UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: 9/15/2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Prallethrin. Human Health Risk Assessment for the Tolerance Petition to 

Amend the Section 3 Mosquito Adulticide Registration to Include Use of the 

Insecticide Over All Crops 

PC Code: 128722 

Decision No.: 470627 

Petition No.: 2F8090 

Risk Assessment Type: Single Chemical 

Aggregate 

TXRNo.: NA 

MRIDNo.: NA 

FROM: 

Ray Kent, Ph.D., Toxicologist 

Wade Britton, Industrial Hygie 

DP Barcode: 0420116 

Registration Nos.: I 021-1795, 1021-2562 

Regulatory Action: Section 3 Registration 

CaseNo.: 7418 

CAS No.: 23031-36-9 

40 CFR: § 180.545 

HED Risk Assessment Review Comm ttee 

TO: Kevin Sweeney/Richard Gebken, RM Team 10 

ln$ecticide Branch (IB) 

Registration Division (7505P) 
Prallethrin Human Health Risk Assessment DP No. D420116 

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

human health risk assessment for the proposed label amendment for the use of the insecticide 

prallethrin as a mosquito adulticide. 

This document contains the human health risk assessment associated with this action and 

incorporates updated endpoints for risk assessment, updated percent food handling establishment 

treated assumptions, as well as the most recent data and assumptions for conducting residential 

and occupational exposure assessments. No risks of concern were identified for the proposed 

label amendment. 

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Prallethrin Human Health Risk Assessment DP No. D420116

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1.0 Executive Summary............................................................................................................ 5

2.0 HED Recommendations...................................................................................................... 8

2.1 Data Deficiencies/Conditions of Registration ................................................................ 8

2.2 Tolerance Considerations................................................................................................ 9

2.2.1 Enforcement Analytical Method................................................................................. 9

2.2.2 International Harmonization ....................................................................................... 9

2.2.3 Recommended Tolerances.......................................................................................... 9

2.2.4 Revisions to Petitioned-For Tolerances.................................................................... 10

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

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

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

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

3.3 Pesticide Use Pattern..................................................................................................... 11

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

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

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

4.1 Toxicology Studies Available for Analysis.................................................................. 15

4.2 Toxicological Profile .................................................................................................... 15

4.3 Pyrethroid Pharmacokinetic and Pharmacodynamic Profile ........................................ 16

4.3.1 Pharmacokinetics...................................................................................................... 16

4.3.2 Pharmacodynamics................................................................................................... 18

4.3.3 Critical Duration of Exposure................................................................................... 19

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ..................................... 21

4.4.1 Completeness of the Toxicology Database............................................................... 22

4.4.2 Evidence of Neurotoxicity ........................................................................................ 23

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ........... 23

4.4.4 Residual Uncertainty in the Exposure Database....................................................... 24

4.5 Toxicity Endpoint and Point of Departure Selections .................................................. 25

4.5.1 Dose-Response Assessment...................................................................................... 25

4.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment ........... 28

4.5.3 Cancer Classification and Risk Assessment Recommendation................................ 28

4.5.4 Summary of Points of Departure and Toxicity Endpoints ....................................... 28

5.0 Dietary Exposure and Risk Assessment ........................................................................... 31

5.1 Metabolite/Degradate Residue Profile.......................................................................... 31

5.1.1 Summary of Plant and Animal Metabolism Studies................................................. 31

5.1.2 Summary of Environmental Degradation ................................................................. 31

5.1.3 Comparison of Metabolic Pathways......................................................................... 32

5.1.4 Residues of Concern Summary and Rationale.......................................................... 32

5.2 Food Residue Profile..................................................................................................... 32

5.3 Water Residue Profile ................................................................................................... 33

5.4 Dietary Risk Assessment .............................................................................................. 33

5.4.1 Description of Residue Data Used in Dietary Assessment....................................... 34

5.4.2 Percent Crop Treated Used in Dietary Assessment .................................................. 35

5.4.3 Acute Dietary Risk Assessment................................................................................ 35

5.4.4 Chronic Dietary Exposure Assessment..................................................................... 36
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5.4.5 Summary Table......................................................................................................... 36

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ................................... 36

6.1 Residential Handler and Post-Application Exposure and Risk Estimates.................... 37

6.2 Post-Application Exposure ........................................................................................... 39

6.3 Residential Risk Estimates for Use in Aggregate Assessment ..................................... 43

6.4 Residential Bystander Post-Application Inhalation Exposure...................................... 45

6.5 Spray Drift .................................................................................................................... 45

7.0 Aggregate Exposure/Risk Characterization...................................................................... 45

7.1 Acute Aggregate Risk................................................................................................... 45

7.2 Short-Term Aggregate Risk Estimates......................................................................... 46

8.0 Cumulative Exposure/Risk Characterization.................................................................... 47

9.0 Occupational Exposure/Risk Characterization ................................................................. 47

9.1 Occupational Handler Exposure/Risk Estimates.......................................................... 48

9.2 Post-Application Risk ................................................................................................... 50

9.2.1 Dermal Post-Application Risk .................................................................................. 50

9.2.2 Inhalation Post-Application Risk.............................................................................. 50

10.0 References......................................................................................................................... 51

Appendix A. Toxicology Profile.................................................................................................. 52

A.1 Toxicology Data Requirements .................................................................................... 52

A.2 Toxicity Profile Tables ................................................................................................. 53

A.3 Hazard Identification and Endpoint Selection .............................................................. 56

A.4 Human Equivalent Analysis ......................................................................................... 60

A.5 Pyrethroid Cumulative Screen ...................................................................................... 63

Appendix B. Physical/Chemical Properties................................................................................. 67

Appendix C. Review of Human Research ................................................................................... 68

Appendix D. Aggregate Risk Calculations.................................................................................. 69
Prallethrin Human Health Risk Assessment DP No. D420116

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1.0 Executive Summary

Prallethrin (CAS name 2-methyl-4-oxo-3-(2-propyn-1-yl)-2-cyclopenten-1-yl-2,2-dimethyl-3-(2-

methyl-1-propen-1-yl)cyclopropanecarboxylate, CAS number 23031-36-9) is a pyrethroid 

insecticide able to effect the quick knockdown of target pests. Prallethrin is currently registered 

for use as a mosquito adulticide in outdoor residential and recreational areas. The registrant, 

McLaughlin Gormley King Company (MGK), petitioned the Agency for a label amendment that 

allows the end use products to be “applied over agricultural areas for the control of adult 

mosquitoes within or adjacent to these areas.” Prallethrin is also registered for a variety of 

residential uses for control of pests on pets, turf, and in homes and commercial settings, 

including food handling establishments (FHEs). There are no other food uses for prallethrin. A 

tolerance is established at 1.0 ppm in/on all food items to cover the food handling use (40 CFR 

§180.545). The registrant has proposed that this tolerance also cover residues that might result 

from the amended use pattern for the mosquito adulticide.

Prallethrin is classified as a type I pyrethroid. Type I pyrethroids lack an alpha-cyano moiety 

and induce a syndrome consisting of aggressive sparring, altered sensitivity to external stimuli, 

and fine tremor progressing to whole-body tremor and prostration in rats. These Type I 

pyrethroid-specific behaviors are collectively described as the T-syndrome. The adverse 

outcome pathway (AOP) shared by pyrethroids involves the ability to interact with voltage-gated 

sodium channels (VGSCs) in the central and peripheral nervous system, leading to changes in 

neuron firing, and ultimately neurotoxicity. 

The toxicology database for prallethrin is considered complete with respect to guideline toxicity 

studies. However, the Agency lacks additional information to fully characterize the potential for 

juvenile sensitivity to the neurotoxic effects of pyrethroids. The toxicity database for prallethrin 

does include studies that can be used to characterize most effects, including potential 

developmental, reproductive, and neurotoxic effects. The prallethrin database lacks acceptable 

immunotoxicity and developmental neurotoxicity (DNT) studies. However, HED’s Hazard and 

Science Policy Council (HASPOC) concluded that the immunotoxicity study is not required. An 

immunotoxicity study is not anticipated to provide a lower point of departure (POD) or result in 

a more sensitive endpoint than those already used. Additionally, EPA has determined that DNTs 

for pyrethroid insecticides do not adequately characterize potential susceptibility of the young. 

Therefore, registrants who have not fulfilled requirements for the DNT study may instead cite six

previously-submitted pyrethroid DNT studies, rather than conduct a new study.

Prallethrin has been evaluated for a variety of toxic effects in experimental toxicity studies. 

Neurotoxicity was observed throughout the database, and effects were seen across species, sexes, 

and routes of administration. Effects were also observed in the liver (rats, mice, and dogs), heart 

(dogs), thyroid gland (rats), and kidney (mice and rats). However, neurotoxicity was the most 

sensitive endpoint in the toxicology database, and other effects were generally seen in the 

presence of neurotoxicity and/or at higher doses. The endpoints and PODs selected for risk 

assessment are based on neurotoxicity in a number of species and are protective of the toxic 

effects observed in the database. Literature studies indicate a possibility of increased sensitivity 

in juvenile rats to the neurotoxic effects of pyrethroid insecticides. In light of the literature 

studies, and pending receipt of additional information to better characterize potential sensitivity 
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of the young, an additional 3x Food Quality Protection Act (FQPA) Safety Factor (as estimated 

by pharmacokinetic modeling) has been applied to risk assessments for infants and children < 6

years old. Prallethrin is classified as “not likely to be carcinogenic to humans,” and there is no 

concern for mutagenicity.

For oral exposures (acute dietary and incidental oral), the endpoint and POD were selected from 

a chronic dog study in which neurotoxicity was observed within 4 weeks of dosing and was 

considered to have potentially resulted from a single dose, based on a weight of the evidence. 

For dermal assessment, the endpoint was selected from the route-specific 21-day dermal study in 

the rat, in which clinical signs were observed within 1 to 3 days of dosing. The endpoints being 

used to assess oral and dermal exposures are the same (neurotoxicity); therefore, risks from those 

routes of exposure were combined. Although the LOAEL for inhalation is also based on 

neurotoxicity, derivation of the human equivalent concentrations (HECs) used for inhalation risk 

assessment shows that assessing inhalation exposure based on the portal-of-entry effects is 

protective of the systemic endpoints, including neurotoxicity. As a result, inhalation exposure 

was not combined with either the dermal or the oral routes of exposure.

Acute lethality studies conducted with prallethrin indicate moderate acute toxicity via the oral 

and inhalation routes of administration (Category II) and low acute toxicity via the dermal route 

(Category IV). It is not irritating to the skin (Category IV), but is minimally irritating to the eye 

(Category IV). It is not a dermal sensitizer.

The toxicological profile of pyrethroids characterizes pyrethroids, including prallethrin, as being 

rapid in onset and associated with acute, peak exposures. Although the single day, acute studies 

for prallethrin do not provide the most sensitive PODs, neurotoxicity was observed in most of the 

repeat-dose toxicology studies within a few days of dosing. As such, the totality of the 

information suggests that only single day risk assessments need to be conducted for prallethrin. 

Based on the toxicity profile, HED will not conduct an intermediate or long-term exposure 

assessment for adults or children. A short-term exposure assessment is protective of exposures 

with longer durations.

Adequate residue data are available for the purpose of evaluating the proposed use of prallethrin 

as a mosquito adulticide over agricultural areas. Following application at a 10x exaggerated rate, 

the highest observed residue (0.045 ppm) was well below the 1.0 ppm tolerance associated with 

the FHE use.

The toxicological kinetic data for prallethrin demonstrate that it is not appropriate to assess 

chronic dietary risk for this insecticide due to a lack of increased toxicity with increased duration 

of exposure. However, the residential use sites for prallethrin and the patterns for exposure 

require estimates of chronic dietary (i.e. background from food and water) exposure in order to 

estimate aggregate risk.

Acute and chronic dietary exposure estimates were derived using the Dietary Exposure 

Evaluation Model (DEEM) with consumption data from the 2003-2008 National Health and 

Nutrition Examination Surveys (NHANES). The assessments were refined by incorporating 

anticipated residues from simulated warehouse residue trials and through the use of a percent 
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FHE treated value provided by the Biological and Economic Analysis Division (BEAD). 

Potential residues from the mosquito adulticide use were accounted for through the use of the 

maximum residue (acute exposure assessment) or average residue (chronic exposure assessment) 

from the adulticide residue trials. For the adulticide use, 100% crop treated was used for both 

the acute and chronic assessments. This value is considered to be an overestimate of the 

potential for the mosquitocide to drift onto growing crops. For drinking water, conservative 

modeled surface water concentrations generated with the FIRST Model were used. The acute 

dietary risk estimates for prallethrin are below HED’s level of concern (LOC) for all population 

subgroups, including those comprised of infants and children. The acute risk estimate for the 

general U.S. population is 10% of the acute population adjusted dose (aPAD). The population 

subgroup with the highest acute dietary risk estimate is Children 1-2, which uses 76% of the 

aPAD. 

Residential handler scenarios, which represent the worst case of exposure for registered 

residential uses of prallethrin, were reevaluated with the most updated endpoints and PODs, as 

well as the most recent version of the Residential SOPs for risk assessment resulting in dermal 

and inhalation risk estimates greater than their respective LOCs (dermal MOE ≥ 100 and 

inhalation MOE ≥ 30) and are not of concern. Furthermore, all adult and child post-application 

exposure scenarios for mosquito adulticide vector control and other registered residential uses

resulted in risk estimates greater than their respective LOCs (adult dermal LOC = dermal MOE 

≥100; and child dermal and incidental oral LOC = MOE ≥300) and are not of concern.

The acute aggregate risk estimates are equivalent to the corresponding dietary (food plus water) 

risk estimates, which are not of concern. The short-term aggregate risk assessment is based on

residues in background dietary (food + drinking water) and residential uses for adults and 

children. The recommended residential exposures for use in the adult and child aggregate 

assessments result from post-application dermal and incidental oral (hand-to-mouth for children 

only) exposure resulting from use of prallethrin on turf. For adults, dermal post-application 

exposure was combined with background exposure from food and water. For children, dermal 

post-application exposure was combined with incidental oral (i.e., hand to mouth) and 

background exposure from food and water. The short-term aggregate risk estimates for adults 

and children are not of concern.

Occupational handler scenarios for aerial and truck-mounted fogger mosquito adulticide

applications resulted in dermal and inhalation MOEs greater than their respective LOCs (dermal 

MOE ≥ 100 and inhalation MOE ≥ 30) at the baseline level of personal protective equipment 

(PPE) (i.e., single layer clothing, socks, shoes, no gloves or respirator) and are not of concern. 

The Multicide product labels indicate that portable, motorized backpack equipment can be used 

to apply ultra-low volume (ULV) particle sprays. Currently, HED does not have unit exposure 

data to assess this handler scenario. Therefore, chemical-specific data to support this scenario 

are needed, and constitute a data gap. These data need to be submitted under the Part 158 data 

requirements (Guideline 875.1400). Dermal post-application exposure resulted in MOEs 

significantly greater than the LOC (MOE ≥ 100) and are not of concern. Based on the Agency’s 

current practices, a quantitative post-application inhalation exposure assessment is not being 

performed for prallethrin at this time. If new policies or procedures are put into place, the 
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Agency might revisit the need for a quantitative occupational post-application inhalation 

exposure assessment for prallethrin.

Prallethrin was included in a cumulative risk assessment for pyrethrins and pyrethroids

(D394576, K. Whitby, 10/4/2011). In the cumulative assessment, residential exposure was the 

greatest contributor to the total exposure. The proposed new uses will contribute minimal 

additional exposure and risk to the overall cumulative assessment. Furthermore, HED evaluated 

an existing turf use of prallethrin to determine its contribution to the overall cumulative 

assessment. Neither the proposed new uses nor the currently registered turf use will have an

impact on the residential component of the cumulative risk estimates. Dietary exposures made a 

minor contribution to total pyrethroid exposure in the 2011 cumulative risk assessment. The 

dietary exposure assessment performed in support of the pyrethroid cumulative was much more 

highly refined than that performed for the single chemical. In addition, for the prallethrin risk 

assessment, the most sensitive apical endpoint in the prallethrin database was selected to derive 

the POD. Additionally, the POD selected for prallethrin is specific to prallethrin, whereas the 

POD selected for the cumulative assessment was based on common mechanism of action data 

that are appropriate for all 20 pyrethroids included in the cumulative assessment.

There are no human health risk concerns associated with the proposed label amendment. The 

established tolerance of 1.0 ppm for the use of prallethrin in FHEs is adequate to cover residues 

that might occur as a result of the mosquito adulticide use.

Potential areas of environmental justice concerns were considered in this human health risk 

assessment to the extent possible. An assessment was performed to estimate residues resulting 

from mosquito adulticide vector control for individuals in treated areas and addresses community 

exposures. The assessment resulted in no risks of concern. For more information, see Section 

3.5: Considerations of Environmental Justice.

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

intentionally exposed to a pesticide or other chemical. Those studies are subject to ethics review, 

have received that review, and are compliant with applicable ethics requirements.

2.0 HED Recommendations

HED does not object to the proposed label amendment expanding the use of prallethrin to the 

airspace above agricultural areas to control mosquitoes above and adjacent to these areas.

2.1 Data Deficiencies/Conditions of Registration

Since the estimated residential turf post-application exposure for residential turf using default 

turf transferable residue (TTR) values for prallethrin is not minimal in comparison to the LOC

(i.e., the calculated MOE is not greater than 10 times higher than the LOC, MOE = 900 

compared to the LOC of 3000, future refinements of this post-application exposure for 

prallethrin might be necessary due to increased use of prallethrin or advances in EPA risk 

assessments. Therefore, EPA is requiring the 40 CFR TTR data requirement to facilitate any
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necessary exposure assessment refinement and to further EPA’s general understanding of the 

availability of turf transferable pesticide residues.

The Multicide product labels indicate that portable, motorized backpack equipment can be used 

to apply ULV particle sprays. Currently, HED does not have unit exposure data to assess this 

handler scenario. Therefore, chemical-specific data to support this scenario are needed, and 

constitute a data gap. These data need to be submitted under the Part 158 data requirements 

(Guideline 875.1400).

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

A method based on gas chromatography with electron capture detection (GC/ECD), ID #262, is 

adequate for the enforcement of tolerances for residues of prallethrin in or on crop commodities. 

The reported limits of quantitation (LOQs) are 0.01 to 0.10 ppm, depending on the commodity. 

The limits of detection (LODs) were reported to be 0.004 to 0.06 ppm, depending on the 

commodity. 

Multiresidue methods testing for prallethrin has not been conducted, and is not required, based 

on previous Agency discussions with the petitioner on 11/3/2010. 

2.2.2 International Harmonization

There are no Codex or Canadian maximum residue limits (MRLs) for prallethrin. As a result, 

there are no harmonization issues for the chemical with respect to either the residue definition or 

MRLs.

2.2.3 Recommended Tolerances

Currently, a tolerance of 1.0 ppm is established for residues of the insecticide in or on food 

commodities in food handling establishments where food and food products are held, processed, 

prepared, and/or served. The tolerance does not need to be increased for the proposed label 

amendment expanding the mosquito adulticide use; however, the tolerance expression needs to 

be modified as discussed below.

Note to RD: HED recommends that the title/header for 40CFR §180.545 be amended from 

“Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1 RS)- cis, trans -

chrysanthemate; tolerances for residues.” to “Prallethrin; tolerances for residues.” to reflect 

the format in which essentially all other title/headers for citations 40CFR §180.101 through

40CFR §180.671 are stated. 

HED recommends that the petitioner submit a revised Section F for the proposed amended 

paragraph to be cited under 40CFR §180.545[a][1], referring to prallethrin by the CAS name, 2-

methyl-4-oxo-3-(2-propyn-1-yl)-2-cyclopenten-1-yl-2,2-dimethyl-3-(2-methyl-1-propen-1-
Prallethrin Human Health Risk Assessment DP No. D420116

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yl)cyclopropanecarboxylate, instead of the currently used name, (RS)-2-methyl-4-oxo-3-(2-

propynyl)cyclopent-2-enyl(1RS)-cis,trans-chrysanthemate.

