UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: 10/10/2014 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: Deltamethrin. Human Health Risk Assessment for the Proposed Use of 

Deltamethrin Without U.S. Registration on Finfish 

PC Code: 097805 

Decision No.: 478936 

Petition No.: 3£8178 

DP Barcode: 0413048 

Registration No.: NA 

Regulatory Action: Tolerance Without U.S. 

Risk Assessment Type: Single Chemical 

Aggregate 

Case No.: 7414 

Registration 

TXRNo.: NA 

MRJDNo.:NA 

CAS No.: 52918-63-5 

40 CFR: §180.435 

FROM: Douglas A. Dotson, Ph.D., Chemist j}. /)~ 

Jaime D'Agostino, Ph.D., Toxico ogist }t~d t-. Margari

William 

ta 

Drew

Collantes, 

, Chemist 

M.S., 

~~~

.J?iologist '7/l 

:~ .... 

{~ 

., 

Risk Assessment Branch ff"v r; V"'C? V"'V 

Health Effects Division (7509P) ~ 

THROUGH: Karl

Michael 

yn Middleton, 

Doherty, Ph.D.

Toxicologist 

, Senior Che 

, 

ist 

~ 

~""} 

Zaida Figueroa, M.S., Industrial Hygienist · 

Christina Swartz, Branch Chie 

Risk Assessment Branch II 

Health Effects Division (7509P) 

P.V. Shah, Ph.D., Toxicolo ist 

Jeff Dawson, Chemist 

HED Risk Assessment Revi 

TO: Olga Odiott!Mark Suarez, PM Team 13 

Insecticide Branch (IB) 

Registration Division (7505P) 
Deltamethrin Human Health Risk Assessment DP No. D413048 

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

human health risk assessment for the proposed tolerance, without U.S. registration, for residues 

of the insecticide deltamethrin on finfish. 

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

incorporates updated endpoints for risk assessment as well as the most recent data and 

assumptions for conducting residential and occupational exposure assessments. No risks of 

concern were identified. 

Page 2 of64 
Deltamethrin Human Health Risk Assessment DP No. D413048

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Table of Contents

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

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

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

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

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

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

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

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

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

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

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

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

3.3 Pesticide Use Pattern..................................................................................................... 10

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.................................................................. 14

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

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

4.3.1 Pharmacokinetics...................................................................................................... 17

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

4.3.3 Critical Duration of Exposure................................................................................... 20

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 ........................................................................................ 22

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ........... 22

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

4.5 Toxicity Endpoint and Point of Departure Selections .................................................. 24

4.5.1 Dose-Response and Hazard Assessment .................................................................. 24

4.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment ........... 26

4.5.3 Cancer Classification and Risk Assessment Recommendation................................ 26

4.5.4 Summary of Points of Departure and Toxicity Endpoints ....................................... 27

5.0 Dietary Exposure and Risk Assessment ........................................................................... 27

5.1 Metabolite/Degradate Residue Profile.......................................................................... 27

5.1.1 Summary of Plant and Animal Metabolism Studies................................................. 28

5.1.2 Summary of Environmental Degradation ................................................................. 28

5.1.3 Comparison of Metabolic Pathways......................................................................... 29

5.1.4 Residues of Concern Summary and Rationale.......................................................... 29

5.2 Food Residue Profile..................................................................................................... 29

5.3 Water Residue Profile ................................................................................................... 30

5.4 Dietary Risk Assessment .............................................................................................. 30

5.4.1 Description of Residue Data Used in Dietary Assessment....................................... 31

5.4.2 Percent Crop Treated Used in Dietary Assessment .................................................. 32

5.4.3 Acute Dietary Risk Assessment................................................................................ 32
Deltamethrin Human Health Risk Assessment DP No. D413048

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5.4.4 Chronic Dietary Exposure Assessment..................................................................... 33

5.4.5 Summary Table......................................................................................................... 33

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ................................... 33

6.1 Residential Handler Exposure/Risk Estimates for Registered Uses............................. 33

6.2 Residential Post-Application Exposure/Risk Estimates for Registered Uses............... 36

6.3 Residential Risk Estimates for Use in Aggregate Assessment ..................................... 39

6.4 Residential Bystander Post-Application Inhalation Exposure...................................... 40

6.5 Spray Drift .................................................................................................................... 40

7.0 Aggregate Exposure/Risk Characterization...................................................................... 40

7.1 Acute Aggregate Risk................................................................................................... 41

7.2 Short-Term Aggregate Risk Estimates......................................................................... 41

8.0 Cumulative Exposure/Risk Characterization.................................................................... 41

9.0 Occupational Exposure/Risk Characterization ................................................................. 43

10.0 References......................................................................................................................... 43

Appendix A. Toxicology Profile.................................................................................................. 47

A.1 Toxicology Data Requirements .................................................................................... 47

A.2 Toxicity Profile Tables ................................................................................................. 48

A.3 Toxicological Doses and Endpoints for Use in Human Risk Assessments.................. 54

A.4 Pyrethroid Cumulative Screen ...................................................................................... 58

Appendix B. Physical/Chemical Properties................................................................................. 63

Appendix C. Review of Human Research ................................................................................... 64
Deltamethrin Human Health Risk Assessment DP No. D413048

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1.0 Executive Summary

Deltamethrin (1R,3R)-R-cyano(3-phenoxyphenyl)methyl 3-(2,2-dibromoethenyl)-2,2-

dimethylcyclopropanecarboxylate) is a broad-spectrum pyrethroid insecticide that is registered in 

the U.S. for direct application to a wide variety of food/feed crops, for use on stored grains, and 

for use in food/feed handling establishments (FHEs). Numerous formulations of deltamethrin 

are also registered for use in commercial and residential outdoor and indoor sites, as well as in 

paint additive and pet products. Pharmaq AS proposed a tolerance without U.S. registration for 

residues of deltamethrin in finfish, resulting from its use to control fish lice in farmed fish. 

There are no new residential uses associated with this regulatory action; however, a revised 

assessment of the registered residential uses is provided for the purpose of updating the 

aggregate risk assessment.

Pyrethroids have historically been classified into two groups, Type I and Type II, based on 

chemical structure and toxicological effects. Pyrethroids disrupt the voltage-gated sodium 

channels in the nervous system, resulting in neurotoxicity. Deltamethrin is a Type II pyrethroid.

Neurotoxicity was observed throughout the database and clinical signs characteristic of Type II 

pyrethroids, such as increased salivation, altered mobility/gait, and tremors, were the most 

common effects observed. Other observed neurotoxic effects included increased sensitivity to 

external stimuli, abnormal vocalization, and decreased fore- and hind-limb grip strength.

The database of deltamethrin experimental toxicology studies is largely complete and provides a 

robust characterization profile for children 6 years old and older, as well as for adults. In 

addition to the standard guideline studies, numerous studies from the scientific literature that 

describe the pharmacodynamic and pharmacokinetic profile of the pyrethroids in general have 

been considered in this assessment. Many of these studies were conducted with deltamethrin. A 

28- or 90-day inhalation study was not available, but the requirement for this study was waived 

by HED’s Hazard and Science Policy Council (HASPOC). In addition, there are ongoing efforts 

to develop data in juvenile rats to gain more information concerning the potential sensitivity of 

infants and young children to pyrethroids as a class. Despite the missing studies and the ongoing

scientific efforts, HED is confident that it has chosen endpoints, points of departure, and 

uncertainty factors that are protective for all populations, including infants and children.

Deltamethrin is rapidly absorbed following an oral dose, and effects are typically observed 

within two to five hours after dosing. For pyrethroids, as a class, the combination of rapid 

absorption, metabolism, and elimination precludes accumulation and increased potency 

following repeated dosing. This is also true of deltamethrin. No observed adverse effect levels 

(NOAELs) for the acute and chronic studies are similar, and the acute endpoint is protective of 

the endpoints from repeat dosing studies. Thus, for purposes of endpoint selection and exposure 

assessment, only single-day risk assessments need to be conducted.

There were no indications of fetal toxicity in any of the guideline studies. Evidence of increased 

juvenile qualitative sensitivity was observed in the developmental neurotoxicity and 2-generation 

