance action, therefore, EPA has not assumed that etofenprox has a 

common mechanism of toxicity with other pyrethroids. 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 
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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

HED has evaluated occupational exposure from the proposed/amended uses of etofenprox as a 

mosquito adulticide on or near agricultural crops. 

9.1 Short-/Intermediate-Term Handler Risk

Etofenprox is currently registered for use as a public health mosquito adulticide, except for over 

crop land and may only be applied only by federal, state, tribal, or local government officials 

responsible for public health or vector control using ULV aerial equipment, ULV backpack 

sprayers, truck mounted thermal ground foggers, or handheld thermal foggers. However, IR-4 

has proposed to remove the restriction over cropland, necessitating an evaluation of occupational 

handler risk from use of etofenprox as a mosquito adulticide near and over crop areas. 

Application methods, maximum application rates, and use sites are summarized in Table 3.3. 

Based on the amended use pattern, there is a potential for short- and intermediate-term 

occupational exposure to etofenprox during handling (mixing, loading, and applying) and postapplication activities. However, since the same endpoint and POD were selected for short- and 

intermediate-term durations, short-term exposure and risk estimates are considered to be 

protective of intermediate-term exposure and risk. Additionally, a dermal toxicity endpoint was 

not identified for etofenprox, so only inhalation exposures were assessed for occupational 

handlers. The proposed labels do not list required personal protective equipment (PPE) or a 

proposed restricted entry interval (REI). 

HED’s LOC for the MOE is defined by the uncertainty factors that are applied to the assessment. 

HED applies a 10X factor to account for variability among species and a 10X factor to account 

for variability within species. The total uncertainty factor that has been applied to the handler 

inhalation assessment of etofenprox is 100X for occupational exposure. Occupational exposure 

and risk resulting in MOEs greater than or equal to 100 will not be of concern to HED. 

A summary of the short-term inhalation risks for occupational handlers applying etofenprox is 

provided in Table 9.1. The results of the short-term inhalation occupational handler exposure 

and risk assessment indicate that the MOEs are not of concern to HED with baseline attire (no 

respirator); the inhalation MOEs for all handler scenarios for etofenprox mosquito adulticide

applications ranged from 8,600 to 240,000. 

Table 9.1. Occupational Handler Inhalation Exposure and Risk Estimates for Etofenprox.

Scenario

Application 

Rate1

(lb ai/acre)

Unit 

Exposure2

(mg/lb ai)

Units 

Treated3

(acres/day)

Average 

Daily Dose4

(mg/kg/day)

Short- and 

Intermediateterm MOE5

Mixer/Loader – Liquids (ULV) Open Loading 

for Aerial Application 0.007 0.000219 7500 0.000144 74,000

Mixer/Loader – Liquids (ULV) Open Loading 

for Truck-Mounted Ground Fogging 0.007 0.000219 3000 0.0000575 180,000

Applicator – Aerial Liquids (ULV 0.007 0.000068 7500 0.0000446 240,000
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Table 9.1. Occupational Handler Inhalation Exposure and Risk Estimates for Etofenprox.

Scenario

Application 

Rate1

(lb ai/acre)

Unit 

Exposure2

(mg/lb ai)

Units 

Treated3

(acres/day)

Average 

Daily Dose4

(mg/kg/day)

Short- and 

Intermediateterm MOE5

Applicator – Truck-Mounted Ground-Fogger 

(Airblast used as Surrogate) 0.007 0.00471 3000 0.00124 8,600

1 Maximum Application Rate.

2 Unit Exposure = mg ai/lb ai handled from the Pesticide Handler Exposure Database (PHED) or the Agricultural Handlers Exposure Task Force 

(AHETF).

3 Units Treated taken from Science Advisory Council for Exposure, Standard Operating Procedure 9.1, Standard Values for Daily Acres Treated 

in Agriculture, Rev. 25 SEP 2001.

4 Average Daily Dose (ADD) = Unit Exposure * Application Rate * Units Treated Body Weight (80 kg).

5 Margin Of Exposure (MOE) = NOAEL (mg/kg/day) ADD (mg/kg/day); where the NOAEL = 10.6 mg/kg/day for all durations of inhalation 

exposure.

9.2 Short-/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. For 

the proposed mosquito adulticide use, workers are not expected to reenter treated areas following 

application, and therefore, no quantitative assessment is required.

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 etofenprox at this time primarily because of the low acute 

inhalation toxicity (Toxicity Category IV), low vapor pressure (2.5x10-8 mm Hg at 25 oC), and 

the low proposed use rate (0.007 lb ai/A). However, there are multiple potential sources of postapplication 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, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report as well as available post-application inhalation exposure 

data generated by the Agricultural Reentry Task Force 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 etofenprox.

10.0 References
Etofenprox Human Health Risk Assessment DP No. D405380

Page 33 of 46

B. O’Keefe, D396533, 06/25/13: Etofenprox: Occupational and Residential Exposure 

Assessment for a Proposed Section 3 Use as a ULV Mosquito Adulticide. 

K. Rury, D396534, 04/16/2013: Etofenrpox: Chronic Aggregate Dietary (Food and Drinking 

Water) Exposure and Risk Assessment for the Section 3 Registration Action – Mosquito 

Adulticide over Crop Land.

M. Neggusie, D396053, 03/14/2013: Etofenprox: Public Health – Mosquito Control. Label 

Amendment to Remove Application Restriction to Cropland and Pastureland. Summary of 

Analytical Chemistry and Residue Data. 

C. Peck, D398044 and D396054, 02/07/2012: Drinking Water Assessment for the Etofenprox 

Label Amendment. 