HED recommends that the tolerance expression for prallethrin, cited under 40CFR 

§180.545[a][1], be amended to read as follows: 

A tolerance of 1.0 ppm is established for residues of the insecticide prallethrin, 

including its metabolites and degradates, in or on all raw agricultural commodities 

and processed food from use of prallethrin in food handling establishments where 

food and food products are held, processed, prepared and/or served, or as a widearea mosquito adulticide. Compliance with the tolerance level specified is to be 

determined by measuring only prallethrin, 2-methyl-4-oxo-3-(2-propyn-1-yl)-2-

cyclopenten-1-yl-2,2-dimethyl-3-(2-methyl-1-propen-1-

yl)cyclopropanecarboxylate. 

Additionally, HED recommends that RD delete 40CFR §180.545[a][2], 40CFR §180.545[a][3], 

and 40CFR §180.545[a][4]. 40CFR §180.545[a][2] should be deleted because it is being 

replaced by 40CFR §180.545[a][1], above. Parts [3] and [4] can be deleted because these parts 

are use directions that are not necessary or needed in the 40CFR listing for prallethrin. 

2.2.4 Revisions to Petitioned-For Tolerances

There is no revision to the petitioned-for tolerance.

2.3 Label Recommendations

Multicide Flying Insect Killer 27471 (EPA Reg. No. 1021-1710) has a separate occupational and 

residential use section on the registered label. HED’s updated assessment of the residential 

exposure scenarios using the revised Residential SOPs resulted in risks of concern. In an effort 

to mitigate these residential risks of concern, the registrant agreed to remove the residential use 

section from the label. The Registration Division (RD) should ensure that the residential use 

section of the label for Multicide Flying Insect Killer 27471 (EPA Reg. No. 1021-1710) is 

removed and that all references for use in kitchens are removed. 

3.0 Introduction

3.1 Chemical Identity
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TABLE 3.1. Prallethrin Nomenclature

Chemical Structure

Common Name Prallethrin

Company Experimental Name Not Available

Molecular Formula C19H24O3

Molecular Weight 300.4 amu

IUPAC Name (RS)-2-methyl-4-oxo-3-prop-2-ynylcyclopent-2-enyl (1RS,3RS;1RS,3SR)-2,2-

dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate

CAS Name 2-methyl-4-oxo-3-(2-propyn-1-yl)-2-cyclopenten-1-yl 2,2-dimethyl-3-(2-methyl1-propen-1-yl)cyclopropanecarboxylate

CAS Registry Number 23031-36-9

End-use Products (EP) Multicide Fogging Concentrate 2798, 0.075 lb ai/gal liquid formulation 

Multicide Fogging Concentrate 2922, 0.084 lb ai/gal liquid formulation

3.2 Physical/Chemical Characteristics

Prallethrin has very low water solubility (8.03 mg/L at 25oC) and a relatively high octanol/water

partition coefficient (log KOW = 4.49). These values account for the low surface and 

groundwater concentrations determined by the Environmental Fate and Effects Division’s 

(EFED’s) drinking water models, and indicate that the compound has potential to partition into 

fatty tissues. The chemical has a vapor pressure of 3.2 x 10-5 mm Hg at 25oC. See Appendix B

for a listing of additional physical and chemical properties.

3.3 Pesticide Use Pattern

Multicide Fogging Concentrate 2798 (EPA Registration #1021-1795), and Multicide Fogging 

Concentrate 2922 (EPA Registration #1021-2562) are currently registered for controlling public 

health pests in outdoor residential and recreational areas and in vegetation surrounding parks, 

woodlands, swamps, marshes, overgrown areas, and golf courses. The labels contain statements 

that prohibit use in areas that would potentially allow drift onto growing crops. MGK submitted 

a request to amend the labels by adding a statement that the products “may be applied over 

agricultural areas for the control of adult mosquitoes within or adjacent to these areas.”

Both Multicide products are formulated as liquid concentrates and contain 1% prallethrin, 5% 

sumithrin, and 5% piperonyl butoxide. This assessment only addresses the potential exposure 

associated with the proposed uses of prallethrin. Multicide 2798 contains 0.075 lbs per gallon of 

the active ingredient (ai) prallethrin, and Multicide 2922 contains 0.084 lbs ai per gallon. The 
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use directions on the labels are not changing as a result of the label amendment. The products 

are applied by aerial, ground, and handheld motorized equipment at a maximum application rate 

of 0.00072 lb ai per acre in a 24-hour period. Application rates are not to exceed 0.02 lbs ai per 

acre per year. These products are only to be applied by federal, state, tribal, or local government 

officials responsible for public health or adult mosquito control.

The PPE statements on the proposed labels require applicators and other handlers to wear longsleeved shirt and long pants, socks, and shoes. The proposed use directions are summarized in 

Table 3.3.a. The use rate specified on the proposed labels has not changed; therefore, the 

proposed labels reflect the existing rate, timing, and frequency of application.

Prallethrin is also registered for use in a variety of residential sites including homes, commercial 

settings, and FHEs. In addition, there are pet uses as well as outdoor uses for control of pests on 

turf. A residential assessment was performed in 1999. Since that time, the majority of the 

representative products have been cancelled (i.e., Evercide Carpet and Surface Spray 2655 –

Reg. No. 1021-1696; Flea Stop Linatoc Dip – Reg. No. 4758-163; and Permethrin Pet Plus 

Spray, EPA Reg. No. 4758-181) or the residential use has been removed from the product label 

(Multicide Flying Insect Killer 27471 Reg. No. 1021-1710). A summary of the remaining 

representative registered residential products and use sites with the highest application rates or 

percent ai is provided in Table 3.3.b. This table also includes a residential turf use (MGK 

Formula 2964 Microencapsulated Suspension Concentrate Insecticide - Reg. No. 1021-2574),

which is registered but was never previously assessed.

Table 3.3.a. Summary of Directions for Mosquito Adulticide Use of Prallethrin

Method of 

Application

Product and 

Formulation 

(Reg. No.)

Application 

Rate

(lb ai/A)

Maximum 

No. 

Applications 

per Season

Maximum 

Seasonal 

Application 

Rate

(lb ai/A)

PHI Use Directions, 

Application Timing, 

Type and Limitations

Aerial, Ground 

and Hand Held 

Equipment

Multicide 2798 

Reg. No 1021-

1795

(0.075 lb ai/gal)

Multicide 2922

Reg. No. 1021-

2562 

(0.084 lbs ai/gal)

0.00024 -

0.00072

lb ai/acre

(0.41 – 1.23 

fl oz/acre)

28 0.02 lb ai/acre 

in one year

NA

More frequent 

applications may be 

made to prevent or 

control a threat to 

public/animal health 

determined by a state, 

tribal, or local health or 

vector control agency.

Not for use in outdoor 

residential misting 

systems or meter 

released systems.
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3.4 Anticipated Exposure Pathways

Humans could be exposed to prallethrin residues from the following use scenarios: from 

consuming food treated in FHEs, from residential turf and indoor/outdoor spray uses, and from 

mosquito adulticide applications. The mosquito adulticide applications can result in prallethrin 

reaching surface and groundwater, both of which can serve as sources of drinking water. 

However, because of the low water solubility of the chemical and its affinity to bind to soil 

organic matter, drinking water concentrations will be very low. Occupational applicators can be 

exposed while handling the pesticide prior to application, mixing/loading the pesticide, and 

during application. Homeowners can be exposed dermally and via inhalation during mixing, 

loading, and applying non-restricted end-use products in residential settings. There is also 

potential for residential post-application exposure via inhalation, dermal, and incidental oral 

(children only) routes of exposure.

3.5 Consideration of Environmental Justice

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

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

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

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

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

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

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

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

Extensive data on food consumption patterns are compiled by the U.S. Department of 

Agriculture under the National Health and Nutrition Examination Survey, What We Eat in 

Table 3.3.b. Revised Registered Residential Handler Use of Prallethrin

Product and 

Formulation

Use Site Method of 

Application

Application 

Rate

(lb ai/A)

Use Directions, 

Application Timing, Type 

and Limitations

EVERCIDE® 

NYLAR Total 

Release Aerosol 

2644

(0.04% ai)

Reg. No. 1021-1656

(assessed in 1999)

Indoor Use 

(carpets, 

upholstery, 

floor cracks and 

cabinets)

Fogger 1 fogger/room

Do not use in room smaller 

than 5 ft x 5 ft. Vacate 

treated house immediately 

after application. Wait 2 

hours after application and 

then open window, vents,

and doors for 2 hours.

MGK Formula 2964 

Microencapsulated 

Suspension 

Concentrate 

Insecticide

(1.6% a.i.)

Reg. No. 1021-2574

Lawns, 

landscapes, 

ornamentals, 

and recreational 

parks and fields

Spray

0.045 lb ai/A or 

0.00011 lb ai/ 

gal

All outdoor applications 

are limited to crack and 

crevice treatment only,

except for applications to 

lawns, which may be 

treated as broadcast.
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America, (NHANES/WWEIA). These food consumption patterns are used in pesticide risk 

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

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

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

exposure assessments are performed when conditions or circumstances warrant. Whenever 

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

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

post-application are evaluated. A residential post-application exposure assessment was 

performed to estimate potential exposure to residues resulting from mosquito adulticide 

applications to individuals in treated areas. Exposure risk estimates were not of concern. 

Further considerations are currently in development, as OPP has committed resources and 

expertise to the development of specialized software and models that consider exposure to 

bystanders and farm workers as well as lifestyle and traditional dietary patterns among specific 

subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Prallethrin is a member of the pyrethroid class of insecticides. Pyrethroids have historically been 

classified into two groups, Type I and Type II, based upon chemical structure and 

neurotoxicological effect. Type I pyrethroids lack an alpha-cyano moiety and induce a syndrome 

consisting of aggressive sparring, altered sensitivity to external stimuli, and fine tremor 

progressing to whole-body tremor and prostration in rats. These Type I pyrethroid-specific 

behaviors are collectively described as the T-syndrome. Type II pyrethroids contain an alphacyano moiety and produce a syndrome that includes pawing, burrowing, salivation, and coarse 

tremors leading to choreoathetosis in rats. These Type II pyrethroid-specific behaviors are 

collectively described as the CS-syndrome (Verschoyle and Aldridge 1980; Lawrence and 

Casida 1982). Prallethrin is structurally similar to Type I pyrethroids. The adverse outcome 

pathway (AOP) shared by pyrethroids involves the ability to interact with voltage-gated sodium 

channels (VGSCs) in the central and peripheral nervous system, leading to changes in neuron 

firing, and ultimately neurotoxicity (Figure 4.0). 

Figure 4.0. Adverse outcome pathway for pyrethroids

Target 

Tissue 

Dose

VGSC 

Alterations

In Vivo 

Clinical 

Signs

Altered 

Neuronal

Excitability
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4.1 Toxicology Studies Available for Analysis

The database of experimental toxicology studies available for prallethrin provides a robust 

characterization of the hazard potential for children 6 years old and older as well as for adults. 

The data from the following studies were used to evaluate the hazard potential of prallethrin:

-WIL Laboratory Acute Oral Study in the Rat 

-21 Day Dermal Study in the Rat 

-90 Day Oral Studies in the Rat, Mouse, and Dog

-Chronic/Carcinogenicity Studies in the Rat, Mouse, and Dog 

-Developmental Studies in the Rat and Rabbit

-Reproduction Study in the Rat 

-Acute and Subchronic Neurotoxicity Studies in the Rat

-Mutagenicity Battery of Studies

-28 Day Subchronic Inhalation Study

An immunotoxicity study is not available for consideration as required under the Part 158 

toxicology data requirements. However, HED’s Hazard and Science Policy Council (HASPOC) 

concluded that the study is not required for prallethrin. An immunotoxicity study is not 

anticipated to provide a lower POD or result in a more sensitive endpoint than those already used

(TXR No. 0056830). A developmental neurotoxicity study (DNT) study is not available for 

prallethrin. However, EPA has determined that DNTs for pyrethroid insecticides do not 

adequately characterize potential susceptibility of the young. Therefore, registrants who have 

not fulfilled requirements for the DNT may instead cite six previously-submitted pyrethroid 

DNT studies, rather than conduct a full new study. 

The studies available for consideration of toxicity provide a comprehensive database for 

prallethrin. The WIL study is an acute oral non-guideline study that measures functional 

observational battery (FOB) activity in rats that were treated acutely with various pyrethroids. In 

addition, numerous studies from the scientific literature conducted over several decades describe 

the pharmacodynamic and pharmacokinetic profile of the pyrethroids in general. This scientific 

literature has been recently reviewed by several groups (Soderlund et al. 2002; Shafer et al., 

2005; Wolansky and Harrill 2008). A literature study is also available that measures motor 

activity after pyrethroid exposure for a number of pyrethroid chemicals (Wolansky et al. 2006). 

However, prallethrin was not included in the study. 

In addition, there are ongoing efforts to develop data to inform the potential sensitivity of infants 

and younger children to pyrethroids as a class (see Section 4.4). Despite these scientific efforts, 

HED is confident that it has chosen points of departure and uncertainty factors in this risk 

assessment that are health protective and have a strong scientific foundation.

4.2 Toxicological Profile

Prallethrin has been evaluated for a variety of toxic effects in experimental toxicity studies. 

Neurotoxicity was observed throughout the database and is the most sensitive endpoint. Effects 

were seen across species, sexes, and routes of administration. In the acute rat neurotoxicity 
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study, decreased exploratory behavior was seen at the time of peak effect (2 hrs). Reduced 

motor activity and transient tremors were also observed in the study. In the subchronic rat 

neurotoxicity study, a higher arousal rate was observed in animals at the highest dose tested. 

Clinical signs of neurotoxicity were also observed in other toxicity studies (subchronic and 

chronic oral studies in dogs, developmental toxicity studies in the rat and rabbit, 21-day dermal 

and 28-day inhalation studies in rats). No neurotoxic effects were observed in rats in the chronic 

toxicity study. 

Effects were also observed in the liver (rats, mice, and dogs), heart (dogs), and thyroid gland 

(rats). Some effects were also seen in the kidney (mice and rats). However, neurotoxicity was 

the most sensitive endpoint in the toxicology database, and other effects were generally seen in 

the presence of neurotoxicity and/or at higher doses. Liver effects observed included increased 

weight, elevated serum cholesterol and alkaline phosphatase activity, centrilobular hepatocyte 

vacuolation, histiocytic infiltration, enlarged liver, and perilobular hepatocellular hypertrophy. 

In dogs, myocardial fiber degeneration was seen in females in the subchronic study at the highest 

dose tested. Heart effects were also seen in one mid-dose female in the chronic study 

(hemorrhage and red discoloration). However, there was no dose response for the observed heart 

lesions in the study. Thyroid effects were observed in rats and consisted of increases in the 

number of small follicles and follicular cell hypertrophy and hyperplasia. The thyroid effects 

were seen in short-term studies in the presence of liver effects. Kidney effects observed were 

increased weights and histopathology. 

Developmental and reproduction studies are available for prallethrin. There was no evidence of 

increased quantitative or qualitative susceptibility in any of the studies. In the developmental 

studies, no toxic effects were noted in fetuses up to the highest doses tested. Maternal effects in 

the studies included tremors, salivation, exaggerated reflexes, and chromorhinorrhea. In the 

reproduction study, decreased pup body weights were seen during the lactation period. Effects 

seen in parental animals were decreased body weights and body weight gains, increased liver 

weights and microscopic findings in the liver, kidney, thyroid, and pituitary.

Prallethrin is classified as “not likely to be carcinogenic to humans.” No tumors were observed 

in rat and mouse carcinogenicity studies up to the highest doses tested. In both the rat and mouse 

studies, the animals could have tolerated higher dose levels; however, HED determined that dose 

levels were adequate to assess potential carcinogenicity.

Prallethrin tested negative in the majority of the genotoxicity studies. It also tested negative in 

an in vitro chromosomal aberration study in Chinese Hamster Ovary (CHO K1) cells without 

metabolic activation, but tested positive at all doses with metabolic activation. However, 

clastogenicity was not clearly dose-related, was seen at nontoxic and slightly toxic doses, was 

not expressed in in vivo studies, and structure-activity comparisons with the other pyrethroids 

revealed no correlations with clastogenicity. Other gene mutation, chromosomal aberration, and 

unscheduled DNA synthesis (UDS) studies were negative. Therefore, there is no concern for 

genotoxicity.

Acute lethality studies conducted with prallethrin indicate moderate acute toxicity via the oral 

and inhalation routes of administration (Category II) and low acute toxicity via the dermal route 
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(Categories IV). It is not irritating to the skin (Category IV) but is minimally irritating to the eye 

(Category IV). It is not a dermal sensitizer.

Metabolism data are available for prallethrin. The pharmacokinetics for prallethrin are similar to 

those for other pyrethroids, i.e., rapid absorption and clearance. Metabolism studies in rats with 

the cis- and trans-isomers indicate that, with an oral dose of 2 or 100 mg/kg/day or with repeated 

oral doses of 2 mg/kg day, the cis- and trans- isomers are rapidly absorbed, distributed, 

metabolized, and excreted under all dosing regimens. Most of the radioactivity is recovered in 

the urine and feces within 48 hours for both males and females for both isomers. A much greater 

proportion of the administered dose of the trans-isomer was eliminated in the urine (45.2-58.1% 

administered dose [AD] for males, 52.1-62.1% AD for females) than was the cis-isomer (13.3-15.8% 

AD for males, 21-23.3% AD for females). This occurred as a result of easier cleavage of the ester 

linkage of the trans-isomer by esterase. For the rats administered the cis-isomer, urinary 

excretion was a minor route compared to fecal excretion. Females excreted a greater proportion 

of the radioactivity in the urine than did males for both isomers. Bioaccumulation and retention 

of the cis- and trans-isomers are low. Based on the metabolites identified, the major 

biotransformation reactions of the cis- and trans-isomers include: (1) oxidation at the methyls of 

the isobutenyl group in the acid moiety and at the C-1 or C-2 positions of the propynyl group in 

the alcohol moiety; (2) cleavage of the ester linkage; (3) conjugation of hydroxy derivatives with 

glucuronic acid and sulfuric acid.

 

4.3 Pyrethroid Pharmacokinetic and Pharmacodynamic Profile

The extensive body of scientific literature on the pyrethroids provides insight into the 

contributions of pharmacokinetics (PK) and pharmacodynamics (PD) to the general toxicity 

profile of this class of chemicals. This information also provides valuable insight into the 

potential age-related differences in toxicity for the pyrethroids. The following sections discuss 

the specific issues related to pyrethroid pharmacokinetics, pyrethroid pharmacodynamics, and 

age-related differences in pyrethroid toxicity.

4.3.1 Pharmacokinetics

Pharmacokinetics (PK) can be defined as what the body does to the chemical; in this case, how 

pyrethroids are distributed and eliminated following exposure. Specific to pyrethroids, PK refers 

to the process(es) that determine the concentration of the pyrethroids reaching sodium channels. 

The underlying pharmacokinetics of pyrethroids is an important determination of their toxicity 

because the concentration of pyrethroid at the sodium channel relates to the extent of toxicity; 

greater pyrethroid concentration translates as increased neurotoxicity. Physiological processes 

that significantly contribute to the PK include metabolism, protein binding, and partitioning. 