reproduction studies. These observations are consistent with the findings of juvenile sensitivity 

in the literature for deltamethrin. However, the observations of increased sensitivity were at 

doses that were considered to be relatively high (i.e., near lethal doses), whereas at doses near the 
Deltamethrin Human Health Risk Assessment DP No. D413048

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point of departure, no effects on parental animals or offspring were observed in either the 

developmental neurotoxicity (DNT) or 2-generation reproduction study and, therefore, there is 

no susceptibility at these doses. The Agency has retained a 3X uncertainty factor to protect for 

exposures of children <6 years of age based on increased quantitative susceptibility seen in 

studies on pyrethroid pharmacokinetics (primarily conducted with deltamethrin) and the 

increased quantitative juvenile susceptibility observed in high dose guideline and literature

studies with deltamethrin and other pyrethroids.

The Wolansky et al. acute oral study (2006), in which decreased motor activity was observed, 

provides the most robust data set for extrapolating risk from exposure to deltamethrin. The dose 

used for risk assessment was determined using a benchmark dose (BMD) analysis using 1 

standard deviation from the control group as the benchmark response (BMR) as suggested for 

continuous endpoints in the Agency’s BMD guidance (USEPA 2012). The Wolansky acute 

study, endpoint, and dose were used for all dietary (acute), non-occupational (incidental oral and 

inhalation), and occupational exposure (inhalation) scenarios because it was the most robust data 

set for extrapolating risk from deltamethrin, and there is a lack of increased hazard from 

repeated/chronic exposure to deltamethrin. A dermal risk assessment was not conducted based 

on the lack of effects in a 21-day dermal study and low potential for dermal absorption for 

deltamethrin. These findings are consistent with the toxicology profile of many pyrethroids. 

HED has characterized deltamethrin as “not likely to be carcinogenic to humans” in accordance 

with the EPA Final Guidance for Carcinogen Risk Assessment (3/29/2005).

Adequate residue data are available for the purpose of evaluating risk from the use of 

deltamethrin on finfish. Following treatment of finfish to deltamethrin at the maximum 

allowable concentration, residues were below the level of quantification (LOQ) of 0.01 ppm in 

all samples of finfish muscle with skin and finfish liver.

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

chronic dietary risk for this insecticide because of a lack of increased toxicity with increased 

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

exposure require estimates of chronic dietary exposure (i.e. background from food and water) 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 acute risk estimates are below HED’s level of 

concern for all population subgroups, including those comprised of infants and children. As 

percent crop treated estimates were used for some commodities, the risk estimates are being 

reported at the 99.9th percentile of exposure. Although a chronic dietary endpoint was not 

required for deltamethrin, a chronic dietary exposure assessment was performed to provide 

background exposure for aggregation with residential exposure. 

There are no new proposed residential uses associated with this action. However, this document 

includes a revised handler and post-application exposure assessment for existing residential use 

scenarios (i.e., indoor, outdoor, pet collar, and paint additive) to reflect updates to HED’s 2012 
Deltamethrin Human Health Risk Assessment DP No. D413048

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Residential SOPs, policy changes for body weight assumptions, updated inhalation and 

incidental oral toxicological endpoints and uncertainty factors (UFs). These use scenarios are 

representative of all residential scenarios associated with deltamethrin products. 

All the residential handler scenarios resulted in inhalation risk estimates that are not of concern, 

i.e., the margins of exposure (MOEs) are greater than or equal to the level of concern (LOC) of 

100 (in this case). Post-application inhalation exposure for adults and children is anticipated to 

be negligible for the representative residential registered uses; therefore, a quantitative postapplication inhalation exposure assessment was not performed.

All the representative indoor/outdoor and pet collar residential use scenarios resulted in 

incidental oral (hand-to-mouth) post-application risk estimates for children ranging from an 

MOE of 630 to an MOE of 400,000 and are not of concern, as all MOEs were greater than the 

incidental oral LOC of 300. 

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 exposure (food + drinking water) and residues resulting from 

residential exposure. For adults, residential exposure consists of post-application inhalation 

exposure and for children, residential exposure consists of incidental oral (hand-to-mouth)

transfer. The short-term aggregate risk estimates are not of concern for adults or children.

Deltamethrin was included in a cumulative risk assessment for pyrethrins and pyrethroids (CRA, 

D394576, K. Whitby, 10/4/2011). Typically, proposed new residential uses of pyrethroid 

chemicals are evaluated to determine whether they would contribute significantly to or change 

the overall findings of the CRA.

Since the 2011 CRA, no new residential uses have been proposed for deltamethrin. Therefore, 

the current tolerance evaluation and the currently registered residential uses for deltamethrin will 

have no impact on the residential component of the cumulative risk estimates. The revised point 

of departures (PODs) selected for deltamethrin are specific to deltamethrin, whereas the PODs

selected for the cumulative assessment were based on common mechanism of action data that are 

appropriate for all 20 pyrethroids included in the cumulative assessment.

There are no occupational scenarios associated with the proposed tolerance on imported fish; 

therefore, an occupational exposure assessment is not required for this action.

There are no human health risk concerns associated with the proposed use. HED does not object 

to the establishment of a tolerance of 0.01 ppm for residues of deltamethrin in or on finfish.

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

assessment to the extent possible. The assessment resulted in no risks of concern.

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

intentionally exposed to a pesticide or other chemical. These data, which include studies from 

the Residential Standard Operating Procedures (SOPs)(Turf/Lawn, Indoor Environments, and 
Deltamethrin Human Health Risk Assessment DP No. D413048

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Pets, Impregnated Materials and Treated Paints and Preservative), are (1) subject to ethics review 

pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable 

ethics requirements. For certain studies, the ethics review may have included review by the 

Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, 

can be found at the Agency website. 

2.0 HED Recommendations

HED does not object to the establishment of tolerances for imported freshwater and saltwater 

finfish as specified in Table 2.2.3.

2.1 Data Deficiencies/Conditions of Registration

There are no data deficiencies associated with the proposed tolerance for use of deltamethrin on 

imported finfish. However, HED has identified the need for a turf transferable residue (TTR) 

study to support the existing uses of deltamethrin. This deficiency was not identified in the 2010 

human health assessment scoping document in support of registration review and, therefore, the 

Data Call-In for deltamethrin did not include the required TTR study.

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

TTR values for deltamethrin 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 = 750 

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

deltamethrin may be necessary due to increased use of deltamethrin or advances in EPA risk 

assessments. Therefore, EPA is requiring the 40 CFR TTR data requirement to facilitate any 

necessary exposure assessments refinements and to further EPA’s general understanding of the 

availability of turf transferable pesticide residues.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate methods, utilizing gas chromatography with electron capture detection (GC/ECD), are 

available for enforcing tolerances for residues of deltamethrin in plant commodities, as described 

in Pesticide Analytical Manual (PAM) Volume II, Section 180.422. Another GC/ECD method 

(Method HRAV-22) is available for enforcing tolerances in livestock commodities. Adequate 

confirmatory method validation data have been submitted for these methods, along with 

adequate independent laboratory validation (ILV) trials. 

Multiresidue methods data for cis-deltamethrin and trans-deltamethrin were previously sent to 

FDA. Cis-deltamethrin is completely recovered through Methods 302 and 303, and partially 

recovered through Method 304. Trans-Deltamethrin is partially recovered through Method 303, 

but not recovered through Method 304. 
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2.2.2 International Harmonization

There are currently no established Codex or Canadian maximum residue limits (MRLs) for 

deltamethrin in finfish. There is an MRL in salmon set at 0.03 ppm by the Joint FAO/WHO 

Expert Committee on Food Additives (JECFA), as a veterinary drug (not a pesticide) in 2003. 

As such, harmonization of HED’s recommended tolerance for residues of deltamethrin in 

imported finfish is unnecessary.

2.2.3 Recommended Tolerances

HED has examined the residue chemistry database for deltamethrin. Pending submission of a 

revised Section F (to correct the commodity definitions), there are no human health risk issues 

that would preclude establishing tolerances in freshwater and saltwater finfish. HED 

recommends in favor of establishing tolerances for residues of deltamethrin in finfish, as 

specified in the table below.

Table 2.2.3 Tolerance Summary for Deltamethrin. 

Commodity as Proposed by 

Registrant

Proposed 

Tolerance (ppm)

Recommended 

Tolerance (ppm)

Comments; Correct Commodity 

Definition

Fin fish 0.01 0.01 Fish - freshwater finfish

0.01 Fish - freshwater finfish, farm raised

0.01 Fish - saltwater finfish, other

0.01 Fish - saltwater finfish, tuna

Note to RD: According to HED’s Interim Guidance on Tolerance Expressions (S. Knizner; 27 

May 2009), the tolerance expression for deltamethrin cited in 40 CFR §180.435[a] should be 

revised to state: 

Tolerances are established for residues of deltamethrin, including its metabolites 

and degradates, in or on the commodities listed in the table below. Compliance 

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

deltamethrin [(1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylic 

acid (S)-alpha-cyano-3-phenoxybenzyl ester], and its major metabolites, trans

deltamethrin [(S)-alpha-cyano-m-phenoxybenzyl(1R,3S)-3-(2,2-dibromovinyl)-

2,2-dimethylcyclopropanecarboxylate] and alpha-R-deltamethrin [(R)-alphacyano-m-phenoxybenzyl-(1R,3R)-3-(2,2-dibromovinyl)-2,2-

dimethylcyclopropanecarboxylate] in or on the commodity. 

 

2.2.4 Revisions to Petitioned-For Tolerances