C. Peck. D407817, 03/28/2013: Spray Drift Analysis for the Etofenprox Label Amendment. 

D. Brassard, D406229, 01/04/2013: BEAD Estimate of the Percent Crop Treated for New Use 

(PCTn) of Etofenprox when used as a Mosquito Adulticide in Agricultural Areas. 
Etofenprox Human Health Risk Assessment DP No. D405380

Page 34 of 46

Appendix A. Toxicology Profile and Executive Summaries

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for food uses of etofenprox are in Table 1. Use of the new guideline numbers 

does not imply that the new (1998) guideline protocols were used.

Study

Technical

Required Satisfied

870.1100 Acute Oral Toxicity.......................................................

870.1200 Acute Dermal Toxicity ..................................................

870.1300 Acute Inhalation Toxicity..............................................

870.2400 Acute Eye Irritation .......................................................

870.2500 Acute Dermal Irritation .................................................

870.2600 Skin Sensitization ..........................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)...............................................

870.3150 Oral Subchronic (nonrodent) .........................................

870.3200 21/28-Day Dermal .........................................................

870.3250 90-Day Dermal ..............................................................

870.3465 90-Day Inhalation..........................................................

yes

yes

yes

no

yes

yes

yes

yes

−

yes

870.3700a Developmental Toxicity (rodent)...................................

870.3700b Developmental Toxicity (nonrodent).............................

870.3800 Reproduction .................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent) ..............................................

870.4100b Chronic Toxicity (nonrodent)........................................

870.4200a Oncogenicity (rat)..........................................................

870.4200b Oncogenicity (mouse)....................................................

870.4300 Chronic/Oncogenicity (rat)............................................

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—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen) .....................................

870.6100b 90-Day Neurotoxicity (hen)...........................................

870.6200a Acute Neurotox. Screening Battery (rat) .......................

870.6200b 90-Day Neuro. Screening Battery (rat)..........................

870.6300 Develop. Neuro..............................................................

no

no

yes

yes

yes

-

-

yes

yes

yes

870.7485 General Metabolism ......................................................

870.7600 Dermal Penetration ........................................................

870.7800 Immunotoxicity

yes

yes

yes

yes

yes

yes
Etofenprox Human Health Risk Assessment DP No. D405380

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A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile

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

870.1000 Acute Oral - Dog 40449724 LD50 ≥ 5000 mg/kg IV

870.1200 Acute Dermal- Rabbit 40237710 LD50 ≥ 2100 mg/kg III

870.1300 Acute Inhalation - Rat 40237705 LC50 ≥ 5.9 mg/L IV

870.2400 Primary Eye Irritation -Rabbit 40237706

PIS for Conjunctival 

redness/edema at 24 

hrs < 0.8; at 72 hrs = 

0; reversible

IV

870.2500 Primary Dermal Irritation - Rabbit 40237707 PIS = 0.1 to 0.5, 

minimal irritation IV

870.2600 Dermal Sensitization - Guinea Pig 40237708 Negative NA

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. Study Type MRID No. (Date)/Classification/ Doses Results

870.3100 

(82-1) 

Subchronic oral 

toxicity study in 

mice.

40449702 (1982)

Acceptable/Guideline

0, 50, 500, 3000, and 15000 ppm

M: 0, 6.1, 60, 375, 1975 

mg/kg/day

F: 0, 6.9, 71, 390, 2192 

mg/kg/day)

NOAEL = M = 60, F =71 mg/kg/day.

LOAEL = M = 375, F= 390 mg/kg/day; based on clinical 

effects (increased blood urea nitrogen) and effects on 

hematology (red blood cell count, hemoglobin, and 

hematocrit).

870.3100

(82-1)

Subchronic oral 

toxicity study in 

rats.

40449703 (1986)

Acceptable/Guideline

0, 50, 300, 1800, 10800 ppm

M: 0, 3.3, 20, 120, 734 

mg/kg/day;

F: 0, 3.8, 23, 142, 820 

mg/kg/day

NOAEL = M = 20, F =23 mg/kg/day.

LOAEL = M = 120, F = 142 mg/kg/day; based on decreased 

body weight gain, increased weights of the liver and thyroid, 

and histopathological changes in the liver and thyroid, 

changes in hematology and clinical chemistry.

870.3200

(82-2)

28-day dermal 

toxicity study in 

rabbits.

45186501 (1999)

Acceptable/Guideline

0, 400, 650, 1000 mg/kg/day

Systemic NOAEL >1000 mg/kg/day.

Systemic LOAEL = not identified.

No dermal NOAEL was identified.

Dermal LOAEL = 400 mg/kg/day based on an increased 

incidence of dermal observations (scabbing, crusting, 

desquamation, exfoliation) and histopathological changes 

(diffuse epidermal hyperplasia) in both sexes of rabbits.

870.3200

(82-2)

21-day dermal 

toxicity study in 

rabbits.

40449704 (1987)

Unacceptable/Guideline

0, 2140 mg/kg/day

Unacceptable because only one 

dose used, and purity of test 

article not stated.

Systemic NOAEL = not identified.

Systemic LOAEL = 2140 mg/kg/day based on systemic 

effects on hematology (body weight, clinical signs, platelet 

counts, and thromboplastin time starting at day 8).

No dermal NOAEL was identified.

Dermal LOAEL < 2140 mg/kg/day based dermal irritation 

(slight to well-defined erythma, dermatitis,and 

hyperkeratosis).

870.3456

(82-4)

Subchronic 

inhalation- toxicity 

study in rats.

40449705 (1985)

Acceptable/Guideline

0, 0.04, 0.20, and 1.00 mg/L

NOAEL = 0.04 mg/L (10.6 mg/kg/day).