Carboxylesterases and cytochrome P450 enzymes are the two major enzyme families responsible 

for the metabolism of pyrethroids. It is the ontogeny of these enzymes that accounts for the agerelated sensitivity observed after pyrethroid exposures. However, pyrethroid residues in fatty 

tissue are not available to interact with the VGSCs in vital tissues and, therefore, do not 

contribute to overall toxicity. 
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In 2011 the Agency conducted an analysis of the toxicokinetic profile of pyrethroids. Several 

studies in this analysis indicate that there are age-dependent pharmacokinetic differences for the 

pyrethroids (i.e., there are differences in the ability of adults and juveniles to metabolize 

pyrethroids). The enzymes that metabolize and detoxify the pyrethroids are present in rats and 

humans at birth (Koukouritaki et al. 2004; Yang et al. 2009). As a result, both juveniles and 

adults are able to tolerate low doses of pyrethroids when the internal dose, or the amount of 

pyrethroid at the sodium channel, is low. However, the activity of these enzymes increases with 

age, conveying in adults a greater capacity to detoxify pyrethroids compared to juveniles (Anand 

et al. 2006; de Zwart et al. 2008; Yang et al. 2009). For example, the rate of in vitro metabolism 

of deltamethrin by plasma carboxyesterases, plus hepatic carboxyesterases and cytochrome 

P450s (microsomes) is at least 6 times as high for PND 90 rats as for PND 10 rats (Anand et al. 

2006). As a consequence, higher internal doses (i.e., those associated with high doses in 

experimental toxicology studies) overwhelm the clearance mechanisms in juveniles, but because 

adults have greater enzyme activity, they are able to tolerate higher doses prior to the onset of 

toxicity. As a matter of perspective, the anticipated exposures from typical dietary or residential 

activities are not expected to overwhelm the premature metabolic systems in juveniles. 

Predictive PBPK models have recently been developed to describe the PK of a few pyrethroids 

(Mirfazaelian et al. 2006; Godin et al. 2010). Among these is an age-dependent model 

developed by the Agency that is capable of predicting the concentration of deltamethrin in the 

brains of rats at multiple ages (Tornero-Velez et al. 2010). The brain is considered the primary 

target organ for pyrethroids, and increased pyrethroid concentrations are correlated with 

increasing systemic toxicity. This model predicts that, compared to adult rats (i.e., 90 days old), 

equivalent brain concentrations of deltamethrin would be achieved with a 3.8x fold lower oral 

dose in 10-day old rats and 2.5x lower dose in 21-day old rats (Tornero-Velez et al. 2010). For 

example, a 1 mg/kg dose in the adult is equivalent to a 0.26 mg/kg dose (≈1 mg/kg ÷ 3.8mg/kg) 

in the 10-day old rats and to a 0.4 mg/kg (≈1 mg/kg ÷ 2.5mg/kg) dose in a 21-day old rat. The 

difference between a 3.8- and a 2.5-fold dose is within background variability of the model. As a 

result, the Agency concludes that juvenile rats are three times as sensitive as adults with respect 

to pyrethroid pharmacokinetics. Therefore, the pharmacokinetic contribution to the FQPA factor 

will be 3x.

4.3.2 Pharmacodynamics

Pharmacodynamics (PD) can be defined as the changes that chemicals cause to the body, in this 

case, how pyrethroids interact with the sodium channels. Substantial evidence from in vitro and 

in vivo studies support the AOP illustrated in Figure 4.1 and the disruption of sodium channels 

by pyrethroids as an early key event (Lund and Narahashi 1982; Salgado et al. 1989; Song and 

Narahashi 1996; Tabarean and Narahashi 1998; Soderlund et al. 2002 (review)). With respect to 

altered neuronal excitability, Type I pyrethroids cause slight prolongations of the sodium current 

tails (e.g., ~20 ms), often resulting in long trains of action potentials. In contrast, Type II 

pyrethroids significantly prolong sodium current tails (e.g., 200 ms to minutes) typically 

resulting in increased resting membrane potential and ultimately causing depolarization 

dependent action potential block. Choi and Soderlund (2006) examined interactions of several 

pyrethroids with mammalian VGSCs expressed in Xenopus oocytes. 
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HED would prefer to use an early key event in the AOP for pyrethroids in selection of PODs. 

However, in vivo measures of VGSC alteration and altered neuronal excitability are not readily 

available for use in risk assessment at this time, and approaches for extrapolating in vitro

findings such as those discussed here to in vivo measures are not yet developed. Therefore, the 

Agency is focusing its efforts in hazard characterization and identification on the apical endpoint 

(i.e., changes in neurobehavior in laboratory animals). Neurotoxicity resulting from pyrethroids 

is generally characterized by tremors, hyper- or hypothermia, heightened response to stimuli, 

salivation, tremors and convulsions (Soderlund et al. 2002; Wolansky and Harrill 2008; Weiner 

et al. 2009). 

In contrast to the age-related PK differences identified in the 2011 analysis, PD contributions to 

pyrethroid toxicity are not age-dependent even though there are several variations of sodium 

channels, called isoforms, that are differentially expressed by tissue and age. Because of the 

nature of the interaction of pyrethroids with sodium channels, it is difficult to obtain dynamic 

information in vivo. To date, a readily useable biomarker of in vivo pyrethroid interaction with 

sodium channels has not been identified, making it impractical to determine the isoform 

combinations that are present and being acted upon by pyrethroids. Therefore, much of the 

information available to the Agency to characterize the PD relationship between pyrethroids and 

sodium channels has been derived from in vitro studies using frog oocytes or neuronal cells 

cultured in defined media. These in vitro techniques do not provide a direct quantitative measure 

of in vivo pyrethroid activity. However, these techniques consistently and qualitatively 

demonstrate that channel isoforms expressed in juveniles are not more sensitive to pyrethroid 

perturbation compared to isoforms expressed in adults and that, pharmacodynamically, the rat is 

a conservative model for humans. For example, Meacham et al. (2008), compared the sensitivity 

to deltamethrin of an adult isoform and a juvenile isoform expressed in frog oocytes. The 

isoforms had comparable responses at environmentally relevant concentrations (<500 nM) of 

deltamethrin, suggesting a lack of PD difference between juveniles and adults at low exposure 

levels. In addition, a study directly comparing a homologous rat and human VGSC isoform, 

NaV1.3, revealed that the rat isoform was 4-fold more sensitive than the equivalent human 

sodium channel to the pyrethroid tefluthrin (Tan and Soderlund 2009). These data suggest that 

the rat is a highly sensitive model, and extrapolations from the rat would be protective of human 

health. The occurrence and ontogeny of voltage-gated sodium channels in humans is not well 

characterized compared to the rat. However, based on the comparable function and distribution 

of sodium channels between the species, the rat is an appropriate surrogate for the evaluation of 

human PD (Goldin et. al. 2000; Goldin 2002). As a result, the Agency concludes that juvenile 

rats are not more sensitive than adults with respect to pyrethroid pharmacodynamics. Therefore, 

the pharmacodynamic contribution to the FQPA factor will be 1x.

4.3.3 Critical Duration of Exposure

One of the key elements in risk assessment is the appropriate integration of temporality between 

the exposure and hazard assessments. For prallethrin, neurotoxicity is the most sensitive 

endpoint, with effects being observed within the first few days of dosing. Effects were also 

observed in the liver (rats, mice, and dogs), heart (dogs), and thyroid gland (rats). Some effects 

were also seen in the kidney (mice and rats). However, the effects were generally seen in the 
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presence of neurotoxicity or at higher doses. Thus, endpoints selected for neurotoxicity are 

protective for effects observed in the toxicity database. 

Consistent with the mode of action, in general, onset of neurotoxicity following an acute 

pyrethroid dose is rapid, with a time to peak effect for neurobehavioral effects ranging from 4 to 

8 hours (Wolansky and Harrill 2008; Weiner et al. 2009; Scollon et al. 2011). Furthermore, 

rapid metabolism and elimination preclude accumulation and increased potency following 

repeated dosing. Therefore, for most pyrethroids, the acute toxicity studies typically demonstrate 

neurotoxicity at doses lower than doses in other studies. However, the available single dose, 

acute studies (i.e., the WIL FOB study) and the acute neurotoxicity (ACN) study) for prallethrin 

did not provide the PODs. In fact, the PODs from the WIL FOB and ACN studies are 

approximately 10-fold higher than PODs from other studies where neurotoxicity was observed. 

It is notable that both acute gavage studies used relatively high vehicle volumes of 5 and 10 

mL/kg, respectively. For some pyrethroids, the gavage volume can play an important role in 

potency because the volume impacts the absorption characteristics (e.g., timing, amount) 

(Crofton et al, 1995). In the prallethrin studies, it is plausible that the relatively high corn oil 

volume causes a reduction in the peak level of prallethrin in the brain; thereby increasing the 

POD. 

As noted in Table 4.3.3, when comparing the Human Equivalent Doses (HEDs) for the 

developmental rat study, subchronic neurotoxicity study (SCN), and two dog studies, there is 

striking consistency across species and duration. In the studies, neurotoxicity was generally 

observed during the first few days or first week of the study, hours after dosing. 

The weight of evidence from the available guideline, non-guideline, mechanism of action, and 

pharmacokinetics studies supports characterizing the toxicological profile of pyrethroids, 

including prallethrin, as being rapid in onset and associated with acute, peak exposures. 

Although the single day, acute studies for prallethrin do not provide the most sensitive PODs, 

neurotoxicity was observed in most of the repeat-dose toxicology studies within a few days of 

dosing. As such, the totality of the information suggests that only single day risk assessments 

need to be conducted for prallethrin.
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* day neurotoxicity initially observed

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

The prallethrin toxicity database includes developmental toxicity studies in the rat and rabbit, 

and a reproduction study in the rat. No evidence of increased qualitative or quantitative 

susceptibility was noted in any of these studies. This lack of susceptibility is consistent with the 

results of guideline developmental and reproduction studies with other pyrethroid pesticides.

High-dose LD50 studies (studies assessing what dose results in lethality to 50 percent of the 

tested population) in the scientific literature indicate that pyrethroid exposure can result in 

increased quantitative sensitivity in the young, specifically in the form of neurotoxicity. 

Examination of pharmacokinetic and pharmacodynamic data indicates that the sensitivity 

observed at high doses is related to pyrethroid age-dependent pharmacokinetics - the activity of 

enzymes associated with the metabolism of pyrethroids. With otherwise equivalent administered 

doses for adults and juveniles, predictive pharmacokinetic models indicate that the differential 

adult-juvenile pharmacokinetics will result in a 3x greater dose at the target organ in juveniles 

compared to adults. No evidence of increased quantitative or qualitative susceptibility was seen 

in the pyrethroid scientific literature related to pharmacodynamics (the effect of pyrethroids at 

the target tissue) both with regard to interspecies differences between rats and humans and to 

differences between juveniles and adults. Specifically, there are in vitro pharmacodynamic data 

and in vivo data indicating similar responses between adult and juvenile rats at low doses and 

Table 4.3.3. Points of Departure with Neurological Effects for Toxicology Studies with Prallethrin

Study MRID Duration

Study findings

NOAEL 

(mg/kg/day)

LOAEL 

(mg/kg/day)

3⁄4 Body Weight 

Adjustment for HED 

Comparison

NOAEL LOAEL

WIL Laboratories FOB 

study Rat(Gavage-5mL/kg 

corn oil)

48333801 Acute, single 

exposure

150 250 --- ---

Acute Neurotoxicity Rat 

(Gavage-10mL/kg corn 

oil)

43343301 Acute, single 

exposure

100 300--- ---

Developmental Rat 

(Gavage-0.5% 

methylcellulose)

42030905 10 days

*GD9&10 10 30 2.91 8.72

Subchronic Neurotoxicity 

Rat

(Dietary)

43694501 90 days *wk12 9.3 74 2.70 21.51

Subchronic Dog (Capsule) 41321817 90 days

*wk1 3 10 1.84 6.15

Chronic Dog

(Capsule)

42077002 1 year

*wk 4 2.5 5 1.54 3.07
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data indicating that the rat is a conservative model compared to the human based on speciesspecific pharmacodynamics of homologous sodium channel isoforms in rats and humans.

In light of the literature studies indicating a possibility of increased sensitivity in juvenile rats at 

high doses, EPA is retaining a 3x additional safety factor as estimated by pharmacokinetic 

modeling for infants and children less than 6 years old. For several reasons, EPA concludes 

there are reliable data showing that a 3x factor is protective of the safety of infants and children. 

First, the high doses that produced juvenile sensitivity in the literature studies are well above 

normal dietary or residential exposure levels of pyrethroids to juveniles, and these lower levels 

of exposure are not expected to overwhelm the ability to metabolize pyrethroids, as occurred 

with the high doses used in the literature studies. This conclusion is confirmed by the lack of a 

finding of increased sensitivity in the majority of the pre- and post-natal guideline studies for 

pyrethroids, despite the relatively high doses used in those studies. Second, the portions of the 

uncertainty factors that account for potential pharmacodynamic differences are likely to 

overestimate the risk of inter- and intraspecies pharmacodynamic differences, given the data 

showing similarities in pharmacodynamics between juveniles and adults and between humans 

and rats. For the FQPA Safety Factors, the pharmacodynamic portions are generally considered 

to be 3x; however, for pyrethroids, it is reduced to 1x because no differences among the various 

groups are observed. Finally, as indicated, pharmacokinetic modeling only predicts a 3x

difference between juveniles and adults.

The information described above is summarized in Re-Evaluation of the FQPA Safety Factor for 

Pyrethroid Pesticides (D381210, E. Scollon, A. Lowit, 6/27/2011). 

4.4.1 Completeness of the Toxicology Database

The toxicology database for prallethrin is considered complete with respect to guideline toxicity 

studies for prallethrin. However, the Agency lacks additional information to fully characterize 

the potential for juvenile sensitivity to the neurotoxic effects of pyrethroids. The toxicity 

database for prallethrin does include studies that can be used to characterize most effects, 

including potential developmental and reproductive toxicity and neurotoxicity. Acceptable 

developmental toxicity studies in rats and rabbits, a reproduction study in rats, and neurotoxicity 

studies (ACN, and SCN) in rats are available. In addition, route-specific dermal and inhalation 

studies are available. The prallethrin database lacks acceptable immunotoxicity and 

developmental neurotoxicity (DNT) studies. However, HED’s Hazard and Science Policy 

Council (HASPOC) concluded that the immunotoxicity study is not required. An 

immunotoxicity study is not anticipated to provide a lower POD or result in a more sensitive 

endpoint than those already used (TXR No. 0056830). Additionally, EPA has determined that 

DNTs for pyrethroid insecticides do not adequately characterize potential susceptibility of the 

young. In 2009, EPA stated that registrants who have not fulfilled requirements for the DNT 

may instead cite six previously-submitted pyrethroid DNT studies, rather than conduct a full new 

study.
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4.4.2 Evidence of Neurotoxicity

Like other pyrethroids, prallethrin causes neurotoxicity by interacting with sodium channels 

leading to clinical signs of neurotoxicity. Neurotoxicity typical of pyrethroids was observed in 

several of the toxicity studies for the active ingredient. These effects are assessed by the 

available guideline and non-guideline studies.

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

Based on the prallethrin-specific data, there is no indication of increased juvenile sensitivity. 

However, after reviewing the extensive body of data and peer-reviewed literature on 

pyrethroids, the Agency has reached a number of conclusions regarding fetal and juvenile 

sensitivity for pyrethroids, including the following:

Based on an evaluation of over 70 guideline toxicity studies for 24 pyrethroids submitted to the 

Agency, including prenatal developmental toxicity studies in rats and rabbits, and pre- and 

postnatal multi-generation reproduction toxicity studies and DNTs in rats in support of 

pyrethroid registrations, there is no evidence that pyrethroids directly impact developing 

fetuses. None of the studies show any indications of fetal toxicity at doses that do not cause 

maternal toxicity. 

 The developmental and reproduction studies for prallethrin did not demonstrate 

susceptibility of the young or developing animal, which is consistent with the majority 

of the pyrethroid database. However, increased susceptibility was seen in offspring 

animals in DNT studies with another pyrethroid, zeta-cypermethrin (decreased pup body 

weights) and in DNT and reproduction studies with beta-cyfluthrin (decreased body 

weights and tremors). The reductions in body weight and the other non-specific effects 

observed occurred at higher doses than neurotoxicity, the effect of concern for 

pyrethroids. Overall, findings of increased sensitivity in juvenile animals in pyrethroid 

studies are rare. Therefore, the residual concern for the postnatal effects seen in the 

studies is reduced.

 Increased susceptibility was seen in offspring animals in the DNT study with the 

pyrethroid zeta-cypermethrin (decreased pup body weights) and DNT and reproduction 

studies with another pyrethroid beta-cyfluthrin (decreased body weights and tremors). 

However, the reductions in body weight and the other non-specific effects occur at higher 

doses than neurotoxicity, the effect of concern for pyrethroids. The available 

developmental and reproduction guideline studies in rats with zeta-cypermethrin did not 

show increased sensitivity in the young to neurotoxic effects. Overall, findings of

increased sensitivity in juvenile animals in pyrethroid studies are rare. Therefore, the 

residual concern for the postnatal effects is reduced.

 High-dose LD50 studies in the scientific literature indicate that pyrethroids can result in 

increased quantitative sensitivity to juvenile animals. Examination of pharmacokinetic 

and pharmacodynamic data indicates that the sensitivity observed at high doses is 

related to age-dependent pyrethroid pharmacokinetics. Furthermore, a rat PBPK model 
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predicts a 3-fold increase of pyrethroid concentration in juvenile brains compared to 

adult brains at high doses.

 In vitro pharmacodynamic data and in vivo data indicate that adult and juvenile rats have 

similar responses to pyrethroids at low doses and, therefore, juvenile sensitivity is not 

expected at relevant environmental exposures. Further, data also show that the rat is a 

conservative model compared to the human based on species-specific 

pharmacodynamics of homologous sodium channel isoforms. 

Additional in vitro and in vivo studies are currently being conducted that could potentially inform 

a number of issues related to pyrethroid toxicity as a class. In 2010, the Agency requested 

proposals for study protocols that could identify and quantify potential juvenile sensitivity. The 

Agency received a single, coordinated response from the Pyrethrin and Pyrethroids Working 

Group (PPTWG), a conglomerate of pyrethroid registrants. The PPTWG protocol was reviewed 

during a July 2010 FIFRA SAP meeting. Based on comments from the SAP, the initial study 

proposal was refined. At the present time, pesticide registrants and product formulators have 

come together as the Council for the Advancement of Pyrethroid Human Risk Assessment 

(CAPHRA) and plan on doing the following: 1) conducting in vitro studies demonstrating the 

interaction of pyrethroids with exogenously expressed rat and human VGSCs; 2) conducting in

vitro studies demonstrating interaction of pyrethroids in rat neurolemma cells; 3) developing rat 

and human PBPK models, including additional pharmacokinetic data; and 4) conducting in vivo

behavioral testing using auditory startle testing in rats. As these data become available, the 

Agency will determine whether re-evaluation of the age-related sensitivity of pyrethroids is 

appropriate.

Although EPA is seeking additional data to further characterize the potential neurotoxicity for 

pyrethroids, EPA has reliable data that show that reducing the FQPA SF to 3X will protect the 

safety of infants and children less than 6 years old.

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties with regard to dietary exposure. The dietary exposure 

assessments are based on highly conservative residue levels for the mosquito adulticide use and 

for the FHE uses. Furthermore, conservative, upper-bound assumptions were used to determine 

exposure through drinking water and residential sources, such that these exposures have not been 

underestimated.

Although EPA has required additional data on transferable residues from treated turf for 

prallethrin, EPA is confident that it has not underestimated turf exposure due to the 

conservativeness of the default turf transfer value and conservative assumptions in the short-term 

turf assessment procedures (e.g., assuming residues do not degrade over the thirty day 

assessment period and assuming high-end activities on turf for every day of the assessment 

period). The additional data on turf transferable residues have been required in case refinement 

of exposure assessments is needed in the future and to further EPA’s general understanding of 

the availability of pesticide residues on turf.
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4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response and Hazard Assessment

The details for selecting toxicity endpoints and PODs are presented in Appendix A.3. Based on 

the proposed use patterns for prallethrin, the expected exposure profile will be for dietary, 

dermal, inhalation, and incidental oral exposures. Based on the toxicity profile, HED will not be 

conducting intermediate- or long-term exposure risk assessments for adults or children because 

the data do not demonstrate an increase in the severity of neurotoxic effects with increasing 

duration of exposure.

