### Etofenprox Human Health Risk Assessment DP No. D405380



### UN I TED STATES ENVIRONMENTAL PRO T ECTION AG E NCY

WASHIN GT ON, D.C. 20 460

MEMORANDUM

Date: September 

### 12, 2013 O FFI CE OF CHEMICAL SAF ETY AND POLL U TION 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 E

7925 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 40 CFR: § 180.620 MRIDNo.: NA



### 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 t oxicology 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 Hea l th 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

................... .. ................. .. ... .. ................. 1 4 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

....... .. .. .. ...... .. . .. ... .. .. .. ...... .. .......... 1 5 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

Page 2 of 46

### 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

Page 4 of 46 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 moie ty 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 a n 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 perso ns under direct supervision of those authorized by the state, tribal, or local pesticide regulatory agencies. The proposed/amended label s 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 offsp ring 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, theref ore, 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 t here are potential short

- term p ost

application exposures to adults and children. Additionally, all of the existing residential uses have been reassessed to reflect updates to the HED 2012 Residential SOPs 1 

### . 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

Page 5 of 46 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 toler ance

- level residues for livestock commodities . The assessment also incorporated estimated percent crop treated (%CT) values, and used default processing factors. Estimated drinking water concentrati ons (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)] f or 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 3 2 % 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 int ermediate

- 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 resident ial 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, f urther refinement using etofenprox

- specific field trial data to estimate potential residues re sulting 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 h andling activities (e.g. mixing, loading, application). Dermal toxicity was not identified, so a dermal exposure assessment wa s 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

Page 6 of 46 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 t hese 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 tolerance s 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 Sectio n 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 S ection F to propose tolerances for livestock commodities.

The following deficiencies would r efine 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 app lications 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 Tol erance Considerations

2.2.1 Enforcement Analytical Method

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 7 of 46 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

ver ification 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: T he proposed GC/MS enforcement method (RCC Study NO. 791245) in combination with the GC/MS confirmato ry 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 tolera nces 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 p ermanent tolerances be established for livesto ck 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

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 8 of 46 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, t he 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 applicat ions 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 app lications (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 dat a 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 Developmen tal ( 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

Page 9 of 46 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 In troduction

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 EC s , SCs, granular s , pressurized liqu id (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 formul ation: Z enivex 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, request ed 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 tolerance s for residues of the insecticide etofenprox 2

- (4

- ethyoxyphenyl)

- 2

- methylpropyl 3

- phenoxybenzyl e ther 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 SOPs 2



### .

3.1 Chemical Identity

Table 3.1

. Test Compound Nomenclature. Compound

Common name Etofenprox Company experimental name MTI

- 500
IUPAC name 2

- (4

- E thoxyphenyl)

- 2

- methylpropyl 3

- phenoxybenzyl ether
CAS name 1

- [[2

- (4

- E thoxyphenyl)

- 2

- methylpropoxy]methyl]

- 3

- phenoxybenzene CAS registry number 80844

- 07

- 1
End

- use product s (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

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 10 of 46 Table 3.1

. Test Compound Nomenclature.
Chemical structure of α

- CO metabolite

IUPAC name 2

- (4

- E thoxyphenyl)

- 2

- methylpropyl

- 3

- phenoxybenzoate



### 3.2 Physical/Chemical Characteristics

Etofenprox has a log octanol/water partition coefficient (log K ow 

### ) 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 pastu re land. The two end

- use products a re 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; b y 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 labe ls 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.

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 11 of 46 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

M osquito 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 application s 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 ma y 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 afore mentioned 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 Population s," ( 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

- establi shed 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 pestic ide 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 asse ssments 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 trea ted areas following application are evaluated. Further considerations

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 12 of 46 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 su bmitted (V. Chen, D 385299

, 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 p yrethroids 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 m embrane 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 st ructure. 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 d oes 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 e tofenprox 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 w ere 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 incl uded centrilobular hepatocyte enlargement.

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 13 of 46 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 mate rnal 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 ob served 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/locomo tor 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 d oses 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 no t 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 i n 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 de velopment 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 qu antification 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 a n acute eye nor dermal irritant (Toxicity Categories IV), or an acute dermal sensitizer. However, s kin irritation was observed after repeated exposure to etofenprox in rabbits. The acute toxicity of etofenprox technical ( TGAI ) , as well as the overall acu te 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 conc entrations 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 deter mined to be 7.0%.

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 14 of 46 4. 2 Safety F actor 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 da ta 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, n or in the 2

- generation rat reproduction study. Although infa nts 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 ( S ection 4 .3). Therefore, the human health risk

assess ment is protective of thyroid toxicity and neurotoxicity.