LOAEL = 0.20 mg/L (52.3 mg/kg/day); based on organ

weights and histopathology of the liver, adrenals, and thyroid.
Etofenprox Human Health Risk Assessment DP No. D405380

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. Study Type MRID No. (Date)/Classification/ Doses Results

None

4-week Thyroid 

and liver function 

oral toxicity study 

in rats.

46062302 (2004)

Acceptable/Non-Guideline

0, 1250, 5000, 20,000 ppm

M: 0, 81.2-105.6, 316.0-421.9, 

1331.6-1868.3 mg/kg/day;

F: 0, 90.2-110.3, 380.0-437.2, 

and 1520.0-1723.0 mg/kg/day)

At 2 weeks, TSH was elevated in male and female rats at the 

high dose (437% and 621%, respectively) and elevated in 

females in both the mid- and high-dose groups following 4 

weeks (321 and 586%, respectively). This effect was 

reversible in the recovery periods. T4 was depressed in male 

rats (by 34%) at the high dose at 2 weeks, levels appeared 

unaffected in female rats. T3 was unaffected by treatment in 

either sex. Thyroid peroxidase activity was largely unaffected 

by treatment. Cell proliferation in the thyroid was increased 

in high-dose males at both 2 and 4 weeks (139 and 172%), but 

was depressed in female rats at this dose.

At 2 weeks, in both sexes, increased hepatic UDPGT activity 

as measured by 4-MUGT and PNPGT (155-251%), and 

increased liver weights by 124-138% (absolute) and 133-

154% (relative). Cell proliferation was not observed in the 

liver, but incidences of centrilobular hypertrophy and 

multinucleated hepatocytes was observed in the high-dose.

870.3700

(83-3b)

Developmental 

toxicity in rabbits.

45210602 (2000)

Acceptable/ Guideline

0, 30, 100, 300 mg/kg/day

Maternal NOAEL = 100 mg/kg/day.

Maternal LOAEL = 300 mg/kg/day, based on abortions (Day 

#26-28), reduced body weights, body weight gains, and food 

consumption.

Developmental NOAEL = 100 mg/kg/day.

Developmental LOAEL = 300 mg/kg/day; based on increased 

post-implantation loss, and decreased fetal weights.

870.3700

(83-3) Developmental 

toxicity / 1-

generation 

reproduction study 

in rats.

40449711 (1985)

Acceptable/ Guideline

0, 12.5, 250, 5000 mg/kg/day

Maternal NOAEL = 250 mg/kg/day.

Maternal LOAEL = 5000 mg/kg/day, based on clinical signs 

(skin scabbing and ano-genital staining).

Developmental NOAEL = 5000 mg/kg/day.

Developmental LOAEL not identified.

Offspring NOAEL = 5000 mg/kg/day.

Offspring LOAEL not identified.

870.3800

(83-4)

2-Generation 

reproduction study 

in rats.

40449713 (1985)

Acceptable/ Guideline /

0, 100, 700, 4900 ppm

(0, 5, 35, 245 mg/kg/day)

Parental systemic NOAEL = 700 ppm (35 mg/kg/day).

Parental systemic LOAEL = 4900 ppm (245 mg/kg/day), 

based on increased organ weights of liver, thyroid, kidney and 

pathological changes in kidney.

Offspring systemic NOAEL is 700 ppm (35 mg/kg/day).

Offspring systemic LOAEL = 4900 ppm (245 mg/kg/day), 

based on increased thyroid, liver, kidney weights and 

histopathological changes in the liver and thyroid in offspring.

Reproductive NOAEL 4900 ppm (245 mg/kg/day).

No effects were noted on reproductive parameters.

870.4100

(83-1b) 

Chronic oral 

toxicity study in 

dogs.

40449706 (1985)

Acceptable/ Guideline

0, 100, 1000, 10000 ppm

M: 0, 3.46, 33.47, 351.73 

mg/kg/day

F: 0, 3.17, 32.19, and 339.12 

mg/kg/day)

NOAEL: M = 33.47, F = 32.19 mg/kg/day.

LOAEL: M = 351.73, F = 339.12 mg/kg/day; based on 

hematological parameters (decreased hematocrit, hemoglobin, 

red blood cell count, and increased platelets and prothrombin 

time), liver and kidney weights, and gross pathology of liver.

870.4200

(83-2) 

Carcinogenicity 

study in mice.

40449709 (1986)

Acceptable/ Guideline

0, 30, 100, 700, 4900 ppm

M: 0, 3.1 10.4, 75.2, 546.9 

mg/kg/day

F: 0, 3.6, 11.7, 80.9, 615.5 

mg/kg/day)

NOAEL = M = 3.1, F = 11.7 mg/kg/day.

LOAEL = M = 10.4 mg/kg/day; based on increased mortality 

and decreased body weight gain. LOAEL F = 80.9 

mg/kg/day; based on increased incidence of dilated/basophilic 

renal cortical tubules.
Etofenprox Human Health Risk Assessment DP No. D405380

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. Study Type MRID No. (Date)/Classification/ Doses Results

870.4300 

(83-5)

Combined chronic/ 

carcinogenicity 

study in rats.

40449707 (1986)

Acceptable/ Guideline

0, 30, 100, 700, and 4900 ppm 

M: 0, 1.1, 3.7, 25.5, 186.7 

mg/kg/day

F: 0, 1.4, 4.8, 34.3, 249.1 

mg/kg/day)

NOAEL = M = 3.7, F = 34.3 mg/kg/day.

LOAEL = M = 25.5 mg/kg/day; based on increased thyroid 

weight.