As previously indicated, the toxicity endpoints for prallethrin are consistently based on clinical 

signs of neurotoxicity consistent with pyrethroid neurotoxicity. The available studies include 

multiple species, study designs, and durations. Because uncertainty associated with the POD is 

propagated throughout the risk assessment, one of the key factors in POD selection is the 

robustness of the dose-response data. There is a special study available for a number of 

pyrethroids that measures motor activity (Wolansky et al, 2006) that is being used to derive 

PODs for some chemicals in this class. However, prallethrin was not one of the chemicals 

evaluated in the study. There are guideline experimental toxicology studies available for 

prallethrin that are of high quality. Additionally, data from another special study are available 

for prallethrin (MRID 48333801). WIL Laboratories performed this study to evaluate 

neurobehavioral outcomes. However, as discussed in Section 4.3.3, the WIL FOB study and the 

ACN study both used high vehicle volumes that likely impacted absorption characteristics of 

prallethrin, thereby increasing the POD. When using 3⁄4 body weight scaling to compare human 

equivalent doses for rat and dog studies showing neurotoxicity, they are generally very similar

(within 2x). However, the chronic dog study still provided a slightly lower POD. Therefore, the 

dog study was used for acute dietary and incidental oral risk assessments.

Acute Dietary: The chronic dog study was selected based on neurotoxic effects observed at the 

LOAEL of 5 mg/kg/day (NOAEL=2.5 mg/kg/day). For acute dietary risk assessment, the 

endpoint used is commonly based on adverse effects attributed to a single-dose exposure. 

However, for prallethrin, it is based on neurotoxic effects initially observed at 4 weeks. For 

pyrethroid chemicals, the pharmacokinetics indicate that the onset of neurotoxicity is rapid, with 

the time to peak effect for neurobehavioral effects occurring within hours. This is followed by 

rapid metabolism and elimination that does not result in accumulation. Therefore, repeated 

dosing is essentially a series of acute exposures, and the effects seen in the dog study after 4 

weeks are still appropriate for setting the acute reference dose (aRfD). 

In the dog study, animals were given a bolus dose (capsule) of prallethrin once daily for 52 

weeks. The dogs were observed daily for clinical signs and mortality. At 4 weeks, trembling 

was observed in one dog at the LOAEL of 5 mg/kg/day. Although trembling was observed in 

only one dog on one occasion at the 5 mg/kg/day dose, there was a clear dose response for the 

effect. In the same dog, convulsions and tremors were seen at week 19. Convulsions, panting, 

salivation, rapid eye blinking, and muscle twitching were seen 5 hours after dosing prior to the 

death of the dog during week 44. Based on the toxicity profile for pyrethroids, clinical signs 

would be expected sooner than 4 weeks; however, it could have been easily missed due to the 
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timing of the post-dosing clinical examination, since prallethrin has a rapid time to peak effect. 

At the next highest dose of 10 mg/kg/day, the incidence and frequency of trembling

substantially increased, with 5 dogs being affected on numerous occasions (over 40). 

Additionally, effects were seen much earlier (during 1 week). At 20 mg/kg/day, all dogs (8) 

were affected with increased frequency. At 10 and 20 mg/kg/day, the trembling was also 

accompanied by dose-related rapid eye blinking, hunched posture, salivation, and panting. 

Although the use of 5 mg/kg/day as a POD is a conservative approach, it is only 2 fold lower 

than where numerous clinical signs were observed (during week 1). The use of 5 mg/kg/day as 

the POD is supportable when all of the information is considered together (time to peak effect 

for prallethrin, dose response relationship at 5mg/kg/day, earlier onset of effects at 10 

mg/kg/day). Therefore, the chronic dog study was selected to protect for potential 

neurotoxicity. 

It is noteworthy to mention that the one dog in the 5 mg/kg/day group with clinical signs of 

neurotoxicity also had heart effects (red discoloration of the left ventricle and hemorrhage) that 

were not considered treatment-related as there was no dose response. Based on the available 

data, it is unclear whether the clinical signs observed in the dog are indicative of neurotoxicity 

or related to the heart effects also observed in the animal. It should be noted that the neurotoxic 

effects seen in the dog were also observed at higher doses in the absence of heart effects.

The developmental rat and rabbit, acute neurotoxicity, and WIL studies were all considered for 

risk assessment. Higher NOAELs were determined in the acute rat (ACN and WIL) and 

developmental rat and rabbit studies, so they were not selected for risk assessment. The WIL 

FOB study and the ACN study both used high vehicle volumes which likely impacted 

absorption characteristics of prallethrin thereby increasing the POD. Given what is known 

about pyrethroid toxicokinetics/dynamics, in general, and as there is no apparent increase in 

hazard from repeated/chronic exposures to prallethrin, the acute dietary exposure assessment is 

protective of chronic dietary exposures.

Incidental Oral Short-Term: For incidental oral exposure and assessment, the chronic dog 

study was also selected, based on neurotoxic effects observed beginning at week 4. Signs of 

neurotoxicity (trembling, convulsions, heavy panting, salivation, rapid eye blinking, and muscle 

twitching) were observed in one dog at the LOAEL of 5 mg/kg/day. Additionally, neurotoxicity 

was seen within hours of dosing prior to the death of the animal during week 44 (see acute 

dietary). The NOAEL of 2.5 mg/kg/day is protective of potential offspring/developmental 

effects, as well as systemic effects, including neurotoxicity, observed in the toxicology database

(see Section 5.4.3: Acute Dietary Risk Assessment).

Dermal Short-Term: For dermal exposure and risk assessment, the 21-day dermal toxicity 

study in rats was selected. The NOAEL is 30 mg/kg/day and the LOAEL is 150 mg/kg/day, 

based on clinical signs (fixation, abnormal gait, tremors, sensitivity to external stimuli, 

vocalization, twitching, and writhing spasms). The POD and endpoint are considered 

appropriate for short-term risk assessment because it is a route-specific study, the endpoint is 

based on the effect of concern (neurotoxicity), and there is no evidence of developmental toxicity 

or increased susceptibility. 
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Inhalation Short-Term: For inhalation exposure and risk assessment, the 28-day inhalation 

toxicity study in rats was selected. The NOAEL is 0.001 mg/L and the LOAEL is 0.0044 mg/L, 

based on nasal discharge, irregular respiration, decreased spontaneous activity, salivation, and 

incontinence. The dose and endpoint are appropriate because the effects were seen following 

exposure via the route (inhalation) and duration (short- and intermediate-term) of concern. 

Additionally, the endpoint is based on portal of entry effects (nasal discharge, irregular 

respiration), as well as the effect of concern (neurotoxicity), and there is no evidence of 

developmental toxicity or increased susceptibility. Human equivalent concentrations (HECs) for 

portal of entry and systemic effects were calculated for prallethrin. The portal of entry HECs 

were used for risk assessment and are considered protective of systemic effects since they were 

15x lower than the systemic HECs. 

The methods and dosimetry equations described in EPA’s reference concentration (RfC) 

guidance (1994) and OPP’s guidance on the application of the RfC methodology (2014) are 

suited for calculating HECs based on the inhalation toxicity NOAEL for use in MOE 

calculations. The regional-deposited-dose ratio (RDDR), which accounts for the particulate 

diameter (mass median aerodynamic diameter (MMAD) and geometric standard deviation (g) of 

aerosols), can be used to estimate the different dose fractions deposited along the respiratory 

tract. The RDDR is also based on interspecies differences in ventilation and respiratory-tract 

surface areas. Thus, the RDDR can be used to adjust an observed inhalation particulate exposure 

of an animal to the predicted inhalation exposure for a human (see toxicity endpoint summary 

table in Section 4.5.4 for values and Appendix A.4 for calculations).

.

HED’s Levels of Concern for Margin of Exposure

HED’s LOC for occupational and residential risks is based on the various uncertainty and safety 

factors retained or applied for specific routes of exposure. For inhalation risk assessments, the 

10x interspecies factor was reduced to 3x to account for interspecies differences, in accordance 

with the reference concentration (RfC) guidance. The intraspecies variability factor of 10x is 

combined with an interspecies extrapolation factor of 3x, based on the use of a human equivalent 

dose for inhalation risk assessment. Therefore, for inhalation risk assessments for adults and 

children 6 years of age or older, a 30x uncertainty factor has been retained. For children under 6 

years old, exposed via the inhalation route, the LOC is 100, based on a 10x factor for intraspecies 

variability, 3x for interspecies extrapolation, and 3x for juvenile sensitivity. For assessing 

dermal and oral exposures, the LOC for children under 6 years old is 300, based on the 

traditional 10x factors for intraspecies variability and interspecies extrapolation, and the 

additional 3x FQPA Safety Factor. For adults and children 6 years and older, the traditional 

factors apply (10x intraspecies and 10x interspecies) for dermal and oral exposures (Table 4.5.1).
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Table 4.5.1. HED’s LOCs for MOEs

Route LOC

Occupational Dermal Exposure 100x

Occupational Inhalation Exposure 30x

Residential Incidental Oral Exposure < 6 years old: 300x

Residential Dermal Exposure ≥ 6 years old: 100x

< 6 years old: 300x

Residential Inhalation Exposure ≥ 6 years old: 30x

< 6 years old: 100x

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

When there are potential occupational and residential exposures to a pesticide, the risk 

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

determine whether the individual exposures can be combined if they have the same toxicological 

effects. For prallethrin, dermal and oral exposures are both based on clinical signs related to 

neurotoxicity and should be combined for risk assessment. Although the LOAEL for inhalation 

is also based on neurotoxicity, derivation of the HECs used for inhalation risk assessment 

(Appendix A.4) show that assessing inhalation exposure based on the portal-of-entry effects is 

protective of the systemic endpoints (including neurotoxicity) since the portal of entry HEC is 

15x lower than the systemic HEC. As a result, inhalation exposure should not be combined with 

either the dermal or the oral routes of exposure. 

 

4.5.3 Cancer Classification and Risk Assessment Recommendation

Prallethrin is classified as “not likely to be carcinogenic to humans.” No tumors were observed 

in rat and mouse carcinogenicity studies up to the highest doses tested. For both the rat and 

mouse studies, the animals could have tolerated higher dose levels; however, HED determined 

that dose levels were adequate to assess potential carcinogenicity.

Prallethrin tested negative in the majority of the genotoxicity studies. It also tested negative in 

an in vitro chromosomal aberration study in Chinese Hamster Ovary (CHO K1) cells without 

metabolic activation, but tested positive at all doses with metabolic activation. However, 

clastogenicity was not clearly dose-related, was seen at nontoxic and slightly toxic doses, was 

not expressed in in vivo studies, and structure-activity comparisons with the other pyrethroids 

revealed no correlations with clastogenicity. Other gene mutation, chromosomal aberration, and 

unscheduled DNA synthesis (UDS) studies were negative. Therefore, there is no concern for 

genotoxicity.

4.5.4 Points of Departure and Toxicity Endpoints Used in Human Risk Assessment

Toxicity endpoints/PODs are given in the table below, and the full toxicological profile is 

presented in Appendix A.
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Table 4.5.4.a. Summary of Toxicological Doses and Endpoints for Prallethrin for Use in Dietary and 

Non-Occupational Human Health Risk Assessments

Exposure/ Scenario Point of Departure Uncertainty/FQPA 

Safety Factors

RfD, PAD, Level 

of Concern for 

Risk Assessment

Study and Toxicological 

Effects

Acute Dietary

(children ≥ 6 years old 

and adults) 

NOAEL = 2.5 

mg/kg/day

UFA= 10x

UFH=10x

FQPA SF= 1x

Acute RfD = 

0.025 mg/kg/day 

aPAD= 0.025 

mg/kg/day Chronic dog study 

(capsule)

LOAEL = 5 mg/kg/day 

based on clinical signs of 

neurotoxicity.

Acute Dietary 

(children<6 years old) 

UFA= 10x

UFH=10x

FQPA SF= 3x

Acute RfD = 

0.025mg/kg/day 

aPAD= 0.008 

mg/kg/day

Incidental Oral ShortTerm

(1-30 days)

UFA= 10x

UFH=10x

FQPA SF= 3x

Residential LOC 

for MOE = 300

Short-term Dermal

(1 to 30 days)

(children <6 years old) 

Dermal NOAEL= 

30 mg/kg/day

UFA= 10x

UFH =10x

FQPA SF= 3x

Residential LOC 

for MOE = 300

21-day Dermal Rat

LOAEL = 150 mg/kg/day 

based on observed clinical 

signs of toxicity (fixation, 

abnormal gait, tremors, 

sensitivity to external 

stimuli, vocalization, 

twitching and writhing 

spasms), all beginning 

between days 1 and 3 of a 

21 day dermal study in 

rats. 

Short-term Dermal

(1 to 30 days)

(children ≥ 6 years old 

and adults)

UFA= 10x

UFH =10x

FQPA SF = 1x

Residential LOC 

for MOE = 100

Short-term Inhalation

(1 to 30 days)

(children <6 years old) Inhalation NOAEL 

= 0.001 mg/L

HEC/HED 

calculations used for 

risk assessment (see 

below)

UFA= 3x

UFH =10x

FQPA SF= 3x

Residential LOC 

for MOE = 100

28-Day Inhalation Rat 

LOAEL = 0.0044 mg/L

based on irregular 

respiration, decreased 

spontaneous activity, 

salivation, incontinence, 

and nasal discharge.

Short-term Inhalation

(1 to 30 days)

(children ≥ 6 years old 

and adults) 

UFA= 3x

UFH =10x

FQPA SF= 1x

Residential LOC 

for MOE = 30
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Table 4.5.4.a. Continued. Summary of Toxicological Doses and Endpoints for Prallethrin for Use in 

Dietary and Non-Occupational Human Health Risk Assessments

Residential HECs and 

HEDs

Residential LOC for 

MOE = 100 (children 

<6 years old)

Residential LOC for 

MOE = 30

(children ≥ 6 years old 

and adults) 

Residential HECs HEDs

Handler/Outdoor

Postapplication

0.00020 mg/L 0.006 mg/kg/day

Indoor 

Postapplication

without air 

ventilation

0.00014 mg/L N/A*

Indoor 

Postapplication

with air ventilation

Adults: 0.00004 mg/L

Children: 0.00003 mg/L

N/A*

Bystander 0.00002 mg/L N/A*

Cancer (oral, dermal, 

inhalation)

Classification: “ Not Likely to be Carcinogenic to Humans.”

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

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = 

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

of concern. HEC = human equivalent concentration; HEC = POD x RDDR x daily duration x weekly duration. 

HED = human equivalent dose. HED = dose (systemic HEC value) mg/L x A (absorption) x CF (conversion factor) 

L/hr/kg) x D (duration-hours) x AF (activity factor). *MOEs calculated directly from HECs. 

Table 4.5.4.b. Summary of Toxicological Doses and Endpoints for Prallethrin for Use in 

Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertain

ty Factors

Level of Concern for 

Risk Assessment Study and Toxicological Effects

Short-term 

Dermal

(1 to 30 days)

Dermal 

NOAEL= 30 

mg/kg/day

UFA= 10x

UFH=10x Occupational LOC for 

MOE = 100

21-day Dermal Rat

LOAEL = 150 mg/kg/day based on 

observed clinical signs of toxicity 

(fixation, abnormal gait, tremors, 

sensitivity to external stimuli, 

vocalization, twitching and 

writhing spasms), all beginning 

between days 1 and 3 of a 21 day 

dermal study in rats
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Table 4.5.4.b. Summary of Toxicological Doses and Endpoints for Prallethrin for Use in 

Occupational Human Health Risk Assessments

Exposure/ 

Scenario

Point of 

Departure

Uncertain

ty Factors

Level of Concern for 

Risk Assessment Study and Toxicological Effects

Short-term 

Inhalation

(1 to 30 days)

Inhalation 

NOAEL = 0.001 

mg/L

HEC/HED 

calculations used 

for risk 

assessment (see 

below)

UFA= 3x

UFH=10x

Occupational LOC for 

MOE = 30

28-Day Inhalation Rat 

LOAEL = 0.0044 mg/L based on 

irregular respiration, decreased 

spontaneous activity, salivation, 

incontinence, and nasal discharge

Occupational 

HECs and 

HEDs

Occupational HECs HEDs

Ventilation rate=8.3 L/min

0.00010 mg/L

0.006 mg/kg/day

Ventilation rate=16.7 L/min 0.012 mg/kg/day

Ventilation rate=29 L/min 0.020 mg/kg/day

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not Likely to be Carcinogenic to Humans.”

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

used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human 

exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in 

sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of 

concern. HEC = human equivalent concentration; HEC = POD x RDDR x daily duration x weekly duration. HED 

= human equivalent dose. HED = dose (systemic HEC value) mg/L x A (absorption) x CF (conversion factor) 

L/hr/kg) x D (duration-hours) x AF (activity factor)

5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile

5.1.1 Summary of Plant and Animal Metabolism Studies

No metabolism studies in plants or animals have been conducted, and none are required, based 

on previous Agency discussions with the petitioner on 11/3/2010. For the use in food handling 

establishments and the proposed use over or near agricultural crops, EPA assumes that the 

residue of concern is the parent compound only.
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5.1.2 Summary of Environmental Degradation

Prallethrin has a relatively low solubility in water, and adheres moderately to soil containing 

organic material (organic sorption KOC = 2,533 mL/g). The potential for prallethrin to move off 

the site of application with rain or irrigation water (mobility) is moderate. Prallethrin degrades 

rapidly via photolysis (sunlight) when it is in the air, but more slowly when it is in/on vegetation, 

soil, or water. Prallethrin is moderately persistent. It is likely to take between 1 week and 2 

months (t1/2 = 3 to 37 days) for prallethrin to degrade to half of the applied concentration (in/on 

soil, water, or vegetation). 

5.1.3 Comparison of Metabolic Pathways

As metabolism studies were not performed on plant or livestock commodities, comparison of the 

relevant metabolic pathways is not possible. For a discussion of metabolism in rats, see Section 

4.2.

5.1.4 Residues of Concern Summary and Rationale

For the use in food handling establishments and the proposed use over or near agricultural crops, 

EPA assumes that the residue of concern is the parent compound only. Given that residues 

resulting from the mosquitocide use are expected to be very low or non-detectable, there are no 

residues expected in rotational crops.

Table 5.1.4. Summary of Metabolites and Degradates to be included in Risk Assessment and 

Tolerance Expression

Matrix Residues Included in Risk 

Assessment

Residues Included in Tolerance 

Expression for Compliance Monitoring

Plants Primary Crops Prallethrin Prallethrin

Rotational Crops Not Applicable Not Applicable

Livestock Ruminants Prallethrin Prallethrin

Poultry Prallethrin Prallethrin

Drinking Water Prallethrin Not Applicable

5.2 Food Residue Profile

In support of the proposed adulticide use, the registrant submitted residue trials for prallethrin on 

alfalfa, grass, and leaf lettuce. Three trials (1 for each crop) were conducted in the US in typical 

growing areas for these crops and in accordance with study protocols agreed to in discussions 

with the Agency. The protocol specified that applications would be made at the 1x and 10x 

application rates from an elevation of 50 feet above ground. The prallethrin residue data are 

summarized in Table 5.2.1.
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In the residue trials, applications were made in the airspace above leaf lettuce, alfalfa, and Sudan 

grass at a 10x label application rate (0.0072 lb a.i./Acre). In addition, a trial was performed on

alfalfa at a 1x application rate (0.00072 lb a.i./Acre). Thirty-six samples were analyzed from 

each trial. None of the samples of alfalfa treated at the 1x application rate or leaf lettuce treated 

at the 10x application rate contained residues above the LOQ of 0.01 ppm. Only one sample of 

alfalfa treated at the 10x application rate contained quantifiable residues (0.0107 ppm). 

However, 11 of the 36 samples of Sudan grass forage contained quantifiable residues. The 

highest residue was 0.045 ppm.