Pharmaq AS requested the establishment of a permanent tolerance, without Section 3 (U.S.) 

registration, for residues of the insecticide deltamethrin in all imported commercially farmed 

finfish at 0.01 ppm. There is, however, no commodity definition covering all finfish. Therefore, 

HED is recommending in favor of establishing tolerances for residues of deltamethrin at 0.01 

ppm in the following four commodities: fish-freshwater finfish; fish-freshwater finfish, farm 

raised; fish-saltwater finfish, other; and fish-saltwater finfish, tuna.
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2.3 Label Recommendations

None. 

3.0 Introduction

3.1 Chemical Identity

Table 3.1 Test Compound Nomenclature.

Compound Chemical Structure

 

Common Name Cis-deltamethrin

Molecular Formula C22H19Br2NO3

Molecular Weight 505.24

Company Experimental Name AEF108569

IUPAC Name (S)-α-cyano-3-phenoxybenzyl (1R,3R)-3-(2,2-dibromovinyl)-2,2-

dimethylcyclopropanecarboxylate

CAS Name (1R,3R)-R-cyano(3-phenoxyphenyl)methyl 3-(2,2-dibromoethenyl)-2,2-

dimethylcyclopropanecarboxylate

CAS Number 52918-63-5

End-use Products (EPs) AlphaMax (No current EPA registration); AMX (No current EPA registration). 

3.2 Physical/Chemical Characteristics

Deltamethrin is a solid under ambient conditions. The compound has a very low solubility in 

water, and low to high solubility in organic solvents. Its octanol/water partition coefficient 

suggests that accumulation of deltamethrin in fatty tissues is possible. See Appendix B for a 

listing of additional physical and chemical properties.

3.3 Pesticide Use Pattern

Pharmaq AS listed the use directions for the AlphaMax/AMX 1% ME formulation of 

deltamethrin in the administrative volume of petition 3E8178. A summary of the proposed use 

pattern is presented in Table 3.3.a, below.

O

O

H

O

Br

Br NC
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Table 3.3.a. Summary of Proposed Directions for Use of Deltamethrin on Finfish. 

Application Timing; Type; 

Equipment1

Use 

Rate

(ppb)

Maximum 

Uses Per 

Season

Max. Seasonal 

Use Rate

(lb ai/A)

PHI2

(Degree 

Days)

Use Directions, 

Application Timing, 

and Limitations

Upon sea lice infestation; bath 

treatment in seawater; closed 

treatment unit (well-boat or seacage enclosed by a tarpaulin).

2 [3] 2 NA3 5

Treatment period of 30 

[40] minutes. Minimum 

RTI4 of 14 days. 

1. In Chile, treatments may also be made in a semi-closed system (skirt); parameters for this treatment method are in 

brackets (i.e., 3 ppb for 40 minutes). 

2. PHI = Pre-Harvest Interval; divide the PHI (5 degree days) by the water temperature (oC) to obtain the number of 

days after treatment that fish must be held before harvest. 

3. NA = Not Applicable. 

4. RTI = Re-Treatment Interval. 

There are no occupational or new proposed residential uses associated with this action for 

establishing a tolerance on imported finfish. However, deltamethrin is registered to control a 

variety of indoor and outdoor pests found on turf, in homes, and in commercial settings, 

including food handling establishments; as well as in pet and paint additive products. For the 

purpose of updating the aggregate human health risk assessment, only previously assessed 

representative residential uses have been re-evaluated using the revised 2012 Residential SOPs.

A more comprehensive assessment might be completed during registration review. A summary 

of the registered uses is provided in Table 3.3.b.

Table 3.3.b. Summary of Registered Residential Uses for Deltamethrin.

Method of 

Application

Product and 

Formulation 

(EPA Reg. No.)

Application 

Rate

Maximum

No.

Applications 

per Season

Maximum 

Seasonal 

Application 

Rate

(lb ai/A)

Use Directions, 

Application Timing, 

Type and Limitations

Aerosol Spray

D-Force 

Insecticide

0.06% ai

(279-9554)

0.00075

lb ai/can

NA

Continues 

killing 

insects up to 

8 weeks

For indoor and outdoor 

use as a spot or crack and 

crevice use. Also apply to 

mattresses, especially 

tufts, folds, and edges for 

control of bed bugs. 

Spray surface until 

slightly wet.

Low pressure 

hand held 

equipment for 

indoor uses and 

hand pressurized 

or power 

operated 

sprayers for 

outdoor use sites

K-Othrine® SC 

Insecticide

4.75% ai

(432-763)

(contains 0.42 lb 

ai/gal)

Indoor use –

0.005 lb ai/gal

Outdoor 

perimeter -

0.214 lb ai/A or

0.005 lb ai/gal

Turf –

0.13 lb ai/A

Ornamentals0.00026

lb ai/gal

NA NA

Indoor applications are to 

be made as spot or crack 

and crevice applications. 

Do not apply as a space 

spray, and do not treat 

entire floor, carpet or 

coverings.

Outdoor applications are 

to be made as building 

perimeter treatments or 

broadcast to lawns, 

recreational grounds and 

ornamentals.
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Table 3.3.b. Summary of Registered Residential Uses for Deltamethrin.

Method of 

Application

Product and 

Formulation 

(EPA Reg. No.)

Application 

Rate

Maximum

No.

Applications 

per Season

Maximum 

Seasonal 

Application 

Rate

(lb ai/A)

Use Directions, 

Application Timing, 

Type and Limitations

Delta Wettable 

Powder 5% ai

(432-832)

0.005 lb ai/gal

NA NA

Indoor applications are to 

be made as spot or crack 

and crevice applications. 

Do not apply as a space 

spray, and do not treat 

entire floor, carpet or 

coverings.

Outdoor applications are 

to be made as broadcast to 

lawns, recreational 

grounds, and ornamentals 

as a general surface spray.

Hose-end 

Sprayer or hand 

held pressurized 

sprayer

RUC-415 

Insecticide

4.75% ai

(432-805)

Lawn –

0.005 lb ai/gal

Perimeter –

0.0023 lb ai/gal

Repeat as 

needed for 

lawns and 

every 7 to 10 

days for 

ornamentals 

if needed.

NA

For use by homeowners 

on lawns, ornamentals, 

decks, foundations, patios,

and other outdoor areas.

Ready-to-Use 

Container, hand 

duster, or 

bulbous duster

Green Light 

Many Purpose 

Dust

0.05% ai

(73327-14)

Crack and 

crevice0.00000025

lb ai/ft2

Home vegetable 

garden –

0.00000066

lb ai/ft2

Repeat at 7-

day intervals 

as necessary.

NA

Apply indoors to crack 

and crevices. Do not 

apply as a broadcast 

application or to 

mattresses. For 

ornamental and home 

garden use, apply thin 

layer of dust on upper and 

lower sides of leaves, 

stems, and flowers

Granular 

Spreader

Delta Granules

0.1% ai

(4-422)

0.000003

lb ai/ft2 or

0.13 lb ai/A

Repeat as 

needed NA

Apply to home lawns, 

under shrubbery, and 

other ornamental 

recreational turf grass 

areas.

Ready-to-Use

Deltamethrin 4% 

Pet Collar for 

Dogs

4 % ai

(68451-1)

0.0024 lb ai/pet

Reapply new 

collar every 

six months

NA

Use only on dogs to 

control fleas and ticks. 

Do not use on puppies 

under 12 weeks old.

Brush, roller or 

conventional 

airless 

equipment

Bug Juice 

Insecticide 

Additive

4.75% ai

(47332-11)

0.42 lb ai/gal

0.005

lb ai/gal/can NA NA

Add 12⁄3 or 81⁄3 fluid 

ounces to either 1 or 5 

gallons of latex coating, 

oil base coating, stains, or 

sealers, then mix well to 

proper dilution. Apply 

product in and on 

residential and non-
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Table 3.3.b. Summary of Registered Residential Uses for Deltamethrin.

Method of 

Application

Product and 

Formulation 

(EPA Reg. No.)

Application 

Rate

Maximum

No.

Applications 

per Season

Maximum 

Seasonal 

Application 

Rate

(lb ai/A)

Use Directions, 

Application Timing, 

Type and Limitations

residential buildings and 

structures including 

residential kitchens and all 

types of food handling 

establishments. Do not 

apply as a broadcast 

interior application.

3.4 Anticipated Exposure Pathways

Humans could be exposed to deltamethrin from consuming food with residues resulting from 

agricultural applications (both pre-harvest and stored grains), and from consuming food treated 

in FHEs. Furthermore, agricultural applications could result in deltamethrin 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. Typically there would be potential for exposure to occupational 

applicators while handling the pesticide prior to application as well as during application. 

However, there is no occupational or residential exposure associated with this tolerance action. 

The potential exposure and risk for homeowners exposed via inhalation during mixing, loading, 

and applying non-restricted end-use products in residential settings, as well as residential postapplication incidental oral exposure for children have been reassessed only for the purpose of 

completing an aggregate risk assessment.

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 

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

post-application are evaluated. 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

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

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

toxicological effects. Type I pyrethroids, which lack an alpha-cyano moiety, induce in rats a 

syndrome consisting of aggressive sparring, altered sensitivity to external stimuli, hyperthermia, 

and fine tremor progressing to whole-body tremor and prostration (T-syndrome). Type II 

pyrethroids, which contain an alpha-cyano moiety, produce in rats a syndrome that includes 

pawing, burrowing, salivation, hypothermia, and coarse tremors leading to choreoathetosis (CSsyndrome) (Verschoyle and Aldridge 1980; Lawrence and Casida 1982). Deltamethrin is a Type 

II pyrethroid. The adverse outcome pathway (AOP, identified using a weight-of-evidence 

approach based on the Bradford-Hill criteria) shared by pyrethroids involves the ability to 

interact with voltage-gated sodium channels (VGSCs) in the central and peripheral nervous 

systems, leading to changes in neuron firing and, ultimately, neurotoxicity (Figure 4.0).

Figure 4.0. Adverse outcome pathway for pyrethroids

4.1 Toxicology Studies Available for Analysis

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

characterization of the hazard profile for children 6 years old and older, as well as for adults. A 

28- or 90-day inhalation study is not available for consideration as required under the Part 158 

toxicology data requirements; however, HED’s HASPOC determined that a subchronic 

inhalation study in the rat is not required for deltamethrin (TXR# 0056944, K. Rury, 4/29/2014). 

In addition, there are ongoing efforts to develop data in juvenile rats (see Section 4.4) to inform 

the potential sensitivity of infants and young children to pyrethroids as a class. Despite the 

missing studies and the ongoing 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. The data from the following studies were used to evaluate the 

hazard potential of deltamethrin:

-Wolansky Acute Oral Study in the Rat

-WIL Laboratory Acute Oral Study in the Rat 

Target 

Tissue 

Dose

VGSC 

Alterations

In Vivo 

Clinical 

Signs

Altered 

Neuronal

Excitability
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-21-Day Dermal Study in the Rat

-90-Day Oral Studies in the Rat and Dog

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

-Developmental Studies in the Rat and Rabbit

-Reproduction Study in the Rat 

-Acute (ACN), Subchronic (SCN), and Developmental Neurotoxicity (DNT) Studies in 

the Rat

-Immunotoxicity Study in the Rat 

-Mutagenicity Battery of Studies

The studies available for consideration of deltamethrin toxicity provide a comprehensive 