LOAEL = F = 249.1 mg/kg/day; based on increased liver 

weights and histopathological changes in liver and thyroid.

870.5100 

(84-2 a) Mutagenic 

potential of 

Salmonella

typhimurium and 

E. Coli.

40449715 (1985)

Acceptable/Guideline 

Salmonella strains TA 1534, 

TA97A, TA98, TAI 00, 

TA1535, TA102, & E. Coli

strain WP 2 uvrA. Conc.: 50, 

158, 500, 1582 and 5000 

μg/plate, + - S-9.

Negative. Results were negative with all 7 tester (5 S. 

typhimurium & 2 E. coli) strains up to a concentration of 500 

ug/plate both with and without S-9. The highest concentration 

was slightly toxic in some of the tester strains without the 

presence of S-9. Positive controls were adequate.

870.5100 

(84-2 a) 

Reverse mutation 

in Salmonella

typimurium.

40449716 (1985)

Acceptable/Guideline

Salmonella strains TA98, 

TA100, TA1 535, TA1 537 and 

TA1538 +- S-9. Conc.: 200, 

400, 800, and 1600, 3160, 

10,000 μg/plate, + - S-9.

Negative. Results were negative with all 5 tester S. 

typhimurium strains up to a concentration of 3200 ug/plate, at 

which slight toxicity and precipitate was observed. Positive 

controls were adequate.

870.5300 

(84-2) Gene mutation in 

Hamster (Chinese).

40449714 (1985)

Chinese Hamster V79 Cell -

Conc.: 9.75, 19.5, 39, 78.0 and 

156 μg/plate, + - S-9./ 

Unacceptable/ Guideline

Negative. MTI-500 does not appear to be a mutagen in a 

Chinese hamster V79 test system both in the presence or 

absence of rat liver S-9 metabolic activation. Classification: 

unacceptable due to high spontaneous backgrounds.

870.5375 

(84-2)

Clastogenic action 

on bone marrow 

erythrocytes in 

mouse 

micronucleus test.

40449717 (1985)

Acceptable/Guideline

Conc.: 80, 400, and 2000, 

mg/kg.

Negative. MTI-500 does not appear to be clastogenic by the 

mouse micronucleus test system.

870.5375 

(84-2) In vitro clastogenic 

activity in cultured 

human peripheral 

lymphocytes.

40449718 

(1985)/Acceptable/Conc.: 6.25, 

12.5, 25, 50 (main study), 4, 20, 

100, 500, 2500 μg/ml 

(preliminary study) + - S-9.

Negative. MTI-500 is not clastogenic in cultured peripheral

lymphocytes at concentrations of up to 50 ug/ml with and 

without metabolic activation. A significant decrease in 

mitotic index was observed at the highest concentration.

870.5375 

(84-2) In vitro clastogenic 

activity in cultured 

human peripheral 

lymphocytes.

40449719 

(1985)/Acceptable/Conc.: 2.5, 

5.0, 10.0, and 20 μg/ml without 

S-9 and 37.5, 75, 150, and 300 

μg/ml with S-9.

Negative. MTI-500aCO is not clastogenic in cultured 

peripheral lymphocytes at concentrations of up to 20 ug/ml

and 300 ug/ml, with and without metabolic activation, 

respectively. The top concentration reduced the mitotic 

index.

870.5375 

(84-2b)

Assessment of 

lethal DNA 

damage in strains 

of E. Coli.

40449720 

(1985)/Acceptable/Conc.: 320, 

1000, 3200, 10,000 μg/ml with 

and without S-9.

Negative. MTI-500aCO appeared to cause no primary DNA 

damage in 2 E. coli strains deficient in various repair systems.

870.5375 

(84-4) Unscheduled DNA 

synthesis in human 

cell line.

40449721 (1985)

Acceptable/Guideline

Conc.: 9.75, 19.5, 39, 78 and 

156 μg/ml without S-9, and 

2.44, 4.88, 9.75, 19.5, and 39 

μg/ml with S-9.

Negative. MTI-500 did not induce unscheduled DNA 

synthesis at the concentrations tested and appears not to be 

mutagenic in this test system.

870.6200a 

(82-7)

Acute 

neurotoxicity in 

rats.

45932301 (2002)

Acceptable/ Guideline

0, 25, 125, 500, or 2000 mg/kg

NOAEL = 2000 mg/kg,

LOAEL not identified
Etofenprox Human Health Risk Assessment DP No. D405380

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. Study Type MRID No. (Date)/Classification/ Doses Results

870.6200b 

(82-7)

Subchronic 

neurotoxicity study 

in rats.

45925701 (2003)

Acceptable/ Guideline

0, 2500, 5000, 10,000 ppm

M: 0, 149, 299, 604

mg/kg /day

F: 0, 174, 350, or 690 

mg/kg/day)

NOAEL was not identified.

LOAEL = M = 149 mg/kg/day, based on increased liver 

weights in males, abnormal tiptoe gait in females and increase 

rearing behavior in males.

870.6300

(83-6)

Developmental 

neurotoxicity study 

in rats.

46062301 (2003)

Acceptable/Non-guideline

0, 250, 700, 2100 ppm

(0, 21, 57, 169 mg/kg/day)

Maternal NOAEL = 57 mg/kg/day.

Maternal LOAEL = 169 mg/kg/day; based on increased 

rearing counts in females in the FOB.

Offspring NOAEL = 57 mg/kg/day.

Offspring LOAEL = 169 mg/kg/day, based on eye 

abnormalities in both sexes. (Note however that observations 

of eye injury may be the result of altered maternal care of the 

pups and further note that pup behavior was altered for 

auditory startle in both sexes at the high dose.)