4.2.1 Completeness o f 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 N eurotoxicity

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 o f 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 respons e 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 subchron ic 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 F 0 

### generation and decreased (n on

- statistically significant) mobility (both sexes) and rearing behavior (males) in the F 1 

### generation. In the 2

- generation reproduction study F 1 

### 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 NOAEL s ; (3) the signs of neurotoxicity are well

- characterized in terms of

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 15 of 46 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 observ ed. 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
exposur e is low.

4.2.3 Evidence o f Sensitivity/Su sceptibility in the Developing o r 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 one

generation/developmental study. In the two

- generation reproduction toxicity study, toxicity in the offspring occurred at the level of parental to xicity (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 pos sible altered, treatment

- related maternal behavior.

4.2.4 Residual Uncertainty in the Exposure Datab ase

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 model s 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 R esidential 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.

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 16 of 46 4. 3 Toxicity Endpoint and Point of D eparture 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 wit h 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 long

term incidental oral exposures to children from treated pets was a NOAEL of 3.7 mg/kg/day from the comb ined 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 Non

Occupational 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

UF A = 10x

UF H = 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 Intermediate

Term (1

- 30 days and 1

- 6 months ) NOAEL =

20 mg/kg/day FQPA = 1x

UF A = 10x

UF H = 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

UF A = 10x

UF H = 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.

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 17 of 46 Table 4

. 3 .1

. Summary of Toxicological Doses and Endpoints for Etofenprox for Use in Dietary and Non

Occupational 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

UF A = 10x

UF H = 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 ob served adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = 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

UF A = 10x

UF H = 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 ob served adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = 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 asse ssments, 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

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 18 of 46 endpoint for dermal exposure risk assess ment 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 resid ue 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 H ED Residues of Concern Knowledgebase Subcommittee (HED ROCKS Report, D352227, 05/20/ 20 08) 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 Crop s None None

Livestock Ruminant s 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 cont rol ha ve been accepted by HED after review of the residue data and discussion by HED’s ChemSAC (ChemSAC minutes, 0 9/29/2010 and 03/13/2013 ). Each trial consisted of three treated plots (one for each commodity).

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 19 of 46 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 fo llowing multiple application s using conservative ap plication 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 application s (C. Peck, D407817, 02/28/2013) . Based on the data generated by IR

- 4 and EFED

s upporting 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 applicat ions (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
eto fenprox 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. Residu es are not expected to exceed 4.0 on fat and meat byproducts, and 0.20 ppm i n meat of hogs. Tolerances sho uld be proposed as listed i n 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

, D 398044

, 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.”

EDWC s in surface water and in gro und 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 wate r concentrations from a drinking water assessment conducted in 2010 (G. Orrick,

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 20 of 46 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 Foggers A,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 - 3 3.0 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 Wate r 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 prop osed crops used in the dietary assessment.

5.4.2 Percent Crop Treated Used in Diet ary 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 d uring 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 u ses 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 gi ven 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

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 21 of 46 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 co uld 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 e tofenprox 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 la nd 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) ex posure 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 S urvey, 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 res ults 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 underesti mate exposure. For future uses of etofenprox, f urther 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.

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 22 of 46 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) 0.00 4154 11
Children 1

- 2 years old* 0.011805 32
Children 3

- 5 years old 0. 009 360 25
Children 6

- 12 years old 0. 0046 93 13
Youth 13

- 19 years old 0. 0027 32 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. 002 327 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 SOPs 3 

### along 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 cr op, pasture, and range land . However, t here are potential post

- application exposures to adults and children from the ULV aerial and ground

based fogger applications in the vicinity of residential areas.

3 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 23 of 46 Table 6.0 . Proposed and Existing Use Patterns an d 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 Surface

directed 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/cm 2 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 SOPs 4



### . 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 o ral 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 LO C 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 be en 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).

4 Available: http://www.epa.gov /scipoly/SAP/meetings/2009/120109meeting.html

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 24 of 46 Short

- term residential handler inhalation MO Es were not of concern to HED, and range d 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 previo usly 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 dog s were also assessed.

Chemical

- specific exposure data for use of etofenprox as a mosquito adulticide have not been submitted; therefore, the 2012 Residential SOPs 5 

### and the AGDRIFT model were used to estimate exposures following etofenprox use as a mosqu ito 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 p osition 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. Ekb iad 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.

AGD ISP 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 tre atment 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 residi ng 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.

5 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 25 of 46 For children 1 to <2 years old, short

- term post

- application inhalation MOEs range fr om 6 3 0 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 260,000,00 0

.
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 , l ong

- 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) be cause 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 differe nt products containing etofenprox on the same day would be low.