database. The Wolansky and WIL studies are acute oral non-guideline studies that measure 

locomotor and functional observational battery (FOB) activity, respectively, and provide robust 

data to evaluate the hazard potential of deltamethrin. In addition, numerous studies from the 

scientific literature conducted over several decades describe the pharmacodynamic and 

pharmacokinetic profile of deltamethrin and 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). 

4.2 Toxicological Profile

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

Deltamethrin targets the nervous system. Neurotoxicity was observed throughout the database,

and effects were seen across species, sexes, exposure duration, and routes of administration. 

Clinical signs characteristic of Type II pyrethroids, such as increased salivation, altered 

mobility/gait, and tremors were seen in experimental toxicology studies including neurotoxicity 

studies (acute and subchronic) in rats, subchronic and chronic studies in dogs and rats, and 

developmental and reproduction studies in rats. In addition to the clinical signs noted above, 

increased sensitivity to external stimuli, abnormal vocalization, and decreased fore- and hindlimb grip strength were commonly observed in the database.

Deltamethrin did not result in any systemic toxicity following dermal exposure for 21 days up to 

the limit dose. There was also no toxicity observed following acute dermal exposure to 

deltamethrin up to a dose of 2000 mg/kg/day. This finding is consistent with the toxicology 

profile of many pyrethroids, including fenpropathrin, zeta-cypermethrin, and allethrin.

Typically, pyrethroids have a low absorption value of ≤ 5% and a high rate of metabolism. 

Deltamethrin had a slightly higher absorption value of 11.3%, although the majority of the 

radioactivity measured was at the skin site (10.6%). This is typical of the pyrethroids, as they are 

lipophilic, and much of the radioactivity measured in the skin of dermal penetration studies with 

pyrethroids is captured in the upper dermal layers and not available for absorption or systemic 

circulation.

Deltamethrin did not have any adverse effects on fetuses or offspring in the prenatal 

developmental studies in rats and rabbits. However, potential qualitative susceptibility was 

observed at high doses in the DNT and 2-generation reproduction study. In the DNT study, an 

increased incidence of vocalization when handled was observed during FOB observations on 
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PND 4 for male pups, and decreased pre- and post-weaning body weight was observed in pups of 

both sexes at 16.1 mg/kg/day. In maternal animals, only decreased body weight and body weight 

gain were observed despite undergoing the same neurological measurements as the pups, 

including FOB analysis. 

In the 2-generation reproduction study, treatment-related effects in the parental animals at the 

high dose (21.2/23.5 mg/kg/day, M/F) were limited to lesions on head, neck, or forelimbs, and 

alopecia in the males and ataxia and hypersensitivity in the females during gestation. In the F1

generation, there were increased pup mortalities (PND 8-14) and clinical findings that were 

observed early in the post-weaning period (i.e., impaired righting reflexes, hyperactivity, splayed 

limbs, vocalization, and excessive salivation) at the high dose (24.9/27.2 mg/kg/day, M/F). 

There was no increase in mortality or clinical signs in the F2 generation. Decreased body weight 

was observed in the adult P and F1 generations, and decreased pup weight was observed in both 

the F1 and F2 pups. It is notable that the dose (24.9/27.2 mg/kg/day) and age of pups (PND 8-14)

where mortality was observed is consistent with the LD50 in PND 11 pups for deltamethrin (11 

mg/kg; Sheets et al. 1994) observed in the literature.

The increased qualitative susceptibility in the DNT and 2-generation reproduction study were 

observed at doses 10- to 20-fold higher than the current points of departure (PODs) selected for 

risk assessment. Therefore, the current PODs are protective of the observed sensitivity.

There was no evidence of immunotoxicity after deltamethrin exposure in the toxicology database 

or in an immunotoxicity study in rats. Deltamethrin is classified as “not likely to be carcinogenic 

to humans.” There was no evidence of carcinogenicity in the combined chronic/carcinogenicity 

study in rats or the carcinogenicity study in mice. In a battery of mutagenicity studies there was 

no evidence of a mutagenic effect.

Deltamethrin has either moderate (Toxicity Category II, MRID 00070734) or minimal (Toxicity 

Category IV, MRID 41651019) toxicity via the oral route of exposure in acute lethality studies 

(LD50) in rats. The acute oral study, which concluded that deltamethrin was of Toxicity 

Category IV, used aqueous methyl cellulose as the vehicle, while another study used both PEG 

200 and sesame oil as the vehicles. It has been reported that deltamethrin is less toxic when 

dissolved in aqueous vehicles such as methyl cellulose, and this might explain the considerable 

difference in results between the two studies (Crofton et al., 1995). Deltamethrin has moderate 

acute toxicity via the inhalation (Toxicity Category II/III) route of exposure and minimal toxicity 

via the dermal (Toxicity Category III) route of exposure. It is minimally irritating to the eye 

(Toxicity Category III) and non-irritating to the skin (Toxicity Category IV). It is not a skin 

sensitizer.

 

4.3 Pyrethroid Pharmacokinetic and Pharmacodynamic Profile

OPP is making best use of the extensive scientific knowledge about the mode of action/adverse 

outcome pathway (MOA/AOP) on pyrethroids in the risk assessments for this class of pesticides. 

In this way, information on a subset of pyrethroids can be used to help interpret and understand 

the toxicological profile for other members of the class. It is notable that a significant portion of 

the scientific literature on pyrethroids utilizes deltamethrin as the test chemical. In the on-going 
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work by the Council for the Advancement of Pyrethroid Human Risk Assessment (CAPHRA), 

deltamethrin is one of two sentinel pyrethroids being used to develop the initial, extensive 

database of in vitro and in vivo toxicology studies and highly refined physiologically-based 

pharmacokinetic (PBPK) models. As such, in the near future, extensive new data will become 

available to further refine the deltamethrin hazard assessment.

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 PK 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 voltage-gated sodium channels (VGSCs) in vital 

tissues and, therefore, do not contribute to overall toxicity.

Age-dependent pharmacokinetic differences have been identified for several pyrethroids (i.e., 

there are differences in the ability of adults and juveniles to metabolize pyrethroids). The 

enzymes that metabolize and detoxify 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 carboxylesterases, plus hepatic carboxylesterases and cytochrome P450s 

(microsomes) is at least 6 times higher for PND 90 rats compared to 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. 

To better understand the role of pharmacokinetics and reduce uncertainty associated with 

extrapolating across species (i.e., rat to human) and life stages, PBPK models, designed to 

predict pyrethroid concentration in tissues following in vivo exposure, have recently been 

developed by the Agency. The Agency has determined that the important PK properties relevant 

for the metabolism and distribution of pyrethroids in the body are sufficiently similar for 

members of this class such that using a ‘generic’ or family model structure for this class is 

scientifically appropriate. In other words, because of the similarities in the PK profiles of 
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pyrethroids, a single model structure is able to predict the tissue dose based on the 

pharmacokinetics of every member of the class. The family modeling approach was primarily 

developed based on PBPK modeling performed with deltamethrin and was presented to and 

supported by the Federal Insecticide, Fungicide, and Rodenticide Scientific Advisory Panel 

(FIFRA SAP), (USEPA 2007).

The initial deltamethrin PBPK model presented to the SAP was developed in the adult male SD 

rat (Mirfazaelian et al. 2006). The deltamethrin PBPK model was further refined based on oral 

bioavailability and disposition studies in rats and included estimates for target tissue 

concentrations in humans (Godin et al. 2010). The initial PBPK model was also extended by 

accounting for age-dependent changes in physiological and biochemical parameters (TorneroVelez et al. 2010) to address juvenile sensitivity in rats. Currently, the CAPHRA, a group of 

pesticide registrants and product formulators, is collecting metabolism and tissue dosimetry data 

from rats and human tissues across different life stages. These data will be used to inform the 

development of PBPK models for additional pyrethroids. The code for the models for the initial 

model is expected to be submitted to the Agency in late 2014 to early 2015. Because of the 

evolving nature of the PBPK model for deltamethrin, the Agency has decided not to use the

existing model for conducting animal to human extrapolation. However, the Agency expects 

that in future risk assessments PBPK modeling will be used to perform interspecies 

extrapolation.

4.3.2 Pharmacodynamics

Pharmacodynamics 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 4.0 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). Choi and Soderlund 

(2006) examined interactions of several pyrethroids, including deltamethrin, with mammalian 

VGSCs expressed in Xenopus (frog) oocytes. Deltamethrin produced modifications of sodium 

channel kinetics consistent with other Type II compounds (Figure 4.3.2). With respect to altered 

neuronal excitability, 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. Cao et al. (2011a) measured sodium influx in 

primary cultures of mammalian (mouse) neurons and demonstrated that deltamethrin caused 

increases in sodium influx in this model. This observation confirms the ability of deltamethrin to 

interact with VGSC in intact mammalian neurons. An additional study by Cao et al. (2011b) 

demonstrated that the interaction of deltamethrin with VGSC caused changes in neuronal 

excitability that resulted in calcium influx into intact mouse neurons. As this effect of 

deltamethrin was entirely blocked by the VGSC blocker tetrodotoxin, it provides evidence that 

the changes in sodium channel function lead to changes in neuronal excitability, as illustrated in 

Figure 4.3.2.
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Figure 4.3.2. Resting modification of rat Nav1.8 sodium channels by deltamethrin expressed in Xenopus oocytes. 

Channel current vs. time traces from individual representative oocytes in the absence or presence (*) of 10 μM 

deltamethrin were obtained during and after 40-ms depolarizations from 100 mV to 10 mV. Calibration bars: 20 ms 

for the x-axis and 500 nAmp on the y-axis. Figure extracted from Figure 3 in Choi and Soderlund (2006).

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 like 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, 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, pharmacodynamic 