From Executive Summary: Analytical data for homogeneity 

and stability analysis were not provided. This study is also 

considered non-guideline at this time due to deficiency in the

memory assessment in the offspring, lack of descriptions for 

behavioral equipment used, and pending a comprehensive 

review of all available positive control data.

870.7485

(85-1)

Metabolism and 

pharmacokinetics 

studies in rats.

40449723 (1985)

Acceptable/Guideline

Single oral dose of 30 or 180 

mg/kg

Majority of etofenprox was absorbed through the GI tract and 

mean peak plasma concentration occurred after 5 hours of oral 

administration. 86-90% was excreted via feces, 6-11% via 

urine and 3.5-4% retained in the body after 5 days of oral 

administration. The compound distributed in the stomach, 

small and large intestines, bile duct, fat and liver. Etofenprox 

accumulates as the parent compound in milk, fat and in tissues 

or organs which contain high fat compositions. About 95% of 

the compound found in fat tissues and milk was in the form of 

unchanged non-metabolized etofenprox. The two major 

metabolic routes included: replacement of the ethyl group 

with a hydrogen (desethyletofenprox), and hydroxylation of 

etofenprox.

870.7485

(85-1)

Metabolism and 

pharmacokinetics 

studies in dogs.

40449722 (1985)

Acceptable/Guideline

single oral dose of 30 mg/kg

Because the chief metabolic products detected were similar 

for the rat and dog, the same route of metabolism was 

proposed for both species. Approximately 90 and 6% of a 

single oral dose was recovered I within 5 days n the feces and 

urine, respectively. Approximately 55% of the fecal 

radioactivity was recovered as unchanged etofenprox. A 

small portion (5%) of fecal radioactivity represented 

metabolites and none represented detected/characterized 

conjugates. Glucuronide and sulfate conjugates were found in 

the bile. It was suggested that unchanged etofenprox found in 

the feces represented mainly compound that had not been 

absorbed from the gut, and metabolites that which had been 

excreted via the bile. Plasma t1⁄2 averaged 13.7 hours but 

there was considerable individual variability in this and other 

pharmacokinetic observations.-
Etofenprox Human Health Risk Assessment DP No. D405380

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. Study Type MRID No. (Date)/Classification/ Doses Results

870.7485

(85-1)

Metabolism and 

pharmacokinetics 

studies in rats.

47132839 (2001)

single oral gavage dose at 33.5 

mg/kg

Acceptable/Non-guideline

This study alone does not satisfy 

the guideline requirement for a 

metabolism study [OPPTS 

870.7485, OECD 417] in rats for 

the following reasons: The 

radiopurity of the test substance 

was low; insufficient 

radioactivity was recovered and 

analyzed for metabolites; and 

reasonable efforts to identify an 

unknown present at 10% of the 

administered dose was not 

performed. However, this study 

along with the metabolism 

studies MRIDs 47132840, 

40449723 and 40449722 satisfy 

the OPPTS 870.7485, OECD 

417 guideline requirements.

Based on the amount of radioactivity that was excreted in the 

urine, at least 14% of the dose was absorbed. The intestinal 

tract and contents (including stomach contents) accounted for 

10.6% of the administered dose, suggesting that absorption 

may not be complete within 48 hours postdose. In the tissues, 

fat had the highest concentration of radioactivity (16.7 μg 

eq/g) accounting for 0.9% of the administered dose. Liver 

and skin also had relatively high concentrations (3.4 and 3.0 

μg eq/g, respectively). The concentration of radioactivity 

isolated in other tissues amounted to <=0.1% of the 

administered dose. Total recovery was 84% within 48 hours 

post dose. Of the administered dose, 67% was found in the 

excreta, and the remaining 17% was found in the tissues and 

carcass. The primary route of excretion was the feces (50% 

of the dose), while urinary excretion accounted for 14% of the 

dose. Major amounts of the radioactive dose were excreted 

during the 0-24 h interval (26% of the dose) and the 24-48 h 

interval (39% of the dose). The cage wash accounted for 2% 

of the dose.

A total of 66.2% of the dose was classified as unknowns or 

identified. An unknown representing 9.63% of the dose was 

found in the urine. In the urine, no other compound was 

found at concentrations >2.27% dose. In the feces, the 

following compounds were isolated and identified at >5% 

dose: (i) 2-(4-ethoxyphenyl)-2-methylpropyl 3-(4-

hydroxyphenoxy)benzyl ether (11.60% dose); (ii) 3-

phenoxybenzyl 2-(4-hydroxyphenyl)-2-methylpropyl ether 

(11.29% dose); (iii) 3-hydroxybenzyl 2-(4-ethoxyphenyl)-2-

methylpropyl ether (5.36% dose); and (iv) parent (11.56% 

dose). No other compound was isolated at >=5% dose. Only 

parent was isolated in the fat.

870.7485

(85-1)

Metabolism and 

pharmacokinetics 

studies in rats.

47132840 (2001)

single oral gavage dose at 30.0 

mg/kg

Acceptable/Guideline

Based on the amount of radioactivity that was excreted in the 

urine, at least 74% of the dose was absorbed. The intestinal 

tract with contents (including stomach contents) and the 

residual carcass accounted for 0.45% and 0.43%, respectively, 

of the administered dose. Each other tissue accounted for 

<=0.06% of the administered dose. Excluding the intestinal 

tract, only the kidney (0.480 μg eq/g) and liver (0.339 μg 

eq/g) had higher concentrations than plasma (0.297 μg eq/g). 