I t 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 surf aces 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 tr eat 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 conta ct 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 we re then combined with post

- application inhalation exposure resulting from i nhalation 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, t he most conservative combined post

- applicatio n 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 = 0.017 0 mg/kg/da y). 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 t he air and the

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 26 of 46 carpet may contain residues following an aerosol spray indoors, so HED combined hand

- to

mouth e xposure from treated indoor surfaces with inhalation exposure following indoor aerosol
sprays . The combination of exposure from resulted in a combined MOE of 5 70 , 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
Child ren (1

-

<2 years) Exposure through air Inhalation 0.017 0 630 570

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

560 Hand

- to

- Mouth 0.0265 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 cal culated 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 aeria l 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 etofenpro x 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

MOE 1 Incidental Oral

Hand

- to

- Mouth Dose (mg/kg/day) Incidental

Oral MOE 1 Total

Combined MOE 2
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/MOE inhal ) + (1/MOE incid 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 f rom all residential uses of etofenprox are provided in

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 27 of 46 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 Residen tial Exposures for the Etofenprox Aggregate Assessment. 1

Lifestage Residential Handler Residential Post

- application Dose (mg/kg/day) 2 MOE 3 Dose (mg/kg/day) 4 MOE 5

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 y ears (Treatment for flying insects) N/A 0.017 0 0.0036 0.020 6 630 5,600 570
Long

- Term Children 1 to<2 y ears ( 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 do ses identified in D1

. 4 Residential Post

- application Dose = the highest post

- application dose for each applicable lifestage of all scenar ios 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 o 

### C ), and the low proposed use rate (0. 007 lb ai/A). However, volatilization of pesticides may be a source of post

- applica tion inhalation exposure to individuals nearby pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 6 

### . 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 Drif t 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

6 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 28 of 46 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 hydraul ic 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 Characterizati on

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, potentia l 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 mosquit o 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 ref erence 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 residen tial (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 o f the residential exposure scenarios considered in the aggregate assessment, see Section 6.4.

The aggregate MOE for adult s, 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 da ta 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

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 29 of 46 LOC for Aggregate Risk 1 Dietary

MOE 2 MOE Oral

Residential Exposure 3 MOE

Inhalation Residential Exposure 4 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 i ntermediate

- 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 (0.0 036 mg/kg/day )]. Residential exposure values can be found in Table 6.4.
4 Adult inhalation MO E = [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 MO E = [short

- term inhalation NOAEL (10.6 mg/kg/day )/ high end inhalation residential inhalation exposure (0.017 0 mg/kg/day) ]. Residential exposure values can be found in Table 6.4.
5 MOE Aggregate = 1/[(1/ MOE dietar y ) + (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 ide ntified for etofenprox , incidental oral exposure is not expected for adults, and inhalation exposure is not expected for adults from treating pets ; therefore a n 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 us ing 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.

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 30 of 46 Table 7. 3 . Long

- Term/Chronic Aggregate Risk Calculations.

Population Long

- Term/Chronic Scenario

LOC for Aggregate Risk 1 Dietary

MOE 2 MOE Oral

Residential Exposure 3 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 y ears 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 r esidential 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 pesticide s 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 t o 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 ‘pyrethroi ds’) 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 chann el 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 ne urological 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 res ulting 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. Eto fenprox 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 an d 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

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 31 of 46 cumulating effects from substances found to have a common mechani sm on EPA’s website at http://www.epa.gov/pesticides/cumulative/

.

9.0 Occupational Exposure/Risk Characterization

HED has evalu ated 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 a pplied 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. Ho w ever, IR

- 4 has pr oposed 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 post

application activities. However, s ince the same endpoint a nd 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 e tofenprox 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 s ummar y of the short

- term inhalation risks for occupational handlers applying etofenprox is
prov ided 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 etofenpr ox mosquito adulti cide applications ranged from 8,600 to 24 0,000

.

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

.

Scenario Application Rate 1 (lb ai/acre) Unit

Exposure 2 (mg/lb ai) Units

Treated 3 (acres/day) Average

Daily Dose 4 (mg/kg/day) Short

- and

Intermediate

term MOE 5
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

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 32 of 46 Table 9.1 . Occupational Handler Inhalation Exposure and Risk Estimates for Etofenprox

.

Scenario Application Rate 1 (lb ai/acre) Unit

Exposure 2 (mg/lb ai) Units

Treated 3 (acres/day) Average

Daily Dose 4 (mg/kg/day) Short

- and

Intermediate

term MOE 5 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 re

entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop p roduction, 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 tre ated areas following application, and therefore, no quantitative assessment is required.

9.2.2 Inhalation Post

- A pplication 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 o 

### C ), and the low proposed use rate (0. 007 lb ai/A). However, there are multiple potential sources of post

appli cation 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 s ought 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 revi sit 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, 03/14/201 3: 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 t he 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 A ppendix 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 tha t 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

Page 35 of 46 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 LD 50 ≥ 5000 mg/kg IV

870.1200 Acute Dermal

- Rabbit 40237710 LD 50 ≥ 2100 mg/kg III

870.1300 Acute Inhalation

- Rat 40237705 LC 50 ≥ 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 o n 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 li ver 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 ery thma, 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

Page 36 of 46 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 me asured 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. Dev elopmental 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 system ic 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

Page 37 of 46 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 concentrati on 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 b ackgrounds.