(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 

of an adult isoform and a juvenile isoform expressed in frog oocytes to deltamethrin. 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 those in the rat. However, based on the comparable function and 

distribution of sodium channels between the species, the rat is an appropriate surrogate for the 
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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. Following a single oral gavage dose, deltamethrin is 

absorbed quickly in rats. Effects such as tremors, salivation, and impaired mobility were 

observed within 3 hours following oral gavage dosing in the deltamethrin acute neurotoxicity 

study. In addition, effects on motor activity in the Wolansky acute study, FOB observations in 

the WIL acute study, and abnormalities in gait in the chronic dog toxicity study were observed 

within 2, 4, and 5 hours, respectively, following administration of deltamethrin. These 

observations are consistent with the toxicity profiles for other pyrethroids that are marked by 

rapid absorption, metabolism, and elimination, 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). 

The combination of rapid absorption, metabolism, and elimination precludes accumulation and 

increased potency following repeated dosing. Therefore, for most pyrethroids, the acute toxicity 

studies typically result in neurotoxicity at lower doses. In the case of deltamethrin, the chronic 

dog study (NOAEL =1 mg/kg/day) and Wolansky study (BMDL1SD = 1.49 mg/kg) have very 

similar PODs and are the lowest amongst the available studies. The human equivalent doses 

(HED) based on allometric scaling (Table 4.3.3) indicate that the BMDL1SD from the Wolansky 

study is lower than the NOAEL from the chronic dog study. The other two acute studies (WIL 

acute study and the acute neurotoxicity study) have PODs that are approximately 20-30 fold 

higher than the Wolansky acute study (Table 4.3.3). It is notable that both the WIL acute study 

and the acute neurotoxicity study used relatively high vehicle volumes of 5 mL/kg, compared to 

a vehicle volume of 1 mL/kg in the Wolansky acute study, which may account for the 

differences observed. For deltamethrin, the gavage volume can play an important role in potency 

since the volume impacts the absorption characteristics (e.g., timing and amount; Crofton et al, 

1995). In the WIL and acute neurotoxicity studies, it is likely that the relatively high corn oil 

volume caused a reduction in the peak level of deltamethrin in the brain, resulting in lower 

toxicity, thereby increasing the POD.

In general, rat dietary studies tend to have higher NOAELs/LOAELs for pyrethroids because, as 

rats feed continuously, pyrethroids are metabolized and excreted from the system relatively 

quickly, and the overall systemic concentration in the rat remains low. In contrast, bolus/gavage 

dosing results in greater maximal plasma concentrations immediately after dosing. The results 

from the deltamethrin studies are similar in this respect, with the dietary studies having higher 

NOAELs than the bolus/gavage studies. Comparing the PODs established from the Wolansky 

acute study and repeat dosing studies, it is apparent that repeat exposures do not result in lower 

PODs (Table 4.3.3). This observation is consistent with the general kinetic profile for 

pyrethroids. Therefore, the endpoint from the Wolansky acute study is protective of the 

endpoints from the repeat dosing studies and, for the purposes of endpoint selection and 

exposure assessment, only single-day risk assessments need to be conducted.
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Table 4.3.3. Deltamethrin Point of Departure Values versus Treatment Time for Signs of Neurotoxicity

Study Duration Study findings

NOAEL

(mg/kg/day) or 

BMDL

LOAEL 

(mg/kg/day)

or BMD

3⁄4 Body 

Weight 

Adjustment 

for HED 

ComparisonC

Wolansky acute rat (Gavage-1 mL/kg 

corn oil)

Acute, single 

exposure

ABMDL1SD = 1.49 BMD1SD = 

2.48

0.43

WIL acute rat (Gavage-5 mL/kg corn 

oil)

Acute, single 

exposure

BBMDL20 = 10.5 BMD20 = 

14.5

3.05

Acute neurotoxicity rat (Gavage-5 

mL/kg corn oil)

Acute, single 

exposure

15 50 4.36

Developmental Rat (Gavage-1 mL/kg 

corn oil)

10 days 3.3 7 0.96

Subchronic neurotoxicity rat (Dietary) 90 days 14 54 4.07

Sub-chronic rat (Gavage-2.5 mL/kg 

corn oil)

90 days 2.5 10 0.73

Reproductive toxicity (Dietary) 120 days 5.4 21.2 1.57

Chronic dog (Capsule) 1-year 1 10 0.61

Chronic/carcinogenicity rat (Dietary) 2-years 22.2 35.9 6.40

A BMD1SD is the central estimate of the dose that results in decreased motor activity compared to control animals based upon 1 

standard deviation using Benchmark Dose Analysis. BMDL1SD is the 95% lower confidence limit of the central estimate. Data 

and analysis can be found in MRID 47885701.

B BMD20 is the central estimate of the dose that results in a 20% difference in FOB scores compared to control animals using 

Benchmark Dose Analysis. BMDL is the 95% lower confidence limit of the central estimate. Data and analysis can be found in 

MRID 48714301.

C Human Equivalent Doses based on allometric scaling: Scaling Factor 0.75; Default weights: rat = 0.5 kg, dog = 10 kg, Human 

= 70 kg; NOAELH=NOAELD (BWD/BWH)^1-0.75; Sample and Arenal, 1999.

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

There were no indications of fetal toxicity in any of the guideline studies, including 

developmental studies in the rat and rabbit, a developmental neurotoxicity study in rats, and a 2-

generation reproduction study in rats. There was evidence of increased juvenile qualitative 

susceptibility at high doses observed in both the DNT and 2-generation reproduction studies. 

However, these high-dose effects are only at doses 10- to 20-fold higher than the deltamethrin 

POD. The observations of increased qualitative juvenile sensitivity in the guideline studies are 

consistent with the findings of juvenile sensitivity in the literature for deltamethrin, which are 

also high-dose effects.

After reviewing the extensive body of peer-reviewed literature on pyrethroids, the Agency has no 

residual uncertainties regarding age-related sensitivity for women of child bearing age as well as 

for all adult populations and children >6 years of age, based on the absence of pre-natal 

sensitivity observed in 76 guideline studies for 24 pyrethroids and the scientific literature. 

Additionally, no evidence of increased quantitative or qualitative susceptibility was seen in the 

pyrethroid scientific literature related to pharmacodynamics. The Agency is retaining a 3X 

uncertainty factor to protect for exposures of children <6 years of age based on the increased 

quantitative susceptibility seen in studies on pyrethroid pharmacokinetics and the increased 

quantitative juvenile susceptibility observed in high dose studies, such as the deltamethrin 

guideline DNT and 2-generation reproduction studies.
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4.4.1 Completeness of the Toxicology Database

The toxicology database for deltamethrin is largely complete including developmental toxicity 

studies in rats and rabbits, a reproduction study in rats, and acute neurotoxicity (ACN), 

subchronic neurotoxicity (SCN), and developmental neurotoxicity (DNT) studies. HED’s 

HASPOC determined that a subchronic inhalation study in the rat is not required for deltamethrin

(TXR# 0056944). At this time, EPA lacks additional data to address the potential for juvenile 

sensitivity to many pyrethroids, including deltamethrin.

The Agency is expecting additional in vitro and in vivo data. In 2010, the Agency requested 

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

received a single response from the Pyrethrin and Pyrethroids Technical 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, the CAPHRA is 1) conducting in vitro studies demonstrating 

the interaction of pyrethroids with exogenously expressed rat and human VGSCs in Xenopus

oocytes; 2) conducting in vitro studies demonstrating interaction of pyrethroids with VGSCs 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 more data for deltamethrin and other individual pyrethroids become available, the 

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

appropriate. 

For the reasons discussed in Section 4.4, the uncertainty regarding the protectiveness of the 

intraspecies uncertainty factor raised by the literature studies and the absence of the requested 

data warrant application of an additional 3X for risk assessment for infants and children <6 years 

of age.

4.4.2 Evidence of Neurotoxicity

As with other pyrethroids, deltamethrin causes neurotoxicity from interaction with sodium 

channels leading to clinical signs of neurotoxicity. These effects are well characterized and 

adequately assessed by the available guideline and non-guideline studies.

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

High-dose studies in the scientific literature indicate that younger animals are more susceptible 

to the toxicity of pyrethroids. For example, Sheets et al. (1994) found increased brain 

deltamethrin levels in young rats (PND 11 and 21) relative to adult rats (PND 72). These agerelated differences in toxicity are principally due to age-dependent pharmacokinetics. The 

activity of enzymes associated with the metabolism of pyrethroids increase with age (Anand et 

al., 2006). However, in context, normal dietary or residential exposures of juveniles are not 

expected to overwhelm their ability to metabolize pyrethroids. In support, at a dose of 4.0 

mg/kg deltamethrin (near the Wolansky study LOAEL value of 3.0 mg/kg for deltamethrin), the 

change in the acoustic startle response was similar between adult and young rats (Sheets et al, 

1994). In addition, EPA’s Office of Research and Development (ORD) recently developed an 
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age-dependent PBPK model for deltamethrin (Tornero-Velez et al, 2010) that predicts a 3–fold 

increase of pyrethroid in neuronal tissue in younger animals compared to adults. There are 

several studies (in vitro and in vivo) that indicate that PD contributions to pyrethroid toxicity are 

not age-dependent. Examination of specific VGSCs has demonstrated that there is a lack of 

increased sensitivity in either juvenile specific isoforms (Meacham et al., 2008) or in human

isoforms compared to rat variants (Tan and Soderlund, 2009).

There were no indications of fetal toxicity in any of the guideline studies, including 

developmental studies in the rat and rabbit, a developmental neurotoxicity study in rats, and a 2-

generation reproduction study in rats. There was evidence of increased juvenile qualitative 

susceptibility at high doses observed in both the DNT and 2-generation reproduction studies. In 

the DNT study, increased vocalization was observed during FOB handling of pups on PND 4 at 

the same dose where decreased body weight and body weight gain were observed in maternal 

animals (16.1 mg/kg/day). No findings were observed in the maternal animals during FOB 

handling in the DNT. In the 2-generation reproduction study, the P generation showed limited 

clinical signs of neurotoxicity and decreased body weights at the highest dose tested (21.2/23.5 

mg/kg/day, M/F). Effects observed in the F1 generation at the same dose included decreased pup 