The submitted alfalfa, grass, and leaf lettuce field trial data are adequate, and demonstrate that 

the use of the mosquitocide in accordance with the registered label would result in very low 

residues, in the range of the LOQ. The existing established tolerance for prallethrin residues of 

1.0 ppm in/on all food commodities, resulting from use of the insecticide in FHEs, is adequate to 

cover residues resulting from the proposed use in the vicinity of, or the airspace above, 

agricultural field crops. 

 

Table 5.2.1. Summary of Residue Data from Crop Field Trials with Prallethrin

Crop n Use

Rate1

Number 

of NDs2

Number of 

Peaks at RT3

Number 

<LOD4

Number >LOD 

and <LOQ5

Number 

>LOQ

Highest 

Residue (ppm)

Leaf Lettuce 36 10x 31 5 2 3 0 0.00994

Alfalfa 36 1x 36 0 0 0 0 0

Alfalfa 36 10x 24 12 3 7 1 0.0107

Sudan Grass 36 10x 5 31 4 16 11 0.0450

1. 1x use rate = 0.00072 lb ai/A, 10x use rate = 0.0072 lb ai/A. 

2. ND = Not Detected. No visible peak was seen in the chromatogram at the retention time (RT) of prallethrin. 

3. In these samples, there was a visible peak present at the RT of prallethrin; some were below the LOD. 

4. LOD = 0.003 ppm. 

5. LOQ = 0.010 ppm. 

There are no Codex or Canadian MRLs for prallethrin. As a result, there are no harmonization 

issues for the chemical with respect to either the residue definition or to MRLs.

The registrant has not submitted processing studies or livestock feeding studies for prallethrin, 

and none are needed.

As agricultural crops are not being directly treated, and water concentrations are expected to be 

extremely low, bioconcentration in fish is not an issue for prallethrin.

5.3 Water Residue Profile

EFED provided the results of a drinking water assessment that was performed for prallethrin 

(D408885, H. Zhong, 2/4/2013). In this memo, EFED stated that the results of a previous 

assessment (D274758, J. Melendez, 6/30/2003) should be used in the current dietary exposure 

and risk assessment. In the 2003 assessment, the acute (peak) and annual average surface water

concentrations were generated using the FIRST Model, and the groundwater concentrations were 

generated using the SCIGROW Model. The estimated drinking water concentration (EDWC) for 

the acute assessment was 0.591 ppb and that for the chronic assessment was 0.0375 ppb. The 
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groundwater value was 0.001 μg/L. The surface water EDWCs of 0.591 ppb and 0.0375 ppb

were used instead of the groundwater value because they were higher and, therefore, more 

conservative. The drinking water models EFED uses and their descriptions are available at the 

EPA internet site: http://www.epa.gov/oppefed1/models/water/. 

5.4 Dietary Risk Assessment

Acute and chronic aggregate dietary (food and drinking water) exposure and risk assessments 

were conducted using the Dietary Exposure Evaluation Model software with the Food 

Commodity Intake Database (DEEM-FCID) Version 3.16. This software uses 2003-2008 food 

consumption data from the U.S. Department of Agriculture’s (USDA’s) National Health and 

Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). The chronic 

assessment was conducted solely for the purpose of obtaining estimates of background levels of 

dietary exposure for estimating aggregate risk.

5.4.1 Description of Residue Data Used in Dietary Assessment

Acute Assessment

The acute assessment is partially refined. It is based on the assumption that most commodities 

will have residues at one-half the LOQ of the analytical method used in the FHE residue trials 

(0.05 ppm). It was also based on the assumptions that all flour food forms will contain residues 

at the highest level found in the FHE residue trials on flour, and that tree nuts and peanuts will 

contain residues at the highest level found in the FHE residue trials on peanuts. The 4.65% of 

FHE facilities treated estimate from BEAD was used to calculate the number of zeros used in the 

RDFs for nonblended and partially blended commodities. The zeros were replaced with the 

highest residue from the mosquito adulticide trials (0.0045 ppm). In addition, 0.0045 ppm was 

added to the residue values in the RDFs. For blended commodities, the residue value was 

multiplied directly by the percent FHE value (0.0465) and 0.0045 ppm was added. By treating 

the data in this manner, the percent FHE value was applied to the FHE residue values, and the 

adulticide residues were incorporated at a level of 100%. A modeled EDWC of 0.000591 ppm

from EFED was used for drinking water, as discussed in the Water Residue Profile section above 

(Section 5.3). Processing factors were not used because the assumption was made that foods in 

an FHE could be treated after processing.

Chronic Assessment

The chronic dietary exposure assessment is partially refined. The exposure estimates are based 

on the highest residue value from the FHE residue trials for tree nuts, peanuts, and all flour food 

forms; and on the LOQ of the method used in the FHE trials (0.10 ppm). The data were treated 

in the same manner as the data for the blended commodities in the acute assessment, with the 

exception that the average residue value from the adulticide trials (0.0007 ppm) was used instead 

of the highest residue value (0.0045 ppm). As a result, the residue value was multiplied by 

0.0465 and 0.0007 ppm was added. As with the acute assessment, by treating the data in this 

manner, the percent FHE value was applied to the FHE residue values, and the adulticide 

residues were incorporated at a level of 100%. Finally, a modeled EDWC of 0.0000375 ppm
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from EFED was used for drinking water, as discussed in the Water Residue Profile section above 

(Section 5.3). Processing factors were not used because the assumption was made that foods in 

an FHE could be treated after processing.

 

Cancer Assessment

Cancer risk is not of concern for prallethrin because the compound is classified as “not likely to 

be carcinogenic to humans.” 

5.4.2 Percent Crop Treated Used in Dietary Assessment

BEAD provided an estimate of a 4.65% probability that a food a person consumes contains 

residues as a result of treatment in an FHE at some point with any pesticide (i.e., it is not specific 

to prallethrin). For both the acute and chronic assessments, this value was used for all 

commodities with the exception of drinking water. With respect to the mosquito adulticide 

application, the assumption was made that 100% of all commodities would contain residues as a 

result of this use. 

5.4.3 Acute Dietary Risk Assessment

The acute risk estimates are below HED’s LOC for all population subgroups, including those 

comprised of infants and children. Generally, HED is concerned when risk estimates exceed 

100% of the population-adjusted dose (PAD). The acute risk estimate for the general U.S. 

population is 10% of the aPAD. The population subgroup with the highest acute dietary risk 

estimate is Children 1-2, which uses 76% of the aPAD. As a %FHE treated estimate was used 

for all commodities, the risk estimates are being reported at the 99.9th percentile of exposure. 

The acute dietary exposure and risk estimates are given in Table 5.4.5.

As stated above, the acute assessment is partially refined; however, there is still a significant 

degree of conservatism in the assessment. The residue levels are from trials designed to produce 

maximum residues. Typically, residues in foods at the time of consumption are lower than those 

obtained from such trials. 

The percent FHE treatment estimate provided by BEAD is a conservative estimate of FHE 

treatment with prallethrin. It represents the probability that a food a person consumes contains 

residues as a result of treatment in an FHE at some point with any pesticide, and is not specific to 

prallethrin. Sales and production data for prallethrin indicate that the percent of facilities treated 

with that chemical are lower than the all-pesticide estimate. In addition, the conservative 

assumption was made for the mosquito adulticide use that all commodities would be treated to a 

level of 100%, (i.e., all crops contain inadvertent residues resulting from mosquito control use),

and residues would be present at the maximum level found in the adulticide trials.
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5.4.4 Chronic Dietary Exposure Assessment

The chronic dietary exposure estimates range from 0.000102 to 0.000581 mg/kg/day. The 

chronic assessment is partially refined. As with the acute assessment, the inputs to the chronic 

assessment convey significant conservatism in both the residue values used and the application 

of the percent-of-treatment estimates. The chronic dietary exposure estimates are given in Table 

5.4.5.

5.4.5 Summary Table

Table 5.4.5. Summary of the Acute Exposure and Risk Estimates for Prallethrin

Population Subgroup

Acute Assessment (99.9th Percentile) Chronic Assessment

aPAD, 

mg/kg/day

Exposure Estimate, 

mg/kg/day

% aPAD cPAD,

mg/kg/day

Exposure Estimate, 

mg/kg/day

% 

cPAD

U.S. Population 0.025 0.002536 10 NA 0.000155

NA

All infants 0.0083 0.004464 54 NA 0.000263

Children 1-2 yrs* 0.0083 0.006275 76 NA 0.000581

Children 3-5 yrs 0.0083 0.003609 43 NA 0.000421

Children 6-12 yrs 0.025 0.002335 9.3 NA 0.000253

Youth 13-19 yrs 0.025 0.001343 5.4 NA 0.000137

Adults 20-49 yrs 0.025 0.000959 3.8 NA 0.000116

Adults 50-99 yrs 0.025 0.000855 3.4 NA 0.000102

Females 13-49 yrs 0.025 0.000998 4.0 NA 0.000110

*Most highly exposed population subgroup

6.0 Residential Exposure and Risk Estimates

(M. Collantes, D407642, 8/9/2013 and D417631, 5/8/2014)

There are no new proposed residential uses at this time; however, there are existing residential 

uses as well as products registered for controlling public health pests (mosquito control) in 

outdoor residential and recreational areas and in vegetation surrounding parks, woodlands, 

swamps, marshes, overgrown areas, and golf courses. Several of these registered residential uses 

were evaluated in the 1999 occupational and residential exposure (ORE) assessment and have 

since been cancelled or removed from the label. The remaining registered residential use 

scenarios have been reassessed in this document to reflect updates to HED’s 2012 Residential 

SOPs, along with policy changes for body weight assumptions and updated inhalation 

toxicological endpoints and points of departure.

The toxicological profile of pyrethroids characterizes pyrethroids, including prallethrin, as being 

rapid in onset and associated with acute, peak exposures. Although the single day, acute studies 

for prallethrin do not provide the most sensitive PODs, neurotoxicity was observed in most of the

repeat-dose toxicology studies within a few days of dosing. As such, the totality of the 

information suggests that only single day risk assessments need to be conducted for prallethrin. 

Based on the toxicity profile, HED did not conduct an intermediate or long-term exposure 

assessment for adults or children. A short-term exposure assessment is protective of exposures 

with longer durations.
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6.1 Residential Handler Exposure/Risk Estimates

The prallethrin labels do not identify the residential use products as restricted use; therefore, a 

revised residential handler exposure assessment was performed to be protective of potential 

homeowners who apply prallethrin products. The quantitative exposure/risk assessment 

developed for residential handlers is based on the following scenarios: 

 Applying a fogger to indoor use sites, and

 Mixing/Loading/Applying spray to lawns

Combining Exposures/Risk Estimates:

Residential exposure pathways for adults include dermal and inhalation routes for applicationrelated scenarios. For prallethrin, dermal and inhalation exposures are both based on clinical 

signs related to neurotoxicity. However, the HEC for inhalation exposure was based on portal of 

entry effects that resulted in lower HECs than the HEC for systemic (neurotoxicity) 

effects. Therefore, the portal of entry HEC is protective of the neurotoxic systemic effects, and 

inhalation and dermal routes of exposure should not be combined.

Summary of Residential Handler Exposure and Risk Estimates

Registered residential uses were reassessed using the revised 2012 Residential SOPs and a new 

inhalation endpoint and point of departure. All residential handler scenarios resulted in dermal 

and inhalation risk estimates greater than their respective LOCs (dermal MOE ≥ 100 and 

inhalation MOE ≥ 30) and are not of concern. A quantitative assessment was not required for 

handling of the total release fogger product since the labels state that room/house must be 

vacated immediately by the user once fogger is initiated. The residential handler exposure risk 

estimates are summarized in Table 6.1. 
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 Table 6.1. Registered Residential Handler Exposure and Risk Estimates for Prallethrin 

Exposure Scenario Level of 

Concern

Dermal Unit 

Exposure 

(mg/lb ai)

Inhalation Unit 

Exposure

(mg/lb ai)

Maximum 

Application 

Rate1

Area Treated 

Daily2

Dermal Inhalation

Dose

(mg/kg/day)3 MOE4 Dose (mg/kg/day)5 MOE6

MGK Formula 2964 

Microencapsulated Suspension 

Concentrate Insecticide

(1.6% a.i.)

Reg. No. 1021-2574

Dermal 

LOC = 100

Inhalation 

LOC = 30

13.4

hose-end 

sprayer

0.022

hose-end 

sprayer

0.045 lb ai/A 0.5 A 0.0038 8000 0.0000062 970

130

backpack

0.14 backpack 0.00011

lb ai/ gal 1,200 ft2 0.0021 14,000 0.0000023 2,600

EVERCIDE® NYlAR Total 

Release Aerosol Fogger 2644

Reg. No. 1021-1656

Quantitative assessment not required because the labels state that room/house must be vacated immediately once 

fogger is initiated. Do not remain in area during treatment.

1 Based on registered labels. 

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

3 Dermal Dose = Dermal Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated × Dermal Absorption Factor (%) ÷ Body Weight (80 

kg).

4 Dermal MOE = Dermal NOAEL (30 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

5 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or gal) × Area Treated (A/day or gallons/day) ÷ Body Weight (80 kg).

6 Inhalation MOE = Inhalation HED (0.006 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
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6.2 Post-Application Exposure

There is the potential for residential post-application exposure for individuals exposed as a result 

of being in an environment that has been previously treated with prallethrin. A residential postapplication exposure assessment was previously performed for the mosquito control (G. Bangs, 

D293820, 9/30/2003) as well as for indoor and pet uses (M. Collantes, D260355, 11/17/1999). 

Several of the previously assessed residential products have been cancelled or removed from 

current labels. Risk estimates for the mosquito control and remaining registered residential postapplication exposure scenarios are revised in this assessment to incorporate the use of new 

toxicological inhalation endpoints and points of departure, the revised 2012 Residential SOPs 

and appropriate body weights and life stages. The quantitative exposure/risk assessment for 

residential post-application exposures is based on the following short-term duration scenarios: 

 Dermal exposure from contact with residues deposited on turf resulting from mosquito 

control;

 Incidental oral (hand-to-mouth) contact with residues deposited on turf resulting from 

mosquito control;

 Inhalation exposure of residues resulting from mosquito vector control;

 Dermal exposure from contact with residues deposited on indoor surfaces from fogger;

 Incidental oral (hand-to-mouth) contact with residues deposited on indoor surfaces from 

fogger;

 Inhalation exposure of residues resulting from exposure to indoor pesticide vapors from 

fogger;

 Dermal exposure from contact with residues deposited on turf/lawns; and

 Incidental oral (hand-to-mouth) contact with residues deposited on turf/lawns

Combining Exposures and Risk Estimates:

The child dermal and incidental oral routes of exposure are generally combined as it is likely that 

they can occur simultaneously based on the use pattern, and the toxicological effects across these 

routes of exposure are the same. Therefore, exposure from the incidental oral route should be 

combined with dermal exposure and background exposure from food and water in order to 

complete an undated aggregate risk assessment for prallethrin.

Mosquito Adulticide Use

No chemical-specific exposure data have been submitted to support the mosquito adulticide use. 

Therefore, 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, and determines the amount of application volume that remained aloft and 

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

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

concentrations in the breathing zones of adults and children for use in calculating the postapplication inhalation risks to individuals residing in areas being treated by aerial application of 

prallethrin. Post-application inhalation estimates resulting from aerial applications have been 
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revised to incorporate the new HEC which is based on a 4-hour exposure duration. Furthermore, 

to calculate refined airborne concentrations from ULV truck fogger applications, HED used the 

2012 Residential SOPs for Outdoor Fogging/Misting Systems, with minimal modification to the 

Well-Mixed Box (WMB) Model. For both adults and children, the exposure duration was 

adjusted to 4 hours as opposed to a default of 1.5 hours to mimic an exposure duration consistent 

with the 4-hour animal inhalation toxicity study used to define the endpoint and POD used as the 

basis of this assessment. The WMB Model allows for the estimation of air concentrations in the 

breathing zones of adults and children for use in calculating the post-application inhalation 

exposure to individuals residing in areas being treated by ground application of prallethrin. This 

methodology is a modification of the previous method used in assessing post-application 

inhalation exposure resulting from truck mounted mosquito fogger. The revised methodology 

more accurately accounts for dilution using the WMB Model as discussed above. 

All post-application mosquito control exposure scenarios resulted in MOEs greater than their 

respective LOCs and are not of concern. Table 6.2.1 provides a summary of the calculated air 

concentrations and respective inhalation MOEs resulting from aerial and ground (fogger truck) 

applications of prallethrin. 

Table 6.2.1. Inhalation Exposure & Risk Estimates from Mosquito Adulticide Using the 

AgDISP and WMB Models.

Population Air Concentration 

Estimate (mg/m3)

HECd (mg/m3) Inhalation MOEe

Aerial ULV (100 ft release height) – AGDISP Model

Adults 0.00014a

0.2 1400

Children 1 to <2 

years old 0.00015b 1300

ULV Truck Fogger – WMB Model

Adults 0.000014c 0.2 1400

Children 1 to <2 

years old

a Air concentration estimate produced from AGDISP Model at approximately 6 feet from ground.

b Air concentration estimate produced from AGDISP Model at approximately 3 feet from ground.

c Air concentration estimate produced from WMB Model

d Human equivalent concentration (HEC) = 0.2 mg/m3

e Inhalation MOE = HEC (0.2mg/m3) /Air Concentration (mg/m3)

The AGDISP Model is also capable of estimating the amount of residues depositing on turf for 

use in calculating the dermal post-application risk estimates to individuals residing in areas being 

treated by aerial application of prallethrin. For ground-based ULV applications, a 5% deposition 

is used based on a study conducted by Teitze et al., (Mass Recovery of Malathion in Simulated 

Open Field Mosquito Adulticide Tests; Archives of Environmental Contamination and 

Toxicology; 26: 473-477; 1994). The 2012 Lawn and Turf Residential SOP for dermal postapplication exposure was used to estimate resulting TTRs for dermal and incidental oral (handto-mouth) exposure estimates resulting from aerial and ground applications. The TTRs were 
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adjusted for air (0.79) deposition provided by AGDISP and ground (0.05) deposition provided by 

data in the Teitze et al., study. The hand-to-mouth scenario represents the worst case incidental 

oral exposure scenario and is thus protective of all other incidental oral scenarios. Tables 6.2.2 

and 6.2.3 provide a summary of the post-application dermal and incidental oral exposure 

estimates. Table 6.2.4 provides a summary of the combined dermal and incidental oral risk 

estimates.

Table 6.2.2. Dermal Post-application Exposure Estimates Resulting from Multicide 2798 Reg. 

No. 1021-1795 and Multicide 2922 Reg. No. 1021-2562.

Use Application 

Rate

(lb ai/A)

TTRa

(ug/cm2)

AGDISP 

Deposition 

Fraction

Adjusted 

TTRb

(ug/cm2)

Transfer 

Coefficientc

(cm2/hr)

Dermal Dosed 

(mg/kg/day)

Dermal 

MOEe

Adult

air

0.00072 0.0008

0.79 0.000063 180,000 0.0002 140,000

ground 0.05 0.000004 49,000 0.00001 2,200,000

Child (1-2 yrs)

air

0.00072 0.0008

0.79 0.000063 180,000 0.0004 71,000

ground 0.05 0.000004 49,000 0.00003 1,100,000

a. TTRt = AR (0.00072 lb ai/A) * F (0.01) * (1-FD)

t * CF2(4.54 x 108 μg/lb) * CF3(2.47 x 10-8 A/cm2

).

b. Adjusted TTR(ug/cm2) = TTR (0.0008 ug/cm2) x AgDISP Deposition Fraction (0.79 aerial or 0.05 dermal)

c. Transfer Coefficient (cm2/hr) = See Turf SOP In Appendix B in D407643 or Appendix A in D417631

d. Dermal Dose (mg/kg/day) = TTRt * CF1 (0.001 mg/μg) * TC * ET (1.5 hrs)

e. Dermal MOE = NOAEL (30 mg/kg/day)/Dermal Dose (mg/kg/day) ; Adult LOC = MOE ≥ 100; Child (1-2 yrs) LOC = 

MOE ≥ 300

Table 6.2.3. Incidental Oral Exposure Estimates Resulting from Multicide 2798 Reg. No. 1021-

1795 and Multicide 2922 Reg. No. 1021-2562.