Total recovery was 101% within 48 hours post dose. Of the 

administered dose, 100% was found in the excreta, and the 

remaining 1% was found in the tissues and carcass. The 

primary route of excretion was the urine (74% of the dose), 

while fecal excretion accounted for 15% of the dose. Most of 

the radioactive dose was excreted during the 0-24 h interval 

(81% of the dose). The cage wash accounted for 11% of the 

dose. A total of 87% of the dose was classified as unknowns 

or identified. Two unknowns, one representing 16.49% of the 

dose and another representing 43.57% of the dose, were 

isolated in the urine. 3-Phenoxybenzyl acid was found in the 

urine and accounted for 8.77% of the dose. In the urine, no 

other compound was found at concentrations >2.76% dose. 

In the feces, parent accounted for 3.86% of the dose, and no 

other compound was found at concentrations greater than 

2.45% of the dose. Two unidentified metabolites were found 

in the liver, each representing <0.05% dose.
Etofenprox Human Health Risk Assessment DP No. D405380

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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. Study Type MRID No. (Date)/Classification/ Doses Results

870.7600

(85-3)

Dermal absorption 

study in rats.

44917601 (2001)

Acceptable/ Guideline Dermal absorption = 7 %.

870.7800

4-Week Dietary 

Immunotoxicity 

Study in rats

48280206 (2010)

Acceptable/guideline

0, 560, 2800, 14000 ppm

0, 44, 213, 1053 mg/kg /day

NOAEL = 1053 mg/kg/day

LOAEL > 1053 mg/kg/day (not established for T-cell 

dependent antibody response)

Study conducted in males only

870.7800 4-Week Dietary 

Immunotoxicity 

Study in mice

48280207 (2010)

Acceptable/guideline

0, 320, 1600, 8000 ppm

0, 50, 239, 1116 mg/kg/day

NOAEL = M: 1116 / F: 1528 mg/kg/day

LOAEL > M: 1116 / F: 1528 mg/kg/day mg/kg/day (not 

established for T-cell dependent antibody response)
Etofenprox Human Health Risk Assessment DP No. D405380

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Appendix B. Physical/Chemical Properties and Etofenprox Metabolites

Table B.1. Physicochemical Properties of the Technical Grade Test Compound: Etofenprox.

Parameter Value Reference

Melting point/range 36.4-38.0 oC Docket No. EPA-HQOPP-2007-0804

pH Not available

Density solid (23 oC): 1.157 g/mL

liquid (40.1oC): 1.067 g/mL

Docket No. EPA-HQOPP-2007-0804

Water solubility 22.5 μg/L

5.2 μg/L in pH 4 buffer

12.0 μg/L in pH 9 buffer

MRID 46779713

Solvent solubility at 25 oC 877 g/L in acetone

837 g/L in ethyl acetate

49 g/L in methanol

856 g/L in xylene

MRID 46779713

Vapor pressure 2.5 x 10-8 mm Hg at 25 oC Docket No. EPA-HQOPP-2007-0804

Dissociation constant, pKa Not available

Octanol/water partition coefficient, 

log (POW)

6.9 MRID 46779713

UV/visible absorption spectrum Not available

Table B.2. Chemical Names and Structures of Etofenprox and Metabolites.

Common name/code

Figure C.3.1 ID No.

Chemical name Chemical structure

Etofenprox; MTI-500 1-{[2-(4-ethoxyphenyl)-2-

methylpropoxy]methyl}-3-

phenoxybenzene

α-CO 2-(4-ethoxyphenyl)-2-methylpropyl3-phenoxybenzoate

4′-AcO 2-(4-acetoxyphenyl)-2-

methylpropyl-3-phenoxybenzyl ether

4′-OH 2-(4-ethoxyphenyl)-2-methylpropyl3-(4-hydroxyphenoxy)benzyl ether

DE 3-phenoxybenzyl-2-(4-

hydroxyphenyl)-2-methylpropyl 

ether

DP 3-hydroxybenzyl-2-(4-

ethoxyphenyl)-2-methylpropyl ether
Etofenprox Human Health Risk Assessment DP No. D405380

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Table B.2. Chemical Names and Structures of Etofenprox and Metabolites.

Common name/code

Figure C.3.1 ID No.

Chemical name Chemical structure

m-PBAcid or m-PB-acid 3-phenoxybenzoic acid

m-PB-alc 3-phenoxybenzyl alcohol

O

HO CH2

PENA 2-(4-ethoxyphenyl)-2-methylpropyl 

alcohol

EPMP 2-(4-ethoxyphenyl)-2-methylpropionic 

acid

C

CH3

CH3

C OH 2H5O

O

4′-OH-PBAcid 3-(4-hydroxyphenoxy)benzoic acid

OH-PAlc 2-(4-hydroxyphenyl)-2-methylpropyl 

alcohol
Etofenprox Human Health Risk Assessment DP No. D405380

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Appendix C. Review of Human Research

The PHED Task Force, 1995. The Pesticide Handlers Exposure Database, Version 1.1. 

Electronic Database. Task Force Members: Health Canada, U.S. EPA, and the National 

Agricultural Chemicals Associations, released February 1995. 

The Agricultural Handler Exposure Task Force (AHETF), 2011. The Occupational Handler Unit 

Exposure Surrogate Reference Table. U.S. EPA. Released June 21, 2011. 

Data from the Outdoor Residential Exposure Task Force (ORETF). 

HED Residential Standard Operating Procedures (2012). 
Etofenprox Human Health Risk Assessment DP No. D405380

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Appendix D. Residential Exposure/Risk Summary Tables

Table E.1. Residential Handler Inhalation Exposure and Risk Estimates.

Exposure Scenario

App.