weight, increased pup mortality between PND 8-14, increased pup mortality within the first 8 

days post-weaning, and additional clinical signs of neurotoxicity not observed in the parental 

generation. The increased mortality and additional clinical signs were considered to be evidence 

of qualitative sensitivity in juveniles. 

The observations of increased qualitative juvenile sensitivity in the guideline studies are 

consistent with the findings of juvenile sensitivity in the literature for deltamethrin. The 

increased sensitivity in the DNT and 2-generation reproduction study were observed in animals 

of a similar life stage (PND 4 and PND 8-14, respectively) as those in the Sheets study (Sheets et 

al., 1994). Furthermore, the dose at which increased pup death was observed in the 2-generation 

reproduction study (~25 mg/kg/day) is similar to the LD50 value in the Sheets study for pups on 

PND 11 and 21 (11 mg/kg/day). The qualitative sensitivity observed in the DNT and 2-

generation reproduction studies was seen at the highest doses tested. These doses are considered 

to be relatively high (i.e., near the lethal doses) and are ~30- to 50-fold greater than the point of 

departure selected for the acute and chronic dietary reference dose (1.49 mg/kg); therefore, the 

current risk assessment is protective of the observed sensitivity. At doses near the Wolansky 

POD, no effects on parental animals or offspring were observed in either the DNT or 

2-generation reproduction study and, therefore, there is no susceptibility at these doses.

After reviewing the extensive body of peer-reviewed literature on pyrethroids, the Agency has no 

residual uncertainties regarding age-related sensitivity for women of child bearing age as well as 

for all adult populations and children >6 years of age, based on the absence of pre-natal 

sensitivity observed in 76 guideline studies for 24 pyrethroids and the scientific literature. 

Additionally, no evidence of increased quantitative or qualitative susceptibility was seen in the 

pyrethroid scientific literature related to pharmacodynamics. The Agency is retaining a 3X 

uncertainty factor to protect for exposures of children <6 years of age based on the increased 

quantitative susceptibility seen in studies on pyrethroid PK and the increased quantitative 

juvenile susceptibility observed in high doses studies, such as the deltamethrin guideline DNT 

and 2-generation reproduction studies.
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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 high-end health protective residue levels that account for parent and 

metabolites of concern, processing factors, and percent crop treated assumptions. 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 

deltamethrin, 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.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response and Hazard Assessment 

Endpoint selection is discussed in Appendix A.3. Based on the existing and proposed use 

patterns for deltamethrin, the expected exposure profile will be for acute dietary, short-term 

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

conducting dermal (all durations) or intermediate- and long-term inhalation exposure

assessments for adults or children. A chronic dietary risk assessment is not being conducted 

because there is no apparent increase in hazard from repeated/chronic exposures to deltamethrin. 

Therefore, the acute endpoint is protective of the endpoints from repeat dosing studies. A 

chronic dietary exposure assessment is being performed in order to generate background 

exposure estimates to aggregate with residential exposure estimates for the short-term aggregate 

risk assessment.

As previously indicated, the toxicity endpoints in the deltamethrin database are consistently 

based on clinical signs of neurotoxicity. The studies include multiple species, study designs, and 

durations (Table 4.3.3). 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 doseresponse data. In addition to the typical guideline studies, data from two special studies 

(Wolansky study on motor activity and WIL FOB study) evaluating neurobehavioral outcomes 

are available for deltamethrin (Wolansky et. al. 2006; Weiner et. al. 2009). Wolansky et al.

measured motor activity at the time of peak effect after exposure to 11 pyrethroids, including 

deltamethrin, although other neurobehavioral parameters were not assessed. Dose-response 

relationships were determined using 6-11 doses per pyrethroid (6 doses used for deltamethrin) 

and 8-18 rats per dose group, minimizing variability and increasing the confidence in the BMD 

estimates determined from this study. Moreover, each pyrethroid was evaluated by the same 

scientist, thus decreasing some of the variability associated with neurobehavioral measures. In 

the WIL study, 17 pyrethroids including deltamethrin were evaluated using a specially designed 
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FOB study focused on the outcomes associated with pyrethroid toxicity syndromes at the time to 

peak effect. Dose-response relationships were determined using 2-3 doses per pyrethroid (3 

doses used for deltamethrin) and 10 male rats per dose group. 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 deltamethrin, thereby increasing the POD.

Observations of salivation, effects on mobility/gait, and tremors were the most prominent 

findings in the guideline experimental toxicology studies and were considered in the POD 

determination. Given the multiple strengths associated with the study design of Wolansky, et al. 

(2006) and the resulting well-defined dose-response curve, the Wolansky study provides the 

most robust data set for extrapolating risk from deltamethrin. Although the guideline studies 

typically have only three treatment groups, they often do not evaluate clinical signs at the time of 

peak effect, and the scoring metrics for neurotoxicity parameters vary widely among guideline 

studies, the NOAELs/LOAELs from the guideline studies, in general, are consistent with, and 

support, the findings of the Wolansky study. 

A BMD analysis was conducted by the Agency for all the pyrethroids included in the Wolansky 

study (MRID 47885701). Overall, because of the large number of doses and high quality 

measurements, the BMD analysis yielded high-confidence results. In performing BMD analysis, 

a benchmark response (BMR) must be selected. As a general approach, it is preferable to use a 

combination of biological and statistical factors in the BMR selection. In the case of motor 

activity data, the scientific community has not established a specific level of change that would 

be considered to be adverse. Therefore, OPP has elected to use one standard deviation (1SD) 

from the control group, as suggested, for continuous endpoints in the Agency’s BMD guidance 

(USEPA 2012) as the BMR. OPP has estimated both the BMD1SD and the BMDL1SD (where the 

BMDL1SD is the lower 95% confidence limit of the BMD1SD). The BMD1SD and the BMDL1SD

for deltamethrin are 2.48 mg/kg and 1.49 mg/kg, respectively. As a matter of science policy, 

EPA uses the BMDL, not the BMD, for deriving PODs. Therefore, the BMDL1SD of 1.49 mg/kg 

is being used as the dose for risk assessment. 

As described in section 4.3.1, there are PBPK models currently available for species 

extrapolation from rats to humans. For the current action, the use of PBPK models to predict 

human equivalent concentrations is not necessary to establish a tolerance on finfish. 

Acute Dietary (All Age Groups): Quantitation of the dietary risks was performed using the acute 

oral Wolansky study, with a BMDL1SD value of 1.49 mg/kg and a BMD1SD value of 2.48 mg/kg 

based on decreased locomotor activity. The acute neurotoxicity, chronic dog, and WIL acute 

studies were all considered for risk assessment because they all had effects that were observed 

within hours of dosing. However, the Wolansky study had the lowest POD among all studies 

and is considered the most robust study in the database. The chronic dog study had a slightly 

lower NOAEL (1 mg/kg/day); however, the human equivalent dose based on allometric scaling 

was actually higher for the chronic dog study (0.61 mg/kg/day) compared to the Wolansky study 

(0.43 mg/kg) (Table 4.3.3). As there is no apparent increase in hazard from repeated/chronic 

exposures to deltamethrin, the acute dietary exposure assessment is protective of chronic dietary 

exposures. Accordingly, a chronic dietary assessment was not conducted.
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Incidental oral short-term: Quantitation of the incidental oral risks was performed using the 

acute oral Wolansky study, with a BMDL1SD value of 1.49 mg/kg and a BMD1SD value of 2.48

mg/kg based on decreased locomotor activity. The BMDL1SD value of 1.49 mg/kg is protective 

of potential offspring effects observed in the DNT and 2-generation reproduction study.

Short-term Dermal: A 21-day dermal study in rat for deltamethrin is available for consideration. 

However, no treatment-related findings were observed at the limit dose. There was also no 

toxicity observed following acute dermal exposure to deltamethrin up to a dose of 2000 mg/kg. 

Therefore, a dermal hazard was not identified for deltamethrin, and no dermal risk assessment 

will be conducted. This finding is consistent with the toxicology profile of many pyrethroids. 

No dermal hazard has been identified for fenpropathrin, zeta-cypermethrin, or allethrin. 

Typically, pyrethroids have a low dermal absorption value of ≤ 5% and a high rate of 

metabolism. Deltamethrin had a slightly higher dermal absorption value of 11.3%, although the 

majority of the radioactivity measured was at the skin site (10.6%). This is typical of the 

pyrethroids, as they are lipophilic, and much of the radioactivity measured in the skin of dermal 

penetration studies with pyrethroids is captured in the upper dermal layers and not available for 

absorption or systemic circulation. 

Short-term Inhalation: A route-specific inhalation study is not available for deltamethrin;

however, HASPOC waived the requirement for this study (TXR# 0056944). As a result, the oral 

BMDL1SD of 1.49 mg/kg from the Wolansky acute rat study is being used for this endpoint to 

extrapolate inhalation risk because of the overall robust nature of the study and the lack of 

increased hazard from repeated/chronic exposures to deltamethrin. Absorption and toxicity via 

the inhalation route are assumed to be equal to toxicity via the oral route. 

4.5.2 Recommendation for Combining Routes of Exposure for Risk Assessment

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

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

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

effects. For deltamethrin, there are no routes to combine despite all exposure scenarios being 

based on the same endpoint: decreased motor activity. No dermal hazard was identified for 

deltamethrin, and the inhalation route of exposure only applies to occupational and residential

handlers. Furthermore, inhalation post-application exposure is expected to be minimal. 

Therefore, incidental oral is the only potential route of exposure for children. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

There was no evidence of carcinogenicity in either the rat or mouse long-term dietary studies up 