Use Application Rate

(lb ai/A)

Hand Residuea

(mg/cm2)

Incidental Oral Dose b 

(mg/kg/day) Incidental Oral MOEc

air

0.00072

0.0000008 0.00001 290,000

ground 0.0000001 0.000001 4,600,000

a. Hand Residue = 

SA * 2

Fai *DE

HR

H

hands



b. Incidental Oral Dose (mg/kg/day) = [HR * (FM * SAH) * (ET * N_Replen) * (1- (1- SE)

(Freq_HtM/N-Replen))]

c. Incidental Oral MOE = NOAEL (2.5 mg/kg/day)/Incidental Oral Dose (mg/kg/day) ; LOC = MOE ≥ 300

Table 6.2.4. Combined Dermal and Incidental Oral Post-application Exposure and Risk Estimates

Lifestage Use Site Route of 

Exposure

Application 

Rate1

Air 

Concentration 

Estimate (mg/m3)

Dose 

(mg/kg/day)2

or (mg/m3) 

MOEs4 Combined 

MOE

Adult Truck Mounted Fogger

Multicide 2798 

Reg. No 1021-1795

(0.075 lb ai/gal)

and

Dermal

0.00024 -

0.00072

NA 0.0001 2,200,000

Inhalation 0.00014 NA 1,400 NA

Child

Dermal

NA

0.00003 1,100,000

Hand to Mouth 0.000001 4,600,000 900,000

Inhalation NA 1,400
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Table 6.2.4. Combined Dermal and Incidental Oral Post-application Exposure and Risk Estimates

Lifestage Use Site Route of 

Exposure

Application 

Rate1

Air 

Concentration 

Estimate (mg/m3)

Dose 

(mg/kg/day)2

or (mg/m3) 

MOEs4 Combined 

MOE

Multicide 2922

Reg. No. 1021-2562 

(0.084 lb ai/gal)

lb ai/acre

(0.41 – 1.23

fl oz/acre)

0.00014 NA

Adult

Aerial Application

Multicide 2798 

Reg. No 1021-1795

(0.075 lb ai/gal)

and

Multicide 2922

Reg. No. 1021-2562 

(0.084 lb ai/gal)

Dermal NA 0.0002 140,000

Inhalation 0.00014 NA 1,400 NA

Dermal NA 0.0004 71,000

Hand to Mouth NA 0.00001 290,000 57,000

Inhalation 0.00015 NA 1,300 NA

1 Based on registered or proposed labels.

2 Dose (mg/kg/day)(see equations in Appendix A and B of D417631 ORE assessment)

3 MOE = POD (mg/kg/day or mg/m3) ÷ Dose or air concentration (mg/kg/day or mg/m3).

4. Combined MOE = 1 ÷[(1 ÷ Dermal MOE) + (1 ÷ Inhalation MOE)].

Registered Residential Uses

For the purpose of conducting an aggregate (dietary and residential exposure) a revised 

residential post-application exposure assessment was also performed for turf and indoor fogger 

uses. All post-application residential exposure scenarios resulted in MOEs greater than their 

respective LOCs and are not of concern. Furthermore, all combined post-application exposure 

scenarios (i.e., child dermal + hand-to mouth) resulted in MOEs greater than their respective 

LOCs and are not of concern. Table 6.2.5 provides a summary of the residential post-application 

exposure risk estimates.

Table 6.2.5. Residential Post-application Exposure and Risk Estimates

Lifestage Use Site Route of 

Exposure

Application 

Rate1

Air 

Concentration 

Estimate (mg/m3)

Dose 

(mg/kg/day)2

or (mg/m3) 

MOEs4 Combined 

MOE

Adult MGK Formula 2964 

Microencapsulated 

Suspension Concentrate 

Insecticide for use on 

Lawns

(1.6% a.i.)

Reg. No. 1021-2574

Dermal

0.045 lb ai/A 

or 

0.00011 lb ai/ 

gal

NA

0.017 1,800

Inhalation NA NA

Child

Dermal 0.033 900

Hand to Mouth 0.0007 3,600 730

Inhalation NA NA

Adult EVERCIDE NYLAR 

Total Release Aerosol 

Fogger (Indoor Use)

Reg. No. 1021-1656

Dermal

1 fogger can 

deposited 

residues – 0.1 

ug/cm2

NA

0.0041 7,400

Inhalation NA NA

Child

Dermal 0.0039 7,600

Hand to Mouth 0.00058 4,200 2,700

Inhalation NA NA

1 Based on registered or proposed labels.

2 Dose (mg/kg/day)(see equations in Appendix A and B of D417631 ORE assessment)

3 MOE = POD (mg/kg/day or mg/m3) ÷ Dose or air concentration (mg/kg/day or mg/m3).

4. Combined MOE = 1 ÷[(1 ÷ Dermal MOE) + (1 ÷ Inhalation MOE)].
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Since the estimated residential turf post-application exposure for residential turf/mower/golf 

course using default TTR values for prallethrin is not minimal in comparison to the level of 

concern (i.e., the calculated MOE is not greater than 10 times higher than the level of concern, 

MOE = 900 compared to the LOC of 3000), future refinements of this post-application exposure 

for prallethrin may be necessary due to increased use of prallethrin or advances in EPA risk 

assessments. Therefore, EPA is requiring the 40CFR TTR data requirement to facilitate any 

necessary exposure assessment refinement and to further EPA’s general understanding of the 

availability of turf transferable pesticide residues.

6.3 Residential Risk Estimates for Use in Aggregate Assessment

For the purpose of performing an aggregate assessment, HED selected only the most 

conservative, or worst case, residential adult scenario to be included in the aggregated estimates, 

based on the lowest overall MOE (i.e., highest risk estimates). Although post-application 

inhalation exposure from mosquito adulticide applications via aerial application for adults and 

children resulted in the most conservative exposure risk estimates, the inhalation POD was based 

on portal of entry effects. For the purpose of performing an aggregate assessment, exposure 

based on portal of entry effects should not be combined with exposure from background dietary 

(food and water) exposure. Therefore, worst case post-application dermal and incidental oral 

(children only) exposures resulting from use of prallethrin on turf were used to estimate 

aggregate exposure (i.e., these exposure estimates were added to background exposure from food 

and water, Section 7). All scenarios resulted in MOEs greater than their respective LOCs and are 

not of concern. The dermal risk estimates resulted in an MOE of 1,800 for adults and 900 for 

children. The incidental oral risk estimate for children resulted in an MOE of 3,600. Combined 

dermal and incidental oral risk estimates resulted in MOEs equal to or greater than 730. A 

summary of the residential exposures and risk estimates recommended for the aggregate 

assessment is provided in Table 6.3.
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Table 6.3. Residential Risk Estimates for Use in Aggregate Assessment

Residential Handler Residential Post-application

Scenario

Dose (mg/kg/day)2 MOE3

Dose (mg/kg/day)4 or 

Air Concentration (mg/m3) 

MOEs5 Combined 

MOE

Dermal Inhalation Total Dermal Inhalation Total Dermal Inhalation Oral Total Dermal Inhalation Oral

Adult Turf 0.0038 0.0000062 NA 8,000 970 NA 0.017 NA NA NA 1,800 NA NA NA

Child Turf NA 0.033 NA 0.0007 900 3,600 730

1 Shaded 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 6.1. 

3 Residential Handler MOE = the MOEs associated with the highest doses identified in Table 6.1.

4 Residential Post-application Dose = the highest dose for each applicable lifestage of all scenarios assessed from Table 6.2.5.

5 Residential Post-application MOE = the MOEs associated with the highest doses identified in Table 6.2.5
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6.4 Residential Bystander Post-application Inhalation Exposure

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

assessment is not being performed for prallethrin at this time primarily because of the low 

proposed use rate (0.00072 lb ai/A). However, volatilization of pesticides can be a source of 

post-application inhalation exposure to individuals in close proximity to 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. The Agency is in the 

process of evaluating the SAP report and might, 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 might revisit the need for a quantitative post-application inhalation exposure assessment 

for prallethrin.

6.5 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom, airblast; 

and truck mounted ULV fogger for mosquito adulticide vector control) employed for prallethrin. 

The Agency has been working with the Spray Drift Task Force (a task force composed of various 

registrants which was developed as a result of a Data Call-In issued by EPA), 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). 

The Agency is also taking means to qualitatively and quantitatively address spray drift as a 

potential source of exposure in risk assessments for pesticides through existing programs such as 

Ag Drift and chemical specific properties of pesticides. The potential for spray drift will be 

quantitatively evaluated for each pesticide during the Registration Review process which ensures 

that all uses for that pesticide will be considered concurrently.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risk estimates 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 risk estimates themselves can 

be aggregated. When aggregating exposures and risks from various sources, HED considers 

both the route and duration of exposure.

7.1 Acute Aggregate Risk

Acute aggregate risk of exposure to prallethrin results from exposure to residues in food and 

drinking water alone. The acute dietary exposure analysis included both food and drinking 

water; therefore, acute aggregate risk estimates are equivalent to the acute dietary risk estimates,
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as discussed in Section 5.4.3, above. Acute aggregate risk is not of concern for the general U.S. 

population or any population subgroup.

7.2 Short-Term Aggregate Risk Estimates

Short-term aggregate risk assessments are needed for adults and children, and include exposure 

through the oral and dermal routes. The oral endpoint is based on neurotoxic effects seen in the 

chronic dog study in which the NOAEL was 2.5 mg/kg/day. The dermal endpoint is based on 

neurotoxic effects seen in the 21-day rat dermal study in which the NOAEL was 30 mg/kg/day. 

As the dietary, dermal, and incidental oral PODs are all based on neurotoxic effects, the 

exposures from these pathways are aggregated. For adults, post-application dermal exposure 

estimates resulting from use on turf were combined with background exposure from food and 

water. For children, post-application incidental oral (i.e., hand to mouth) exposures were 

combined with background exposure from food and water and then aggregated with dermal 

exposure. 

As indicated previously, the HECs used for inhalation risk assessment were based on portal of 

entry effects, and should not be combined with dermal or oral exposures, which result in 

systemic effects.

The chronic dietary exposure estimates are the background exposure levels that were added 

directly to the residential dermal and incidental oral post-application exposure estimates. Of the 

population subgroups that include adults, the U.S. population had the highest dietary exposure 

estimate. Risk to adult females was assessed by determining risk to Females 13-49 years old. 

For the population subgroups comprised of children, the most highly exposed subgroup was

Children 1-2 years old.

As the levels of concern are identical, the 1/MOE approach is used for calculating the short-term 

aggregate MOEs. The short-term aggregate risk assessments resulted in an MOE of 620 for 

children and an MOE of 1,600 for adult females and the general U.S. population. The adult and 

child MOEs are greater than their respective LOCs of 100 and 300. As a result, the short-term 

aggregate risk estimates are not of concern for the general U.S. population or any population 

subgroup. The short-term aggregate risk estimates are given in Table 7.2 and the equations used 

to determine the aggregate MOEs are given in Appendix D.
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Table 7.2. Short-Term Aggregate Risk Calculations

1/MOE Approach – All Levels of Concern are Identical

Population

Short-Term Scenario

LOC for 

Aggregate 

Risk1

Dietary

MOE

MOE Oral 

Residential 

Exposure

MOE Dermal 

Residential 

Exposure2

MOE 

Inhalation 

Residential 

Exposure

Aggregate 

MOE (food, 

water, and 

residential)

U.S. Population 100 16,129 NA 1,777 NA 1,600

Females 13-49 100 22,727 NA 1,777 NA 1,600

Children 1-2 300 4,303 3,648 898 NA 620

1. An UF of 100x was applied to adults to account for interspecies extrapolation (10x) and intraspecies variation 

(10x). No additional uncertainty factors/safety factors are required for adults.

An FQPA Safety Factor of 3x was applied to children <6 years of age

2. Residential Exposure = Dermal exposure from treated turf (see table 6.3). 

8.0 Cumulative Exposure/Risk Characterization

The Agency is required to consider the cumulative risks of chemicals sharing a common 

mechanism of toxicity. The Agency has determined that the pyrethroids and pyrethrins share a 

common mechanism of toxicity (http://www.regulations.gov; EPA-HQ-OPP-2008-0489-0006). 

The members of this group share the ability to interact with voltage-gated sodium channels 

ultimately leading to neurotoxicity. The cumulative risk assessment for the pyrethroids/ 

pyrethrins was published on 11/9/2011 and is available at http://www.regulations.gov; EPA-HQOPP-2011-0746. No cumulative risks of concern were identified, allowing the Agency to 

consider new uses for pyrethroids. For information regarding EPA’s efforts to evaluate the risk 

of exposure to this class of chemicals, refer to 

http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html.

Prallethrin is included in the pyrethroids/pyrethrins cumulative risk assessment. No dietary, 

residential, or aggregate risk estimates of concern have been identified in the single chemical 

assessment. In the cumulative assessment, residential exposure was the greatest contributor to 

the total exposure. An existing residential turf use for prallethrin was evaluated to determine the 

potential contribution it would have on the cumulative risk assessment. Although the turf use 

was considered the main contributor for residential exposure, the turf assessment indicated that 

exposure from turf would not impact the residential component of the cumulative risk estimate 

for pyrethroids. Therefore, as the proposed mosquito adulticide use contributes far less exposure 

than the registered turf uses, there will be no impact on the residential component of the 

cumulative risk estimates.

Dietary exposures make a minor contribution to the total pyrethroid exposure. The dietary 

exposure assessment performed in support of the pyrethroid cumulative was much more highly 

refined than that performed for prallethrin. In addition, for the prallethrin risk assessment, the 

most sensitive apical endpoint in the prallethrin database was selected to derive the POD. 

Further, the POD selected for prallethrin is specific to prallethrin, whereas the POD selected for 

the cumulative assessment was based on common mechanism of action data that are appropriate 
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for all 20 pyrethroids included in the cumulative assessment. Dietary exposure to prallethrin 

residues resulting from the proposed mosquito adulticide use over all crops will contribute very 

little to the dietary exposure to prallethrin alone; therefore, the proposed use will make an 

insignificant contribution to dietary risk to the pyrethroids as a whole.

9.0 Occupational Exposure/Risk Characterization

(M. Collantes, D407642, 8/9/2013 and D417631, 5/8/2014)

9.1 Occupational Handler Exposure/Risk Estimates

No chemical-specific data were submitted in support of this action. It HED’s policy to use the 

best available data to assess handler exposure. Sources of generic handler data, used as surrogate 

data in the absence of chemical-specific data, include studies from Pesticide Handler Exposure 

Database (PHED) 1.1, the Agricultural Handler Exposure Task Force (AHETF) database or other 

registrant-submitted occupational exposure studies. Some of these data are proprietary (e.g., 

AHETF data), and subject to the data protection provisions of FIFRA. The standard values 

recommended for use in predicting handler exposure that are used in this assessment, known as 

“unit exposures,” are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate 

Reference Table,” which, along with additional information on HED policy on use of surrogate 

data, including descriptions of the various sources, can be found at the Agency website.

Refer to Table 3.3.a. for a complete use pattern description. The inputs for area treated were 

based on information in ExpoSAC Policy 9.1. 

This document provides the revised occupational HEDs for the proposed mosquito adulticide use 

of prallethrin. Only short-term exposures are expected for occupational handlers from this use. 

As mentioned before, for prallethrin the selected endpoints and PODs for dermal and inhalation 

risk assessment are based on clinical signs related to neurotoxicity. However, the HECs used for 

inhalation risk assessment were calculated based on portal of entry effects, which resulted in 

lower HEC values than those calculated for systemic effects. Therefore, the portal of entry 

HECs are protective of the systemic effects (including neurotoxicity) observed in the toxicology 

database. As a result, handler inhalation and dermal routes of exposure are not combined.

Occupational handler scenarios for aerial and truck-mounted fogger applications resulted in 

dermal and inhalation MOEs greater than their respective LOCs, (dermal MOE ≥ 100 and 

inhalation MOE ≥ 30) at baseline (i.e., single layer clothing, no gloves or respirator) and are not 

of concern. No additional PPE recommendations are needed on the labels. A summary of the 

occupational handler risk estimates is provided in Table 9.1.

The Multicide 2798 and 2922 labels specify the use of portable, motorized backpack equipment 

adjusted to deliver ULV particles of less than 100 microns. HED does not have unit exposure 

handler data for hand held fogging equipment. Therefore, chemical-specific data are needed to 

support this scenario, and constitute a data gap for prallethrin. These data need to be submitted 

under the Part 158 data requirements (Guideline 875.1400).
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Table 9.1. Occupational Handler Exposure Risk Estimates for Prallethrin

Exposure Scenario Crop or Target

Dermal Unit 

Exposure

(μg/lb ai)1

Inhalation Unit 

Exposure

(μg/lb ai)1

Maximum 

Application 

Rate2

(lb ai/A)

Area 

Treated 

Daily3

Dermal Inhalation

Mitigation Level Mitigation Level Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)6 MOE7

Mixer/Loader

Liquid for Aerial

Applications

Mosquito 

Control

220

(Baseline)

0.219

(Baseline)

0.00072

7,500 A 0.015 2,000 0.000015 810

Liquids for 

Groundboom

Applications

(surrogate for Truck 

Mounted Ground 

fogger)

3,000 A 0.006 5,100 0.000006 2,000

Applicator

Aerial Sprays

(ULV Wide Area)

Mosquito 

Control

2.08

(Engineering Controls)

0.0049

(Engineering 

Controls)

0.00072

7,500 A .0.00014 210,000

0.0000003.3

60,000

Airblast Sprays

(surrogate for Truck 

Mounted Ground 

Fogger)

1770

(Baseline)

4.71

(Baseline)

3,000 A 0.048 630

0.000128

47

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”; Level of mitigation: Baseline, PPE, Eng. Controls.

2 Based on registered or proposed label

3 Exposure Science Advisory Council best professional judgement .

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (80 kg).

5 Dermal MOE = Dermal NOAEL (30 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposures (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (80 kg).

7 Inhalation MOE = Inhalation HED (ventilation rate 8.3 L/m = 0.006 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
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9.2 Post-application Risk

9.2.1 Dermal Post-application Risk

There is potential for dermal post-application exposure to workers entering fields under the 

airspace receiving treatment with prallethrin. For purposes of estimating post-application dermal 

exposure, small vine climbing fruit was selected as the surrogate crop because its respective 

highest transfer coefficients represent the worst case exposure scenarios to account for the 

mosquito control practices. This dermal post-application exposure scenario resulted in MOEs 

significantly greater than the LOC (MOE ≥ 100) and are not of concern. 

Table 9.2. Occupational Post-application Non-Cancer Dermal Exposure and Risk Estimates for 

Prallethrin.

Crop/Site Activities Transfer Coefficient 

(cm2/hr) DFR1 Dermal Dose (mg/kg/day)2 MOE3

Small vine climbing 

fruit girdling 19,300 0.002 0.004 7,700

1 DFR = Application Rate × F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.25 and D = 0.10 per day 

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hr/day ×]  BW (80 kg).