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 lymphoc ytes. 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.

870.620 0a (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

Page 38 of 46 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: A nalytical 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 S ingle 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% r etained 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 hydroxylat ion 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. A pproximately 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 i n 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 consider able individual variability in this and other

pharmacokinetic observations.

-

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 39 of 46 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 metabo lites; 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 requ irements. 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 ti ssues 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 int erval (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 co ncentrations >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 admini stered 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 a nd 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 accoun ted 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

Page 40 of 46 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

Page 41 of 46 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

- HQ

OPP

- 2007

- 0804 pH Not available Density solid (23 oC): 1.157 g/mL liquid (40.1oC): 1.067 g/mL Docket No. EPA

- HQ

OPP

- 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

- HQ

OPP

- 2007

- 0804 Dissociation constant, pK a Not available Octanol/water partition coefficient, log (P OW ) 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

- methylpropyl

3

- phenoxybenzoate

4 ′

- AcO 2

- (4

- acetoxyphenyl)

- 2

- methylpropyl

- 3

- phenoxybenzyl ether

4 ′

- OH 2

- (4

- ethoxyphenyl)

- 2

- methylpropyl

3

- (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

Page 42 of 46 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

PENA 2

- (4

- ethoxyphenyl)

- 2

- methylpropyl alcohol

EPMP 2

- (4

- ethoxyphenyl)

- 2

- methylpropionic acid

4 ′

- OH

- PBAcid 3

- (4

- hydroxyphenoxy)benzoic acid

OH

- PAlc 2

- (4

- hydroxyphenyl)

- 2

- methylpropyl alcohol

### Etofenprox Human Health Risk Assessment DP No. D405380

Page 43 of 46 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

Page 44 of 46 Appendix D

. Residen tial 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 Broad

cast 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

Co n centration Estimate (mg/m 3 ) Breathing Rate

(m 3 /hr) Exposure

Duration (hours) Dose d

(mg/kg/day) MOE e

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 0.0077 c 0.64 0.33 0.0000203 520,000

Children 1 to <2 years old 0.0077 c 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 ft 2 x 10.7 ft 2 /m 3 x 454,000 mg/lb x dilution factor (0.01) = 0.77 mg/m 3 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 Deposition a (μg ai/cm 2 ) Total Turf

Residue b (μg/cm2 ) Soil

Residue c (μg/g) Average Daily Dose d

(mg/kg/day) MOE e

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

Page 45 of 46 a Maximum d eposition by Air ULV or Ground ULV = application rate (0.007 lb ai/A) x maximum deposition rate (33%) / (43,560 ft 2 /A) x (4.54E+8 μg/lb) x (1.08E

- 3 ft 2 /cm 2 ) = 0.026 μg/cm 2

. b Turf transferrable residue (TTR) (μg/cm 2 ) = fraction of ai retained on foliage (1%) x maximum deposition (0.026 μg ai/cm 2 ) = 0.0 002 6 μg/cm 2

. c Soil res idue ( Srt ) (μg/g) = Deposition (0.026 μg ai/cm 2 ) x 1/cm x 0.67cm 3 /g soil = 0.0174 μg/g. d Average daily dose (mg/kg/day) = Hand

- to

- Mouth Dose = hand residue loading (mg/cm 2 ) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm 2 ) × 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/cm 2 ) × unit conversion factor (0.001 mg/μg) × object surface area mouthed / event (10

cm 2 /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 Shor t

- 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 ft 3 ) a Average Breathing

Zone Concentration
Post

- Application b (mg/m 3 ) Etofenprox

Application Rate c (lb ai/1000 ft 3 ) Adjusted

Breathing Zone Concentration d (mg/ m 3 ) b Average Adjusted

Etofenprox Breathing Zone Concentration (mg/m 3 ) 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 ft 3

. d. Adjusted Breathing Zone Concentration (mg/m 3 ) = Average Breathing Zone Concentrations (mg/m 3 ) x (Etofe n prox 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/m 3 ) Inhalation

Rate (m 3 /hr) Indoor Air

Exchange Rate (1/hr) Exposure

Time (hr) Exposure a

(mg/day) Inhalation

Dose b (mg/kg/day) MOE c

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/m 3 ) x Inhalation Rate (m 3 /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 conce rn 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

Page 46 of 46 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 0.017 0 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) 0.0265 a 750
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 ) 0.00910 a 2,200

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/cm 2 ) 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.