to the highest dose tested, nor was there any mutagenic activity in bacteria or cultured 

mammalian cells. Deltamethrin is classified as “not likely to be carcinogenic to humans” in 

accordance with the EPA Final Guidance for Carcinogen Risk Assessment (3/29/2005).
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4.5.4 Summary of Points of Departure and Toxicity Endpoints

Table 4.5.4.1 Summary of Deltamethrin Toxicological Doses and Endpoints for Use in Dietary and NonOccupational Human Health Risk Assessment

Exposure 

Scenario

Point of 

Departure

Uncertainty/FQPA 

Safety Factors 

RfD, PAD, Level of 

Concern for Risk 

Assessment

Study and 

Toxicological Effects

Acute 

Dietary-

(≥ 6 years 

old)

Wolansky 

BMDL1SD = 1.49

mg/kg

UFA = 10X

UFH = 10X

FQPA SF = 1X

Acute RfD = 0.015

mg/kg

aPAD =0.015 

mg/kg/day

Wolansky BMD1SD = 

2.48 mg/kg

based on decreased 

motor activity

Acute 

Dietary-

(< 6 years 

old)

Wolansky 

BMDL1SD = 1.49

mg/kg

UFA = 10X

UFH = 10X

FQPA SF = 3X

Acute RfD = 0.015 

mg/kg

aPAD =0.005

mg/kg/day

Wolansky BMD1SD = 

2.48 mg/kg

based on decreased 

motor activity

Incidental 

Oral (Shortterm)

Wolansky 

BMDL1SD = 1.49

mg/kg

UFA = 10X

UFH = 10X

FQPA SF = 3X

Residential LOC for 

MOE = 300

Wolansky BMD1SD = 

2.48 mg/kg

based on decreased 

motor activity

Dermal 

(short-term; 

all 

populations)

A dermal assessment was not conducted based on the lack of effects in a 21-day dermal study 

and low potential for dermal absorption for deltamethrin.

*Inhalation 

(Short-term; 

≥ 6 years old)

Wolansky 

BMDL1SD = 1.49

mg/kg

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential LOC for 

MOE = 100

Wolansky BMD1SD = 

2.48 mg/kg

based on decreased 

motor activity

*Inhalation 

(Short-term; 

< 6 years old)

Wolansky 

BMDL1SD = 1.49

mg/kg

UFA = 10X

UFH = 10X

FQPA SF = 3X

Residential LOC for 

MOE = 300

Wolansky BMD1SD = 

2.48 mg/kg

based on decreased 

motor activity

Cancer (oral, 

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of treatment 

related tumors in two adequate rodent carcinogenicity studies.

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. * Inhalation absorption is assumed to be equivalent 

to oral absorption.

5.0 Dietary Exposure and Risk Assessment 

5.1 Metabolite/Degradate Residue Profile
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5.1.1 Summary of Plant and Animal Metabolism Studies

Based on acceptable metabolism data in plants and animals, HED has concluded that the nature 

of the residue in plants and animals is adequately understood. In both plants and animals, the 

residues of concern for both tolerance enforcement and risk assessment are the cis-, trans- and 

alpha-R- isomers of deltamethrin.

In acceptable tomato, cotton, apple, and corn metabolism studies, the three deltamethrin isomers 

(cis-, trans-, and alpha-R-) were the major [14C]-residues. All other metabolites were present at 

<10% of the total radioactive residue (TRR), or accounted for <0.01 ppm. In plants, the main 

component of the active ingredient, cis-deltamethrin, undergoes isomerization to form trans- and 

alpha-R-deltamethrin. Each of these isomers can also undergo cleavage at the ester linkage to 

yield 3-phenoxybenzaldehyde, and cis- or trans-Br2CA metabolites that can be further oxidized, 

reduced, and/or conjugated. Deltamethrin is also directly hydroxylated to 4’-

hydroxydeltamethrin, or the nitrile group can be hydrolyzed to form an amide metabolite. 

Acceptable cattle and poultry metabolism studies were conducted using [14C]-tralomethrin, a 

closely related pyrethroid that breaks down into deltamethrin via debromination. In these 

studies, deltamethrin was the major residue in cattle fat, muscle, and milk (48-96% TRR), and 

was detected in kidneys at 1-2% of the TRR. In the poultry metabolism studies, deltamethrin 

was also the major residue identified in fat, muscle, and egg yolks (32-85% TRR), and was 

detected in liver at 14% of the TRR. In both the cattle and poultry studies, deltamethrin was 

further metabolized by cleavage at the ester linkage to yield 3-phenoxybenzaldehyde and Br2CA 

metabolites, which were further oxidized, reduced, and/or conjugated. Free and conjugated 

residues of Br2CA and 3-phenoxybenzaldehyde were major components detected in liver, 

kidney, and muscle of both cattle and poultry. In poultry, minor amounts of 4’-

hydroxydeltamethrin were also detected in liver.

5.1.2 Summary of Environmental Degradation

When applied to the field, deltamethrin is likely to partition into the soil and organic matter in the 

crops. It appears to bind strongly to soil and organic matter, though binding is not instantaneous 

(KOC >>100,000, immobile). It is not expected to leach into sub-surfaces. It might reach aquatic 

environments via spray drift or in runoff events accompanied by erosion. Deltamethrin appears to 

be moderately to highly persistent in terrestrial environments. It has the potential to persist in 

aquatic environments, where it might partition with the sediment. Because of its low Henry’s Law 

Constant, deltamethrin is unlikely to volatilize substantially. 

Deltamethrin is relatively stable at pH 5 and 7. However, it rapidly degrades (half-life of 2.5 days) 

at an alkaline pH of 9 to form Br2CA and 3-phenoxybenzaldehyde. It does not appear to 

photodegrade substantially in aqueous solutions. 

Based on acceptable aerobic soil metabolism data, deltamethrin degrades rapidly (half-life 11-19 

days) to form DBVA or Br2CA (<10%) and CO2. The proposed routes of degradation are ester 

hydrolysis and microbial-mediated mineralization to CO2. In an anaerobic soil metabolism study, 

deltamethrin degraded in an Arizona sandy loam (pH 8.1) with a half-life of 32-36 days for the 
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benzyl and geminal labels, respectively. For the geminal label experiment, only 1 metabolite, 

Br2CA or decamethrinic acid, was found at 49% of the applied radioactivity by Day 30, and 

remained at about this level on Days 59 (52%) and 90 (48%). For the benzyl label, the only 

metabolite identified was 3-phenoxybenzoic acid, which was only detected in a Day-30 sample, 

accounting for only 3% of the applied radioactivity. In an aerobic aquatic metabolism study, 

consisting of loam or sandy loam test systems from the Netherlands, the half-lives for the whole 

systems were 26 and 120 days, respectively. The major transformation product was the alpha-Risomer of deltamethrin, at up to 24% in the sandy loam. 

In a fish bioconcentration study, deltamethrin had bio-concentration factors of 189x and 3630x in 

edible and visceral fish tissues, respectively. The whole body BCF of 698x was calculated from 

edible and visceral fish tissue results. The majority of the radioactive residue found in fish was 

parent, accounting for 78 and 83% of the TRR in edible and visceral fish tissues, respectively.

 

5.1.3 Comparison of Metabolic Pathways

In the rat metabolism studies, deltamethrin was relatively well absorbed after oral dosing, with 

rapid excretion via the urine and feces. Fecal extracts contained mostly unabsorbed, unchanged 

deltamethrin. Absorbed deltamethrin was cleaved at the ester site, and the cleaved products were 

rapidly conjugated into 4’SO4-m-phenoxybenzoic acid and dibromocyclopropanecarboxylic 

acid-glucuronide, and then excreted in the urine.

In plants and animals, parent cis-deltamethrin can form the trans and alpha-R isomers, which 

can then undergo hydrolysis at the ester linkage. 

5.1.4 Residues of Concern Summary and Rationale

The residues of concern in plants and livestock for both risk assessment and tolerance 

enforcement are cis-, trans-, and alpha-R deltamethrin. These same three isomers are the 

residues of concern for risk assessment in drinking water.

TABLE 4.1.1 Summary of Deltamethrin Metabolites and Degradates to be Included in Risk Assessment 

and the Tolerance Expression.

Matrix Residues in Risk Assessment Residues in the Tolerance Expression

Plants Primary crops Cis-, trans- and alpha-R-deltamethrin Cis-, trans- and alpha-R-deltamethrin

Rotational crops Not Applicable Not Applicable

Livestock Ruminants Cis-, trans- and alpha-R-deltamethrin Cis-, trans- and alpha-R-deltamethrin

Poultry

Drinking water Cis-, trans- and alpha-R-deltamethrin Not Applicable

5.2 Food Residue Profile

Pharmaq AS submitted the results of a total of six deltamethrin magnitude of the residue studies 

on finfish. The studies examined the magnitude of residue in Atlantic salmon and rainbow trout 

following bath treatment in seawater. Residues were below the LOQ in all samples in all six 

studies. 
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In the first set of residue studies, the fish were treated one time in tanks containing 3 ppb 

deltamethrin for 40 minutes at either 5°C or 10°C. Residues of deltamethrin were below the 

limit of quantitation (LOQ) of 0.01 ppm in all samples of salmon muscle with skin, and salmon 

liver. 

In the second set of studies, deltamethrin residues were measured in large Atlantic salmon and 

rainbow trout after bath treatment in seawater. The fish were treated one time in tanks 

containing deltamethrin at 3 ppb in seawater for 40 minutes at 5°C. Residues of deltamethrin 

were below the LOD (<0.005 ppm) in all samples of salmon muscle with skin collected 1, 2, and 

6 hours after exposure, and in all samples of rainbow trout muscle with skin collected 2 and 6 

hours after exposure. In samples of rainbow trout muscle with skin collected 1 hour after 

exposure, quantifiable residues were observed in one sample at 0.0056 ppm. Residues were 

below the LOD of 0.005 ppm in all remaining samples. 

The third set of studies investigated the magnitude of deltamethrin residues in large commercial 

Atlantic salmon and rainbow trout following bath treatment in seawater. In both studies, the fish 

were treated one time in tanks containing 2 ppb deltamethrin for 30 minutes at ≤12°C. Residues 

of deltamethrin were below the LOQ (<0.005 ppm) in all samples of salmon muscle with skin, 

and in all samples of rainbow trout muscle with skin.

The residue data are presented in Table 5.2.1. 

Table 5.2.1. Summary of Residue Data from Fish Treatment Study with Deltamethrin

Matrix Exposure 

Level

Time Point

(Hours)1

Residue Levels (ppm)2

n Min. Max. Median Mean Std. Dev.

Muscle with 

skin

3 ppb 2 10 <0.01 <0.01 0.01 0.01 NA

6 20 <0.01 <0.01 0.01 0.01 NA

24 20 <0.01 <0.01 0.01 0.01 NA

Liver 2 10 <0.01 <0.01 0.01 0.01 NA

6 20 <0.01 <0.01 0.01 0.01 NA

24 20 <0.01 <0.01 0.01 0.01 NA

1. Time after termination of bath exposure to deltamethrin in seawater for 40 minutes at 10 or 5°C. 

2. For calculation of median, mean, and standard deviation, the LOQ (0.01 ppm) was used for any results reported as 

<LOQ (n = number of samples; NA = Not Applicable). 

There are currently no established Codex or Canadian maximum residue limits (MRLs) for 

deltamethrin in finfish. There is an MRL in salmon set at 0.03 ppm by the Joint FAO/WHO 

Expert Committee on Food Additives (JECFA), as a veterinary drug (not a pesticide) in 2003. 

As such, harmonization of HED’s recommended tolerance for residues of deltamethrin in 

imported finfish is unnecessary.

The registrant has not submitted processing studies for finfish, and none are needed.

5.3 Water Residue Profile

EFED provided the results of a drinking water assessment that was performed for deltamethrin 