3 MOE = POD (30 mg/kg/day) / Daily Dermal Dose. 

9.2.2 Inhalation Post-application Risk

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

assessment is not being performed for prallethrin at this time. If new policies or procedures are 

put into place, the Agency might revisit the need for a quantitative occupational post-application 

inhalation exposure assessment for prallethrin.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.
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10.0 References

D289335, Prallethrin: Human Health Risk Assessment for the Public Health Use of Mosquito 

Adulticides Containing Prallethrin, M. Collantes, G. Bangs, 11/21/2003

Uma Habiba, TXR# 0056729, Summary of Hazard and Science Policy Council (HASPOC) 

Meeting on July 25, 2013: Recommendations on Data Requirement for Immunotoxicity Studies 

for Synthetic Pyrethroid Pesticides, 8/12/2013

M. Perron, Prallethrin - Summary of Toxicology Science Advisory Council (ToxSAC) Meeting 

of April 25, 2013, 7/30/2013

E. Scollon, A. Lowit, D381210, Re-Evaluation of the FQPA Safety Factor for Pyrethroid 

Pesticides, 6/27/2011

D411615, Prallethrin. Petition to Amend the Section 3 Registration to Include Food Use of the 

Insecticide as a Mosquito Adulticide for the Fogging of Airspace Over and/or Near Agricultural 

Crop Fields. Summary of Analytical Chemistry and Residue Data, W. Drew, 7/24/2013 

D413314, Prallethrin Acute and Chronic Aggregate Dietary (Food and Drinking Water) 

Exposure and Risk Assessment for the Section 3 Registration Action to Include Use of the 

Insecticide as a Mosquito Adulticide for the Fogging Application Near Agricultural Crop Fields, 

D. Dotson, 6/18/2014

M. Collantes, D407642, Prallethrin. Occupational and Residential Exposure Assessment for 

Proposed Label Amendments For Mosquito Adulticide Vector Control, 8/9/2013

M. Collantes, D417631, Prallethrin. Addendum to the Occupational and Residential Exposure 

Assessment for Proposed Label Amendments for Mosquito Adulticide Vector Control Use, 

5/8/2014

He Zhong, D407324, Prallethrin Drinking Water Assessment for the New Use of Two 

Multicide® Fogging Concentrates 2798 and 2922 as Adult Mosquitocides in All Agriculture 

Crop Areas, 2/4/2013 

K. Whitby, D394576, Pyrethroid Cumulative Risk Assessment, 10/4/2011

 
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Appendices

Appendix A: Toxicology Profile

Appendix A.1. Toxicology Data Requirements

The requirements (40 CFR 158.340) for food use for prallethrin are in Table A.1. Use of the 

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

Table A.1. Toxicology Requirements for Prallethrin

Guideline Number and Toxicity Study Required Satisfied

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

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

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

870.2400 Primary Eye Irritation ............................................................

870.2500 Primary Dermal Irritation ......................................................

870.2600 Dermal Sensitization..............................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Sub-chronic (Rodent).....................................................

870.3150 Oral Sub-chronic (Non-Rodent).............................................

870.3200 21-Day Dermal ......................................................................

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

870.3465 90/28-Day Inhalation .............................................................

yes

yes

yes

no

yes

yes

yes

yes

-

yes

870.3700 Developmental Toxicity (Rodent) ........................................

870.3700 Developmental Toxicity (Non-rodent)...................................

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

yes

yes

yes

yes

yes

yes

870.4100 Chronic Toxicity (Rodent).....................................................

870.4100 Chronic Toxicity (Non-rodent)..............................................

870.4200 Oncogenicity (Rat).................................................................

870.4200 Oncogenicity (Mouse) ...........................................................

870.4300 Chronic/Oncogenicity............................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity: Bacterial reverse mutation assay.....................

870.5265 Mutagenicity: Reverse mutation assay...................................

870.5300 Mutagenicity: In vitro Mammalian Cell Assay......................

870.5375 Mutagenicity: In vitro Mammalian Cell Assay......................

870.5395 Mutagenicity: In vivo Cytogenetics .......................................

870.5550 Mutagenicity: Unscheduled DNA Synthesis..........................

 yes

no

yes

yes

yes

no

yes

yes

yes

yes

yes

yes

yes

yes

870.6100 Acute Delayed Neurotoxicity (Hen) ......................................

870.6100 90-Day Neurotoxicity (Hen)..................................................

870.6200 Acute Neurotoxicity Screening Battery (Rat) ........................

870.6200 90 Day Neuro. Screening Battery (Rat) .................................

870.6300 Developmental Neurotoxicity................................................

no

no

yes

yes

yes

-

-

yes

yes

no*

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

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

870.7800 Immunotoxicity.......................................................................

yes

no

yes

yes

-

noa

*A developmental neurotoxicity (DNT) is not available for prallethrin. However, EPA has determined that 

DNTs for pyrethroid insecticides do not adequately characterize potential susceptibility of the young. In 

2009, EPA stated that registrants who have not fulfilled requirements for the DNT may instead cite 6 

previously submitted pyrethroid DNT studies, rather than conducting a full new study.

a The requirement for the immunotoxicity study was waived by HED’s Hazard and Science Policy Council 

(HASPOC). 
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Appendix A.2 Toxicity Profile Tables

Table A.2.a. Acute Toxicity of Prallethrin Technical

GDLN Study Type MRID Results

Tox

Category

870.1100 Acute Oral 42030903 LD50: 640 mg/kg (♂)

 460 mg/kg (♀)

II

870.1200 Acute Dermal 41321812 LD50 > 5000 mg/kg (♂+♀) IV

870.1300 Acute Inhalation 42030904 

41321813

LC50: 288 mg/m3(♂)

 333 mg/m3(♀)

II

870.2400 Acute Eye Irritation 42030905

41321814

Minimally irritating III

870.2500 Acute Skin Irritation 42030905

41321814

Non-irritating IV

870.2600 Skin Sensitization 41321815 Not a sensitizer N/A

Table A.2.b. Subchronic, Chronic, and Other Toxicity

Guideline 

No.

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3100 Subchronic 

Feeding-Rat

MRID 41321816

42030906

0, 7.93, 24.0, 79.1, 230 

mg/kg/day (♂); 0, 8.96, 26.1, 

82.3, 244 mg/kg/day (♀)

NOAEL: 79.1 (♂), 82.3 (♀); LOAEL: 230 (♂), 244 

(♀), based on alopecia (days 1-2), decreased body 

weights, hematological & clinical chemistry changes, 

hepatocellular hypertrophy, increased # small follicles 

in thyroid.

870.3100 Subchronic Feeding 

- Mouse

MRID 42077004

0, 39, 374, 808, 1839 mg/kg/day 

(♂); 0, 47, 444, 890, 1884 

mg/kg/day (♀)

NOAEL: 374 (♂), 444 (♀); LOAEL: 808 (♂), 890 (♀), 

based on increases in liver weights, enlargement of 

hepatocytes, increases in cholesterol & creatinine 

levels.

870.3150 Subchronic Oral 

(Capsules) -Dog. 

MRID 41321817

42077001

0, 3, 10, 30 mg/kg/day

NOAEL: 3; LOAEL: 10, based on tremors (9th week), 

decreased A/G ratio, increased cholesterol &

phospholipids, enlarged livers.

870.3200 21-Day Dermal 

Toxicity-Rat

MRID 42999101

0, 30, 150, 750 mg/kg/day

NOAEL: 30; LOAEL: 150, based on clinical signs of 

toxicity (day 1) and decreases in body weight gain.

870.3465 28-Day Inhalation -

Rat

MRID 42030907

41321818

0, 0.0010, 0.0044, 0.019 mg/L; 4 

hr/day

NOAEL: 0.0010 mg/L; LOAEL: 0.0044 mg/L, based 

on irregular respiration, decreased spontaneous 

activity, salivation, incontinence, and nasal discharge.

870.3700 Oral Developmental 

Toxicity-Rat 

MRID 42030905

42077005

0, 10, 30, 100, 300 mg/kg/day

Maternal NOAEL: 10; Maternal LOAEL: 30, based on 

tremors (GD 9), salivation (GD 10), and

chromorrhinorrhea (GD 10)

Developmental NOAEL: 300 (HDT).
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Table A.2.b. Subchronic, Chronic, and Other Toxicity

Guideline 

No.

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3700 Subcutaneous 

Developmental 

Toxicity & 

Reproductive 

Parameters - Rat

MRID 41321820

0, 12.5, 25.0, 50.0 mg/kg/day

Maternal NOAEL: 25; Maternal LOAEL: 50,based on 

tremors (GD 9) and exaggerated reflexes (GD 9).

Developmental NOAEL: 50 (HDT).

Offspring NOAEL: 50 (HDT).

870.3700 Oral 

Developmental 

Toxicity-Rabbit

MRID 42030908

42899501

0, 10, 30, 100, 200 mg/kg/day

Maternal NOAEL: 30; Maternal LOAEL: 100, based 

on tremors from range-finding study: (GD 11).

Developmental NOAEL: 200 (HDT).

870.3700 Subcutaneous 

Developmental 

Toxicity - Rabbit

MRID 41321821

0, 1, 3, 10 mg/kg/day

Maternal NOAEL: 10 (HDT); LOAEL: 30, from 

range-finding study (mortality in nonpregnant 

animals).

Developmental NOAEL: 10 (HDT).

870.3800 Reproductive 

Toxicity - rat

MRID 42077006

42178501

0, 6, 31, 156, 329 mg/kg/day 

(♂); 0, 7, 37, 185, 375 

mg/kg/day (♀)

Parental/Offspring systemic NOAEL: 31 (♂), 37 (♀). 

LOAEL: 156 (♂), 185 (♀),based on decreased 

bodyweights, bodyweight gains, increased liver 

weights, microscopic findings in liver, kidney, thyroid, 

pituitary in parents; decreased pup bodyweights during 

lactation.

Reproductive NOAEL: 329 (♂), 375 (♀) (HDT).

870.4100 Chronic Oral 

(Capsule) - Dog

MRID 42077002

0, 2.5, 5, 10, 20 mg/kg/day

NOAEL: 2.5. LOAEL: 5, based on clinical signs of 

neurotoxicity-tremors (wk4), convulsions (wk19), 

convulsions, salivation, and rapid eye blinking (wk44). 

At 10: (trembling (wk 1), rapid eye blinking (wk 8), 

hunched posture (wk 12), panting (wk 11), and 

increased cholesterol, phospholipids, and AP were 

seen.

870.4300 Chronic 

toxicity/Carcinogenicity-Rat

MRID 41321819

42061401

0, 3.3, 16.3, 83.5 mg/kg/day 

(♂); 0, 4.0, 19.1, 103.4 

mg/kg/day (♀)

NOAEL: 83.5 (♂) (HDT), 19.1 (♀); LOAEL: 103.4

(♀),based on decreases in bodyweight gains and 

histiocytic infiltration in liver. 

No evidence of carcinogenicity

870.4200 CarcinogenicityMouseMRID 42077003

0, 13, 68, 347, 708 mg/kg/day 

(♂); 0, 16, 78, 384, 778 

mg/kg/day (♀)

NOAEL: 68 (♂), 778 (♀) (HDT); LOAEL: 347 (♂), 

based on kidney effects (increased weights, basophilic 

tubules, and amyloidosis).

870.5100 & 

870.5265

Gene Mutation -

Salmonella & E. 

Coli

MRID 41321822

Up to 5000 μg/plate with & 

without metabolic activation

Prallethrin did not induce any increases in reverse 

mutations in any of the bacterial strains tested.

870.5300 Forward Mutation 

Assay in Chinese 

Hamster Lung 

Fibroblasts

MRID 41321823

Up to cytotoxic levels (5 x 10-

5M concentration without 

metabolic activation (S9), 3 x 

10-4M concentration with 

metabolic activation).

Prallethrin did not induce a significant increase in 

forward mutations at the hypoxanthine-guanine 

phosphoribosyl transferase (HGPRT) locus in Chinese 

hamster lung (V79) cells.

870.5375 In vitro

chromosomal 

aberration study in 

Chinese Hamster 

Ovary (CHO K1) 

cells

MRID 42030910; 41321824

Up to cytotoxic levels (8 x 10-5

M without metabolic activation 

and 3 x 10-4M with metabolic 

activation

Prallethrin tested negatively at all doses without 

metabolic activation and tested positively at all doses 

with metabolic activation. It was not clearly doserelated but clastogenicity was seen at nontoxic and 

slightly toxic doses.
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Table A.2.b. Subchronic, Chronic, and Other Toxicity

Guideline 

No.

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.5395 Micronucleus Assay MRID 42999901

48, 95 or 190 mg/kg

Prallethrin had no effect on micronucleus formation in 

bone marrow cells up to a lethal dose. There was no 

bone marrow cytotoxicity.

870.5550

DNA Repair Assay MRID 42030912; 41321826

Single dose of 400 mg/kg

Prallethrin tested negatively for inducing unscheduled 

DNA synthesis in rat hepatocytes.

870.6200 Acute neurotoxicity 

- Rat

MRID 43343301

0, 30, 100, 300 mg/kg bw

NOAEL: 100; LOAEL: 300, based on reduced motor 

activity in both sexes and tremors and death in 

females.

870.6200 Subchronic 

neurotoxicity – Rat

MRID 43694501

0, 9.3, 74, 363 mg/kg/day (♂)

0, 11.1, 88, 420 mg/kg/day (♀)

NOAEL: 74 (♂), 88 (♀); LOAEL: 363 (♂), 420 (♀), 

based on decreases in bodyweight and food 

consumption. No indications of neuropathology, 

however, indications of higher arousal rate in females.

NonGuidelineWIL Laboratories 

Acute neurotoxicity 

comparison studyRat

MRID 48333801

0, 150, 250 or 400 mg/kg/day

NOAEL: 150; LOAEL: 250, based on clonic 

convulsions, flattened posture, splayed hind legs 

and/or slight to coarse tremors. Slightly to moderately 

impaired mobility, coarse tremors, ataxia, and impaired 

gait.

870.7485 Metabolism-Rat MRID 42030913; 41321827 Single labeled low or high dose or 14-day repeated low 

dose followed by a labeled low dose. Cis and transisomers rapidly absorbed, distributed, metabolized and 

excreted under all dosing regimens. Most of 

radioactivity recovered in urine and feces within 48 

hours for both sexes and isomers. Much greater 

proportion of trans isomer eliminated in urine than cis

isomer because of easier cleavage of ester linkage of 

trans-isomer by esterase. Cis isomer: urinary 

excretion minor compared to fecal. Females excreted 

greater proportion of radioactivity in urine than males 

for both isomers. Repeated dosing appears to induce 

metabolism (only 2% of parent found in feces). Low 

bioaccumulation. No sex differentiation in tissue 

distribution. Higher residue levels in kidneys and liver 

(both isomers) and blood (trans-isomer). Major 

metabolic pathway: ester cleavage.

Single low oral or subcutaneous dose. No differences 

in absorption, distribution, metabolism or excretion in 

rats dosed orally or subcutaneously. Major 

biotransformation reactions of cis and trans-isomers 

include: oxidation at the methyls of the isobutenyl 

group in the acid moiety and at the C-1 or C-2 

positions of the propynyl group in the alcohol moiety; 

cleavage of ester linkage; conjugation of hydroxy

derivatives with glucuronic acid and sulfuric acid.

870.7800 Immunotoxicity-Rat Study not required.
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Appendix A.3. Toxicological Doses and Endpoints for Use in Human Risk Assessment

Hazard Identification and Endpoint Selection 

Acute Reference Dose (aRfD) –All Populations Including Infants and Children and 

Females Age 13-49 

Study Selected: Chronic Dog

MRID #: 42077002

Dose and Endpoint for Risk Assessment: NOAEL is 2.5 mg/kg/day, based on neurotoxicity at 

the LOAEL of 5 mg/kg/day.

Uncertainty Factor:

Adults and Children ≥ 6 years old: 100x (1x FQPA, 10x interspecies extrapolation, 10x

intraspecies variability)

Acute RfD = 

100( )

2.5 /

UF

mg kg

= 0.025 mg/kg/day

Children < 6 years old: 300x (3x FQPA, 10x interspecies extrapolation, 10x intraspecies 

variability)
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Comments about Study/Endpoint: The chronic dog study was selected based on neurotoxic 

effects observed at the LOAEL of 5 mg/kg/day. For acute dietary risk assessment, the endpoint 

used is commonly based on adverse effects attributed to a single dose exposure. However, for 

prallethrin, it is based on neurotoxic effects initially observed at 4 weeks. For pyrethroid 

chemicals, the pharmacokinetics indicate that the onset of neurotoxicity is rapid, with the time to 

peak effect for neurobehavioral effects occurring within hours. This is followed by rapid 

metabolism and elimination that does not result in accumulation. Therefore, repeated dosing is 

essentially a series of acute exposures, and the effects seen in the dog study after 4 weeks are still 

appropriate for setting the aRfD. 

In the dog study, animals were given a bolus dose (capsule) of prallethrin once daily for 52 

weeks. The dogs were observed daily for clinical signs and mortality. At 4 weeks, trembling 

was observed in one dog at the LOAEL of 5 mg/kg/day. Although trembling was observed in 

only one dog on one occasion at the 5 mg/kg/day dose, there was a clear dose response for the 

effect. In the same dog, convulsions and tremors were seen at week 19. Convulsions, panting, 

salivation, rapid eye blinking, and muscle twitching were seen 5 hours after dosing prior to the 

death of the dog during week 44. Based on the toxicity profile for pyrethroids, clinical signs 

would be expected sooner than 4 weeks; however, it could have been easily missed due to the 

timing of the post-dosing clinical examination, since prallethrin has a rapid time to peak effect. 

At the next highest dose of 10 mg/kg/day, the incidence and frequency of trembling

substantially increased, with 5 dogs being affected on numerous occasions (over 40). 

Additionally, effects were seen much earlier (during 1 week). At 20 mg/kg/day, all dogs (8) 

were affected with increased frequency. At 10 and 20 mg/kg/day, the trembling was also 

accompanied by dose-related rapid eye blinking, hunched posture, salivation, and panting. 

Although the use of 5 mg/kg/day as a POD is a conservative approach, it is only 2 fold lower 

than where numerous clinical signs were observed (during week 1). The use of 5 mg/kg/day as 

the POD is supportable when all of the information is considered together (time to peak effect 

for prallethrin, dose response relationship at 5mg/kg/day, earlier onset of effects at 10 

mg/kg/day). Therefore, the chronic dog study was selected to protect for potential 

neurotoxicity. 

The developmental rat and rabbit, acute neurotoxicity, and WIL studies were all considered for 

risk assessment. However, higher NOAELs were determined in the acute rat (ACN and WIL) 

and developmental rat and rabbit studies, so they were not selected for risk assessment. The 

WIL FOB study and the ACN study both used high vehicle volumes which likely impacted 

absorption characteristics of prallethrin, thereby increasing the POD. Given what is known 

about pyrethroids’ toxicokinetics/dynamics in general, and since there is no apparent increase in 

hazard from repeated/chronic exposures to prallethrin, the acute dietary exposure assessment is 

protective of chronic dietary exposures.

Incidental Oral Exposure (Short-Term) 

Study Selected: Chronic Dog

Acute RfD = 

300( )

2.5 /

UF

mg kg

= 0.008mg/kg/day
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MRID #: 42077002

Dose and Endpoint for Risk Assessment: NOAEL is 2.5 mg/kg/day, based on neurotoxicity at 

the LOAEL of 5 mg/kg/day

Uncertainty Factor:

Adults and Children < 6 years old: 300X (3x FQPA, 10x interspecies extrapolation, 10x

intraspecies variability)

Comments about Study/Endpoint: The chronic dog study was selected based on neurotoxic 

effects initially observed at week 4. Signs of neurotoxicity (trembling, convulsions, heavy 

panting, salivation, rapid eye blinking, and muscle twitching) were observed in 1 dog at the 

LOAEL of 5 mg/kg/day. Additionally, neurotoxicity was seen within hours of dosing prior to 

the death of the animal during week 44 (see acute dietary). The NOAEL of 2.5 mg/kg/day is 

protective of potential offspring/developmental effects, as well as systemic effects, including 

neurotoxicity, observed in the toxicology database (See acute dietary risk assessment).

Dermal Exposure (Short-Term)

Study Selected: 21-Day Dermal Toxicity Study in Rats 

MRID No.: 42030907

Dose and Endpoint for Risk Assessment: The LOAEL=150 mg/kg/day, based on clinical 

signs (trembling, fixation, abnormal gait, sensitivity to stimuli, twitching, and writhing spasms) 

and body weight changes. The NOAEL is 30 mg/kg/day. 