Rate

Amount 

Handled / 

Area 

Treated

Inhalation

Unit 

Exposures

(mg/lb ai)

Inhalation 

Dose 

(mg/kg/day)

Inhalation 

MOE Worker 

Activity

Formul

-ation

App.

Equipment

App. 

Type

M/L/A Liquid

Manually 

pressurized 

handwand

Spot, 

Crack &

Crevice

0.048

lb 

ai/gal

0.5 gal 1.1 0.000330 32,000

Applicator Liquid Aerosol Can

Spot, 

Bed 

Bug

0.01

lb 

ai/can

0.5 cans 3 0.000188 57,000

Applicator Liquid Aerosol Can Broadcast

0.01 

lb 

ai/can

1 can 3 0.000375 28,000

Applicator Liquid Aerosol Can Space 

Spray

0.01 

lb 

ai/can

0.025 cans 3 0.0000938 110,000

Applicator Fogger Fogger

Outdoor 

Patio 

Fogger

0.005

5 lb 

ai/day

1 can 3 0.000205 52,000

Table E.2. Inhalation Post-Application Exposure & Risk Estimates from Mosquito Adulticide Use.

Population

Air 

Concentration 

Estimate

(mg/m3)

Breathing Rate 

(m3/hr)

Exposure 

Duration 

(hours)

Dosed

(mg/kg/day) MOEe

Aerial ULV (100 ft release height)

Adults 0.0029

a 0.64 0.33 0.00000766 1,400,000

Children 1 to <2 

years old

0.0030

b 0.33 0.33 0.0000297 360,000

ULV Truck Fogger

Adults 0.0077c0.64 0.33 0.0000203 520,000

Children 1 to <2 

years old 0.0077c

0.33 0.33 0.0000762 140,000

a Air concentration estimate produced from AGDISP Model at approximate 6 feet from ground.

b Air concentration estimate produced from AGDISP Model at approximate 3 feet from ground.

c Air concentration = Application Rate (0.007 lb ai/A) x 1 A/43,560 ft2x 10.7 ft2/m3x 454,000 mg/lb x dilution factor (0.01) = 

0.77 mg/m3

d Dose (mg/kg/day) = Air concentration (mg/m3) x Breathing Rate (m3/hr) x Exposure Time (hr) / Body Weight (80 kg adult, 

11 kg child 1 to <2 years old)

e MOE = NOAEL (10.6 mg/kg/day / Dose (mg/kg/day)

Table E.3. Short-Term Incidental Oral Post-application Risk Estimates to Children 1 to<2 Year Old from 

Mosquito Adulticide Use.

Scenario Maximum Depositiona

(μg ai/cm2)

Total Turf 

Residueb

(μg/cm2)

Soil 

Residuec

(μg/g)

Average Daily Dosed

(mg/kg/day) MOEe

Hand-to-Mouth 0.026 0.00026 - 3.52E-5 5.7E+5

Object-to-Mouth 0.026 0.00026 - 1.07E-6 1.9E+7

Incidental Soil Ingestion 0.026 - 0.0174 7.8E-8 2.6E+8
Etofenprox Human Health Risk Assessment DP No. D405380

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a Maximum deposition by Air ULV or Ground ULV = application rate (0.007 lb ai/A) x maximum deposition rate (33%) / (43,560 ft2/A) x 

(4.54E+8 μg/lb) x (1.08E-3 ft2/cm2) = 0.026 μg/cm2. 

b Turf transferrable residue (TTR) (μg/cm2) = fraction of ai retained on foliage (1%) x maximum deposition (0.026 μg ai/cm2) = 0.00026 μg/cm2.

c Soil residue (Srt) (μg/g) = Deposition (0.026 μg ai/cm2) x 1/cm x 0.67cm3/g soil = 0.0174 μg/g.

d Average daily dose (mg/kg/day) = 

Hand-to-Mouth Dose = hand residue loading (mg/cm2) × fraction of hand mouthed (0.127) × 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 (0.48))^(Number of hand-to-mouth events per hour (13.9 

events/hr) ÷ # of replenishment intervals/hr (4 int/hr))) ÷ body weight (11 kg).

Object-to-Mouth Dose = 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 (0.48))^(# Object-to-Mouth 

Events/hr (8.8 events/hr) ÷ # replenishment intervals/hr (4))) ÷ body weight (11 kg).

Soil Ingestion = soil residue (μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 g/μg) ÷ body weight (11 kg).

e MOE = NOAEL/ADD, where Short-term incidental oral NOAEL = 20mg/kg/day, with an LOC of 100.

Table E.4. Aerosol Can Inhalation Exposure Study (MRID 46188618) Measures for PY and PBO Normalized to 

Application Rate of Etofenprox Aerosol Can

Active

Ingredient

Study Application 

Rate A

(lb ai/1000 ft3)

a

Average Breathing 

Zone Concentration 

Post-Applicationb

(mg/m3)

Etofenprox 

Application 

Ratec

(lb ai/1000 ft3)

Adjusted 

Breathing Zone 

Concentrationd

(mg/ m3)

b

Average Adjusted 

Etofenprox 

Breathing Zone 

Concentration 

(mg/m3)

Immediately (0 -5 Minutes) Post-application

PY 0.000050 0.067

0.00014

0.19

0.26

PBO 0.00010 0.24 0.34

a. Based upon the application of 9.31 grams of a product containing 0.5% pyrethrins and 1% PBO by weight to room with an 

internal volume of 2048 cubic ft.

b. Air concentrations measured in MRID 46188618.

c. Etofenprox rate based on a 10 second spray of a 0.5% ai 12-oz aerosol can to 1000 ft3.

d. Adjusted Breathing Zone Concentration (mg/m3) = Average Breathing Zone Concentrations (mg/m3) x (Etofenprox App. 