Uncertainty Factor:

Adults and Children ≥ 6 years old: 100X (1x FQPA, 10x interspecies extrapolation, 10x

intraspecies variability)

Children < 6 years old: 300X (3x FQPA, 10x interspecies extrapolation, 10x intraspecies 

variability)

Comments on Study/Endpoint/UFs: The dermal rat study was selected based on neurotoxic 

effects (trembling, fixation, abnormal gait, sensitivity to stimuli, twitching, and writhing spasms) 

and body weight changes observed at the LOAEL of 150 mg/kg/day. The NOAEL is 30 

mg/kg/day. The POD and endpoint are considered appropriate for short-term risk assessment 

since it is a route specific study, the endpoint is based on the effect of concern, and there is no 

evidence of developmental toxicity or increased susceptibility.

Inhalation Exposure (Short-Term)

Study Selected: Inhalation Toxicity Study in Rats 

MRID No.: 42030907

Dose and Endpoint for Risk Assessment: The LOAEL=0.0044mg/L, based on irregular 

respiration, decreased spontaneous activity, salivation, incontinence, and nasal discharge. The 

NOAEL is 0.001mg/L. 
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Uncertainty Factor: Adults and Children ≥ 6 years old: 100X (1x FQPA, 3x interspecies 

extrapolation, 10x intraspecies variability)

Children < 6 years old: 300x (3x FQPA, 3x interspecies extrapolation, 10x intraspecies 

variability).

Comments on Study/Endpoint/UFs: In a 28-day inhalation toxicity study in rats, nasal 

discharge, irregular respiration, decreased spontaneous activity, salivation, and incontinence 

were seen at the LOAEL of 0.004 mg/L. The NOAEL is 0.001 mg/L. Human equivalent 

concentrations (HECs) and doses were calculated and used for risk assessment (see values below 

and section A.4 for calculations). For inhalation risk assessment, both portal of entry and 

systemic HECs were calculated for prallethrin, based on the effects observed in the inhalation 

study. The portal of entry HEC was significantly lower (15x) than the systemic HEC; therefore, 

the portal of entry HEC was used for risk assessment, and it is considered protective of the 

systemic effects observed in the inhalation study. 

Human Equivalent concentrations (HECs) 

and Human Equivalent Doses (HEDs) for 

Prallethrin 

HECs HEDs

Occupational ventilation rate= 8.3 L/min 0.00010 mg/L 0.006 mg/kg/day

ventilation rate= 16.7 L/min 0.012 mg/kg/day

ventilation rate= 29 L/min 0.020 mg/kg/day

Residential Handler/Outdoor Post-application 0.00020 mg/L 0.006 mg/kg/day

Indoor Post-application without 

air ventilation

0.00014 mg/L N/A*

Indoor Post-application with air 

ventilation

Adults: 0.00004 mg/L

Children: 0.00003 mg/L

N/A*

Bystander 0.00002 mg/L N/A*

*MOEs calculated directly from HECs. 

Based on the exposure profile, HED does not anticipate long-term inhalation exposure for adults 

or children.
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Appendix A.4. Human Equivalent Analysis

The methods and dosimetry equations described in EPA’s reference concentration (RfC) 

guidance (1994) and OPP’s guidance on the application of the RfC methodology (2014) are 

suited for calculating HECs based on the inhalation toxicity NOAEL for use in MOE 

calculations. The regional-deposited-dose ratio (RDDR), which accounts for the particulate 

diameter (mass median aerodynamic diameter [MMAD] and geometric standard deviation [g] 

of aerosols), can be used to estimate the different dose fractions deposited along the respiratory 

tract. The RDDR is also based on interspecies differences in ventilation and respiratory-tract 

surface areas. Thus, the RDDR can be used to adjust an observed inhalation particulate exposure 

of an animal to the predicted inhalation exposure for a human.

RDDR for Prallethrin 

In the 28-day rat inhalation study, prallethrin was administered to 10/sex Sprague Dawley rats, 4 

hours/day, 5 days/week, as an aerosol with an average mass medium aerodynamic diameter 

(MMAD) of 3.77 and a geometric standard deviation (σ) of 1.30. The LOAEL of 0.0044 mg/L 

is based on nasal discharge, irregular respiration, decreased spontaneous activity, salivation, and

incontinence. The NOAEL is 0.001 mg/L. 

Because the respired material used in the inhalation study is an aerosol, the RDDR ratio, which 

incorporates MMAD and σ, is appropriate to use for HEC calculation (table below). The 

“RDDR.exe” software program was used to obtain the RDDR value of 0.201 based on 

extrathoracic portal of entry effects (POE)(Figure A.4.1). The RDDR selected and the resulting 

HEC was significantly lower than the systemic RDDR and resulting HEC. Therefore, the POE 

HEC is protective of systemic effects. The inputs for the program are: MMAD=3.77; σ=1.30; 

body weight for Sprague Dawley Rats: 236g; Standard human body weight information: 70 kg.
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Figure A.4.1. Regional Deposited Dose Ratios (RDDR) for Prallethrin

Calculation of the Human Equivalent Concentration (HEC) and Human Equivalent Dose

Human Equivalent Concentrations

Occupational HEC (Handler) = 0.00010 mg/L

POD (0.001mg/L) x RDDR (0.201) x daily duration (4hr/8hr) x weekly duration (5 days/5days)

Residential HEC (Handler) = 0.0002 mg/L

POD (0.001mg/L) x RDDR (0.201) x daily duration (4hr/4hr) x weekly duration (5 days/5days)

Adult Residential HEC (Indoor post-application with ventilation) = 0.00004 mg/L

POD (0.001mg/L) x RDDR (0.201) x daily duration (4hr/16hr) x weekly duration (5days/7days)

Children Residential HEC (Indoor post-application with ventilation) = 0.00003 mg/L

POD (0.001mg/L) x RDDR (0.201) x daily duration (4hr/18hr) x weekly duration (5days/7days)

Residential HEC (Indoor-without ventilation) = 0.00014 mg/L

POD (0.001mg/L) x RDDR (0.201) x daily duration (not applicable) x weekly duration (5hr/7hr)

Residential HEC (Bystander) = 0.00002 mg/L

POD (0.001mg/L) x RDDR (0.201) x daily duration (4hr/24hr) x weekly duration (5days/7days) 

Human Equivalent Doses

Using the calculated HECs, a conversion of the inhalation concentration to a dose (mg/L to 

mg/kg/day) was conducted as follows: dose (systemic HEC value) mg/L x A (absorption) x CF 

(conversion factor) L/hr/kg) x D (duration-hours) x AF (activity factor) = mg/kg/day.
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Human Equivalent Doses (HEDs)

Occupational 

Scenarios with ventilation rates of 8.3 L/min: 

HED= 0.00010mg/L x 1 x 11.8 x 8 x 0.6 = 0.006 mg/kg/day

Scenarios with ventilation rates of 16.7 L/min 

HED=0.00010mg/L x 1 x 11.8 x 8 x 1.2 = 0.012 mg/kg/day

Scenarios with ventilation rates of 29 L/min 

HED= 0.00010mg/L x 1 x 11.8 x 8 x 2.1 = 0.020 mg/kg/day

Residential (Handler and Outdoor Post-application)

HED =0.00020 mg/L x 1 x 11.8 x 2 x 1.2 = 0.006 mg/kg/day

For residential indoor post-application and bystander exposure, margins of exposure were 

calculated directly from the HECs.
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Appendix A.5. Pyrethroid Cumulative Screen

The Agency is required to consider the cumulative risks of chemicals sharing a common 

mechanism of toxicity. The Agency has determined that the pyrethroids and pyrethrins share a 

common mechanism group (http://www.regulations.gov; EPA-HQ-OPP-2008-0489-0006). The 

members of this group share the ability to interact with voltage-gated sodium channels ultimately 

leading to neurotoxicity. The cumulative risk assessment (CRA) for the pyrethroids/pyrethrins 

was published on Nov. 9, 2011 (USEPA, 2011a) and is available at http://www.regulations.gov; 

EPA-HQ-OPP-2011-0746. No cumulative risk estimates of concern were identified, allowing 

the Agency to consider new uses for pyrethroid actives. For information regarding EPA’s efforts 

to evaluate the risk of exposure to pyrethroids, refer to 

http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html.

Although the active ingredient, prallethrin, was included in the initial common mechanism 

grouping (CMG) science policy document from 2008, the registered use on turf was not assessed 

in the November 2011 pyrethroid cumulative risk assessment. However, the Agency has 

determined, based on its chemical structure and based on the observation of neurobehavioral 

effects consistent with Type II pyrethroids, that prallethrin should be included in the CMG for 

this class of pesticides. As such, the Agency must consider the potential contribution of 

prallethrin to the cumulative risk assessment. As part of the assessment for the registered 

prallethrin turf uses, the Agency has performed an analysis to determine if the use will 

significantly contribute to or change the overall findings in the pyrethroid CRA.

Cumulative Hazard Assessment: Relative Potency Estimation for Prallethrin

The 2011 pyrethroid CRA relies on the relative potency factor (RPF) approach using 

administered dose as the metric for quantifying chemical potency. In the RPF approach, the 

toxic potency of each chemical in the common assessment group (CAG) is determined. One 

member of the CAG is selected as the index chemical that is used as the point of reference for 

standardizing neurobehavioral potency of the other members of the CAG. In order to develop 

such potency estimates, EPA prefers to use a uniform measure of toxicity. In other words, the 

Agency prefers to use data that are from the same endpoint and same duration and to the extent 

possible any other factors that affect potency (e.g., time to peak effect, sex, etc).

In the pyrethroid CRA, the Agency used the two special WIL Functional Observational Battery 

(FOB) studies for estimating relative potency. These studies were selected because they 

examined many behaviors, including key ones for evaluating neurotoxicity specific to 

pyrethroids. Specifically, the studies looked at a number of key parameters that are directly 

relevant to the Type I (e.g., hyperthermia tremors and clonus) and Type II (e.g., hypothermia, 

salivation, and mobility) syndromes. In addition to the WIL FOB studies, there is another study 

(Wolansky et al, 2006) that provides a high quality data set for estimating relative potency. 

Whereas the WIL FOB studies focus on endpoints specific to pyrethroid toxicity syndromes, the 

Wolansky study measured motor activity. Motor activity is considered an apical endpoint 

because it measures alterations in the activity level of an intact rat. Although the Wolansky 

study provides a potential data source for a uniform measure of potency, it was not utilized in the 
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CRA because of the lack of specific relevance to the common mechanism of action for the 

pyrethroids. 

In the CRA, deltamethrin was used as the index chemical. The RPFs used for the CAG in the 

pyrethroid screening level cumulative were determined by dividing the chemical-specific 

BMD20 by the BMD20 of the index chemical, deltamethrin. A RPF of 0.10 was used to 

quantify comparative exposures from the registered prallethrin turf use. 

Cumulative Exposure and Risk Issues

In order to determine if the registered prallethrin turf use will significantly contribute to or 

change the overall findings in the pyrethroid CRA the Agency performed a quantitative exposure 

and risk assessment. This assessment used the prallethrin RPF as well as the same exposure 

algorithms and inputs that were used in the 2011 pyrethroid CRA.

MOEs calculated and presented in Appendix Table A.5.a were compared with the MOEs 

currently driving turf exposures and risks in Table 6.4.7a from the 2011 pyrethroid CRA. The 

routes of exposure include handler and post-application dermal for adults, and post-application 

dermal and incidental oral for children. Quantitative post-application inhalation exposures from 

the turf use are not included in the CRA because this is not a significant route of exposure. 

Handler dermal exposures and risks resulting from use of a pyrethroid on turf are currently 

driven by the cyfluthrin turf use pattern (i.e., mixing/loading/applying emulsifiable concentrate 

using hose-end sprayer) with an MOE of 9,200, which is lower than the MOE of 540,000

estimated for adult dermal exposure from the registered prallethrin turf (i.e., mixing/loading/ 

applying microencapsulated using hose-end sprayer). Dermal post-application exposure and risk 

estimates for adults and children < 6 years old are currently driven by the cyfluthrin turf use 

pattern with adult and children < 6 years old dermal MOEs of 4,500 and 3,000, respectively, both 

of which are lower than the estimated MOEs for prallethrin (220,000 and 150,000, respectively). 

For children < 6 years old, hand-to-mouth post-application exposure and risk estimates are 

currently driven by the cyfluthrin turf pattern with an MOE of 21,000, which is less than the 

estimated MOE for prallethrin (1,100,000). A summary of these MOEs is presented in Appendix 

Table A.5.a while the detailed calculations are presented in Appendix Table A.5.b. In all cases, 

the estimated prallethrin MOEs using the RPF method were higher (i.e., less of a risk concern) 

than those used in the 2011 pyrethroid CRA. Thus, the Agency has determined that the proposed 

prallethrin turf use will not significantly contribute to or change the overall findings in the 2011 

pyrethroid CRA.
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Table A.5.a. Prallethrin Screening Level “Cumulative” Combined Exposure and Risk from the 

Registered Turf Use

Chemical Exposure 

Scenario

Route of 

Exposure Population MOE Combined MOE

Registered

Use Prallethrin Turf/Lawn

Handler Dermal –

Hose-end Sprayer Adult

520,000 NA

Post-Application 

Dermal 220,000 NA

Post-Application 

Dermal Children 

(< 6 years old)

150,000

130,000 Post-Application 

Incidental Oral 1,100,000

CRA Cyfluthrin Turf/Lawn

Handler Dermal –

Hose-end Sprayer Adult

9,200 NA

Post-Application 

Dermal 4,500 NA

Post-Application 

Dermal Children 

(< 6 years old)

3,000

2,700 Post-Application 

Incidental Oral 21,000
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Table A.5.b. Prallethrin Screening Level “Cumulative” MOEs

Turf Handler Exposure

Exposure 

Scenario

Application 

Rate

(lb ai/A)

Amount 

Treated 

Daily (A)

Baseline 

Dermal 

Unit 

Exposure 

(mg/lb ai)

Baseline 

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Baseline Dermal 

Exposure 

Baseline 

Inhalation 

Exposure 

Baseline 

Dermal Dose

Adjusted 

Baseline 

Dermal Dose

(mg/kg/day) a

Adjusted 

Baseline 

Dermal 

MOE b

Baseline 

Inhalation 

Dose

Adjusted 

Baseline 

Inhalation 

Dose

(mg/kg/day)

Baseline 

Inhalation MOE

Combined 

MOE

Turf Dermal

(adults) 0.045 0.5 13.4 0.022 0.30 0.0005 0.0002 0.00002 520,000 7.07E-6 6.84E-7 15,000,000 500,000

Turf Post-application Hand-to-Mouth Exposure

Exposure 

Scenario Faihands

1-2 yr old 

Dermal 

Exposure

SAH

(cm2)

HRt

(mg/cm2)

FM

Exposure 

Time 

(hours/day)

N_Replen SE Freq_HtM

BW

Average 

Daily Dose

(mg/kg/day)

Adjusted Dose 

(mg/kg/day) a

Adjusted 

MOE b

Fraction of Hand 

Surface Area 

Mouthed / Event

Number of 

replenishment 

intervals per hr 

(intervals/hr)

Extraction by 

Saliva

H-t-M 

events per 

hour

Hand to 

Mouth

(1 < 2 year 

olds)

0.034 0.168 150 1.834E-05 0.13 0.9 4 0.5 13.9 11.4 1.0E-4 9.99E-6 1,100,000

Turf Post-application Dermal Exposure

Exposure 

Scenario Application Rate

(lb ai/A)

Body Weight

(kg)

Exposure Time 

(hours)

Conversion 

Factor 

(mg/ug)

TTR (ug/cm2)

c Transfer Coefficient 

(cm2/hr)

Absorbed Dermal Dose 

(mg/kg/day)

Adjusted Dose 

(mg/kg/day) a

Adjusted 

MOE b

Turf Dermal

(< 6 year olds) 0.045

11.4 0.9

0.001 0.0108

37,000 0.00071 6.86E-5 150,000

Turf Dermal

(adults) 71.8 1.1 130,000 0.00048 4.67E-5 220,000

a. Doses were adjusted based on an estimated prallethrin RPF of 0.10.

b. MOEs were calculated by comparing the adjusted dose to the oral BMD20 from the WIL FOB data for the index chemical, deltamethrin (14.5 mg/kg/day).

c. Cyfluthrin TTR was used for all chemicals that did not have TTR data since cyfluthrin had the highest value.
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Appendix B. Physical/Chemical Properties

Table B.1. Physicochemical Properties of Prallethrin

Parameter Value Reference

Melting point/range -25oC (Liquid at room temperature). Sumitomo Chemical MSDS 

(23 May 2010)

Boiling point (at 760 mm Hg) 313.5oC WHO Specification 743/TC 

(November 2004)

pH (at 20°C) 3.22 Sumitomo Chemical MSDS 

Density (at 20oC) 1.03 g/mL (23 May 2010)

Water solubility (mg/L at 25oC, pH 

5.5-5.6)

8.03 WHO Specification 743/TC 

(November 2004)

Solvent solubility (20-25°C) Miscible with most organic solvents. Sumitomo Chemical MSDS 

(23 May 2010)

Vapor pressure (at 25oC) 4.2 x 10-3 Pa (3.2 x 10-5 mm Hg) Petition #2F8090

Dissociation constant, pKa Not applicable (does not dissociate). WHO Specification 743/TC 

Octanol/water partition coefficient, (November 2004)

Log KOW (at 25°C, pH 5.6-5.9)

4.49

UV/visible absorption spectrum Not available.
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Appendix C. Review of Human Research

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

intentionally exposed to a pesticide or other chemical. These data are subject to ethics review 

pursuant to 40 CFR 26, have received that review, and are compliant with applicable ethics 

requirements. For certain studies, that review may have included review by the Human Studies 

Review Board. Descriptions of data sources as well as guidance on their use can be found at 

http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.
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Appendix D. Aggregate Risk Calculations

The following equations were used to calculate the risk estimates provided in Table 7.2 of the 

Short-Term Aggregate Risk Estimates Section

MOE = NOAEL/Exposure

MOE = 1 ÷ [1/MOEoral + 1/MOEdermal] 

Short-term Aggregate Risk for Children <6

For the population subgroups comprised of children, the most highly exposed subgroup was 

Children 1-2.

The incidental oral (hand-to-mouth) exposure for Children 1-2 is added to the background 

dietary exposure to arrive at the total oral exposure estimate.

Dietary Exposure + Incidental Oral Exposure = 0.000581 + 0.000685 = 0.001266 mg/kg/day

MOEoral = Oral NOAEL/Oral Exposure = 2.5/0.001266 = 1975

MOEdermal = 897.65

Total Aggregate MOE = 1 ÷ [1/MOEoral + 1/MOEdermal] 

Total Aggregate MOE = 1 ÷ [1/1,975 + 1/897.65]

Total Aggregate MOE for Children 1-2 = 620

For adults, the only oral exposure is the background dietary exposure from food and drinking 

water. This exposure is combined with post-application dermal exposure. The same equations 

used above are used to determine the adult total MOE.

MOE = 1 ÷ [1/MOEdietary + 1/MOEdermal] 

MOEdietary = NOAEL/Dietary Exposure
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Short-term Aggregate Risk for the general U.S. population:

MOEdietary = NOAEL/Dietary Exposure = 2.5/0.000155 = 16,129

MOEdermal = 1,777

Total Aggregate MOE = 1 ÷ [1/MOEdietary + 1/MOEdermal] 

Total Aggregate MOE = 1 ÷ [1/1,629 + 1/1,777]

Total Aggregate MOE for the General U.S. Population = 1,600 

Short-term Aggregate Risk for Females 13-49:

MOEdietary = NOAEL/Dietary Exposure = 2.5/0.000110 = 22,727

MOEdermal = 1,777

Total Aggregate MOE = 1 ÷ [1/MOEdietary + 1/MOEdermal] 

Total Aggregate MOE = 1 ÷ [1/22,727 + 1/1777]

Total Aggregate MOE for Females 13-49 = 1,600