Rate (0.00014 lb ai/1000 ft3) / PY-PBO Study App. Rate (lb ai/1000 ft3))

e.

Table E.5. Etofenprox Estimated Post-application Inhalation Short- and Intermediate-Term Risk to Adults and 

Children 1 to <2 Years Old Immediately After an Indoor Space Spray Application Using PY/PBO Study Data

Exposed 

Individual

Average Etofenprox 

Breathing Zone 

Concentration 

(mg/m3)

Inhalation 

Rate 

(m3/hr)

Indoor Air 

Exchange 

Rate (1/hr)

Exposure 

Time (hr)

Exposurea

(mg/day)

Inhalation 

Doseb

(mg/kg/day)

MOEc

Immediately (0 -5 Minutes) Post-application

Adult

0.26

0.64

0.45

16 0.37 0.0046 2,300

Children 0.33 18 0.19 0.017 630

f. a. Inhalation Exposure (mg/day) = (Average Etofenprox Breathing Zone Concentration (mg/m3) x Inhalation Rate 

(m3/hr) / Indoor Air Exchange Rate (1/hr)) x (1 – e ^ (- Indoor Air Exchange Rate (1/hr) * Exposure Time (hr))

g. b. Inhalation Dose (mg/kg/day) =Inhalation Exposure (mg/day) / Body Weight (Adult, 80 kg; Child, 11.4 kg)

h. c. MOE = Inhalation NOAEL (10.6 mg/kg/day) / Inhalation Dose (mg/kg/day)); Level of concern is an MOE = 100.

Table E.6. Residential Post-application Non-cancer Exposure and Risk Estimates for Existing Uses of 

Etofenprox.

Lifestage Exposure Scenario Route of Exposure Dose 

(mg/kg/day) MOE

Adult

Liquid Crack & Crevice Surface Directed 

Spray

Inhalation 0.0000648 160,000

1 to 2 yr olds

Inhalation 0.000273 39,000

Oral Hand to Mouth (Carpet) 0.000177 11,000

Oral Hand to Mouth (Hard Surface) 0.000589 34,000
Etofenprox Human Health Risk Assessment DP No. D405380

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Table E.6. Residential Post-application Non-cancer Exposure and Risk Estimates for Existing Uses of 

Etofenprox.

Lifestage Exposure Scenario Route of Exposure Dose 

(mg/kg/day) MOE

Oral Object to Mouth (Carpet) 0.000235 85,000

Oral Object to Mouth (Hard Surface) 0.000157 130,000

Adult

Aerosol Spray Can (12 oz, 0.5%, 0.01 lb 

ai/can) for Flying insects

Inhalation 0.00462 2,300

1 to 2 yr olds

Inhalation 0.0170

a

630

Oral Hand to Mouth (Carpet) 0.0036 5,600

Oral Hand to Mouth (Hard Surface) 0.0012 17,000

Oral Object to Mouth (Carpet) 0.000478 42,000

Oral Object to Mouth (Hard Surface) 0.000319 63,000

1 to 2 yr olds

Aerosol Spray Can (17.5 oz, 1%, 0.01 lb 

ai/can) for Crawling Insects

Perimeter/Spot (Pin Stream)

Oral Hand to Mouth (Carpet) 0.00642 3,100

Oral Hand to Mouth (Hard Surface) 0.00216 9,300

Oral Object to Mouth (Carpet) 0.000863 23,000

Oral Object to Mouth (Hard Surface) 0.000575 35,000

Adult

Aerosol Spray Can (17.5 oz, 1%, 0.01 lb 

ai/can) for Crawling Insects

Perimeter/Spot (Coarse)

Inhalation 0.0000043 2,500,000

1 to 2 yr olds

Inhalation 0.000018 580,000

Oral Hand to Mouth (Carpet) 0.0265a750

Oral Hand to Mouth (Hard Surface) 0.0088 2,300

Oral Object to Mouth (Carpet) 0.00119 17,000

Oral Object to Mouth (Hard Surface) 0.00079 25,000

1 to 2 yr olds Cat from Spot-on

ST/IT Oral (small cat) 0.00359 5,600

LT Oral (small cat) 0.00359 1000

ST/IT Oral (medium cat) 0.00431 4,600

LT Oral (medium cat) 0.00431 860

1 to 2 yr olds Dog from Spot-on

ST/IT Oral (small dog) 0.00910a2,200

LT Oral (small dog) 0.00910 410

ST/IT Oral (medium dog) 0.00780 2,600

LT Oral (medium dog) 0.00780 470

ST/IT Oral (large dog) 0.00828 2,400

LT Oral (large dog) 0.00828 450

1 to 2 yr olds Indoor Pressurized Fogger (6 oz, 1% ai, 

2.4 μg ai/cm2)

Oral Hand to Mouth (Carpet) 0.0141 1,400

Oral Hand to Mouth (Hard Surface) 0.00471 4,200

Oral Object to Mouth (Carpet) 0.00188 11,000

Oral Object to Mouth (Hard Surface) 0.00125 16,000

Adult

Outdoor Fogger (17.5 oz, 0.5% ai, 0.0238 

lb ai/A)

Inhalation 0.00368 2,900

1 to 2 yr olds

Inhalation 0.0138 770

Oral Hand to Mouth 0.000363 29,000

Oral Object to Mouth 0.00011 960,000

Soil Ingestion 0.000000131 13,000,000

a

Incidental oral exposures combined, since they can co-occur on the same day from treatment to control fleas.