(D335136, J. Melendez, 4/24/2007). EFED calculated the estimated drinking water 
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concentrations (EDWCs) for deltamethrin based on a maximum application rate of 0.45 lb 

a.i./A/season. The acute drinking water concentration in surface water is 0.20 ppb, based on 

application to sweet corn. The cancer/chronic EDWC is 0.0771 ppb (based on application to 

sweet corn with the highest application rate). The Screening Concentration in Groundwater 

(SCIGROW) Model for groundwater generated an EDWC of 0.200 ppb. This value is the same 

as the surface water value and was recommended for use both for acute and chronic exposures. 

Both the acute surface drinking water concentration and the ground drinking water concentration 

were limited by the solubility of deltamethrin.

5.4 Dietary Risk Assessment

Acute and chronic dietary (food and drinking water) exposure 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 dietary exposure assessment is partially refined. It is based on tolerance level residues 

for most commodities and Pesticide Data Program (PDP) monitoring data for cereal grains, 

apples, apple juice, apple sauce, cantaloupe, carrots, pears, tomatoes, watermelons, cucumbers, 

soybeans, and milk. Modeled EDWCs from EFED were used for drinking water. The 

assessment is also based on the maximum percent crop treated estimates provided by the 

Biological and Economic Analysis Division (BEAD). DEEM-FCID Version 7.81 default 

processing factors were used for some processed commodities and empirical factors were used 

for others.

Chronic Assessment

Deltamethrin is registered for use in food handling establishments (FHEs). As a result, residue 

values were entered for all commodities in DEEM-FCID. For most commodities with 

established and proposed tolerances, the tolerance was used as the residue value. For cereal 

grain commodities, average monitoring data values were used. For milk, PDP monitoring data 

were used. For the commodities for which the only established tolerance is the FHE tolerance, a 

residue value of 0.025 ppm (1⁄2 the FHE tolerance) was used. For commodities with tolerances 

for agricultural uses, BEAD’s average percent crop treated estimates were generally used. 

BEAD provided an estimate of the probability that a food a person consumes contains residues 

as a result of treatment in an FHE at some point with any pesticide. It is not specific to 

deltamethrin. This estimate is 4.65%. In the chronic assessment, this value was used for the 

same commodities as the ones with the FHE residue value (0.025 ppm). As with the acute 

assessment, modeled EDWCs were used for drinking water.
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Cancer Assessment

Cancer risk is not of concern for deltamethrin because the compound is classified as “not likely 

to be carcinogenic to humans.” 

5.4.2 Percent Crop Treated Used in Dietary Assessment

Acute Assessment

The following maximum percent crop treated estimates (SLUA, 5/5/2014, BEAD Usage and 

Label Use Team) were used in the acute dietary risk assessment for the following crops that are 

currently registered for deltamethrin:

Crops with an assumption of 2.5% CT: apples, cantaloupes, carrots, soybeans, tomatoes, and

watermelons.

Crops with an assumption of 5% CT: cucumbers and pears.

Chronic Assessment

The following average percent crop treated estimates were used in the chronic dietary risk 

assessment for the following crops that are currently registered for deltamethrin: 

Crops with an assumption of 1% CT: apples, cantaloupes, carrots, cotton, potatoes (some food 

forms), pumpkins, radishes, squash, tomatoes, turnips, and watermelons.

Crops with an assumption of 2.5% CT: cucumbers, leeks, onions, pears, and sunflowers.

Crops with an assumption of 4.65% CT: almonds, pistachios, potatoes (some food forms), 

soybeans, sweet corn, and walnuts.

Crops with an assumption of 5% CT: canola and peppers. 

Finally, BEAD estimated 40% CT for globe artichokes.

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 deltamethrin). In the chronic assessment, for the commodities for which 1⁄2 the FHE tolerance 

was used, the assumption was made that there was a 4.65% chance that a food item consumed by 

a person contained deltamethrin residues as a result of treatment at some point in an FHE.

5.4.3 Acute Dietary Risk Assessment

The acute dietary 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 dietary risk estimate for the 
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general U.S. population is 17% of the aPAD. The population subgroup with the highest acute 

dietary risk estimate is Children 3-5 years old, which uses 80% of the aPAD. As percent crop 

treated estimates were used for some commodities, the risk estimates are being reported at the 

99.9th percentile of exposure.

5.4.4 Chronic Dietary Exposure Assessment

The chronic dietary exposure estimate for the general U.S. population is 0.000254 mg/kg/day. 

The population subgroup with the highest chronic dietary exposure estimate is Children 1-2

years old, which has a dietary exposure estimate of 0.000822 mg/kg/day.

5.4.5 Summary Table

Table 5.4.5. Summary of the Acute Exposure and Risk Estimates for Deltamethrin

Population 

Subgroup

Acute Assessment (99.9th Percentile) Chronic Assessment

aPAD, 

mg/kg/day

Exposure Estimate, 

mg/kg/day

% aPAD

cPAD

Exposure 

Estimate, 

mg/kg/day

% cPAD

U.S. Population 0.0149 0.002588 17 NA 0.000254

NA

All infants 0.005 0.003359 67 NA 0.000298

Children 1-2 yrs* 0.005 0.003797 76 NA 0.000822

Children 3-5 yrs* 0.005 0.003989 80 NA 0.000601

Children 6-12 yrs 0.0149 0.002346 16 NA 0.000378

Youth 13-19 yrs 0.0149 0.001682 11 NA 0.000207

Adults 20-49 yrs 0.0149 0.002211 15 NA 0.000194

Adults 50-99 yrs 0.0149 0.001709 11 NA 0.000210

Females 13-49 yrs 0.0149 0.002672 18 NA 0.000192

*Most highly exposed population subgroups

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

(M.Collantes, D418867, 6/11/2014)

This document provides a revised residential handler and post-application exposure assessment 

for existing residential indoor, outdoor, pet, and paint preservative uses that were evaluated in 

the 2004 ORE assessment (M. Collantes, D307927, Oct. 14, 2004). The revised assessments 

reflect updates to HED’s 2012 Residential SOPs, along with policy changes for body weight 

assumptions, updated inhalation and incidental oral toxicological endpoints and doses, and 

reduced FQPA Safety Factors for adult and children’s populations. The revised residential 

exposure estimates have been provided for the purpose of updating the aggregate human health 

risk assessment.

6.1 Residential Handler Exposure/Risk Estimates for Registered Uses

As the deltamethrin labels do not identify these residential use products as a restricted use, a 

revised residential handler exposure assessment was performed to be protective of potential 

homeowners who apply deltamethrin as indoor, outdoor, turf, paint, and pet collar use/treatment. 
Deltamethrin Human Health Risk Assessment DP No. D413048

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The quantitative exposure/risk assessment developed for the previously assessed residential 

handlers is based on the following (worst case) scenarios: 

 Mix/Load/Apply liquid sprays using manually pressurized handwand for indoor spot and 

crack & crevice treatment, 

 Mix/Load/Apply liquid suspension concentrate (SC) sprays using hose-end sprayer for 

turf/lawn,

 Mix/Load/Apply liquid (SC) sprays using backpack sprayer for turf/lawn,

 Mix/Load/Apply wettable powder using manually pressurized handwand for turf/lawn,

 Mix/Load/Apply wettable powder using backpack sprayer for turf/lawn,

 Mix/Load/Apply paint additive using airless sprayer,

 Load/Apply granules using belly grinder to lawn/turf,

 Load/Apply granules using shaker can to outdoor sites,

 Apply aerosol spray to outdoor and indoor areas as a spot and crack & crevice treatment,

 Apply insecticidal dust to outdoor crack and crevice sites using shaker can, and

 Apply pet collar to dogs.

Summary of Residential Handler Exposure and Risk Estimates

Representative registered residential uses were reassessed using the revised 2012 Residential 

SOPs and revised inhalation endpoints and doses. All residential handler scenarios resulted in 

inhalation risk estimates greater than the LOC (MOEs ≥ 100) and are not of concern. The 

exposure estimates are summarized for the worst-case residential handler exposure scenario for 

each registered product in Table 6.1.

Table 6.1. Residential Handler Exposure and Risk Estimates for Deltamethrin Registered Uses.

Exposure Scenario Level of 

Concern

Inhalation 

Unit 

Exposure

(mg/lb ai)

Maximum 

Application 

Rate1

Area Treated or 

Amount 

Handled Daily2

Inhalation

Dose 

(mg/kg/day)3 MOE4

Mix/Load/Apply

Manually Pressurized 

Handwand for Indoor 

Crack & Crevice and 

Mattress Treatment 

K-Othrine SC 

Insecticide (4.75% ai)

Reg. No.432-763

100

1.1 0.005 lb ai/gal 0.5 gals 0.000034 43,000

Hose-end Sprayer –

Turf

K-Othrine SC 

Insecticide (4.75% ai)

Reg. No.432-763

0.022 0.13 lb ai /A 0.5 A 0.000018 83,000

Back Pack- Garden and 

Trees 

K-Othrine SC 

Insecticide (4.75% ai)

Reg. No.432-763

0.14 0.005 lb ai/gal 5 gals 0.000044 34,000
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Table 6.1. Residential Handler Exposure and Risk Estimates for Deltamethrin Registered Uses.

Exposure Scenario Level of 

Concern

Inhalation 

Unit 

Exposure

(mg/lb ai)

Maximum 

Application 

Rate1

Area Treated or 

Amount 

Handled Daily2

Inhalation

Dose 

(mg/kg/day)3 MOE4

Manually Pressurized 

Handwand and 

Backpack – Lawn/Turf 

and Gardens/Trees

Delta Wettable Powder

(5% ai)

Reg. No. 432-832

1.1 0.005 lb ai/gal 5 gals 0.00034 4,300

Airless Sprayer

Bug Juice Insecticidal 

Additive (4.75% ai)

Reg. No. 47332-11

0.56

0.005

lb ai/gal/can 5 gals 0.00018 8,500

Load/Apply

Belly Grinder

Delta Granules

(0.1% ai)

Reg. No. 4-422

100 0.039

0.000003

lb ai/ft2

1200 ft2 0.0000018 850,000

Apply

Shaker Can –

Garden/Trees

Many Purpose Dust

RTU (0.05% ai)

Reg. No. 73327-14

100

18

0.00000066

lb ai/ft2

1200 ft2

0.00018 8,400

Aerosol Spray –

Garden/Trees

D-Force Insecticide

(0.06% ai)

Reg. No. 279-9554

3

0.00075

lb ai/can

2 cans 0.000056 26,000

Aerosol Spray –

Indoor Crack & Crevice 

and Mattress

D-Force Insecticide

(0.06% ai)

Reg. No. 279-9554

0.5 can 0.000014 110,000

Ready-to-Use Pet Collar

(4% ai)

Reg. No. 4-422

negligible 0.0024 lb ai/pet 2 pet NA

1 Based on registered or proposed labels.

2 Based on HED’s 2012 Residential SOPs

3 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate × Area Treated or Amount Handled ÷ Body Weight

(80 kg).

4 Inhalation MOE = Inhalation NOAEL (1.49 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).
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6.2 Residential Post-application Exposure/Risk Estimates for Registered Uses

There is the potential for post-application exposure for individuals resulting from being in an 

environment that has been previously treated with deltamethrin. A residential post-application 

exposure assessment and amendment were previously performed for existing residential indoor, 

outdoor, lawn, pet collar, and paint uses in 2003 and 2004 (D287835, M. Collantes, 7/18/2003; 

and D307927, M. Collantes, 10/14/2004). Risk estimates for these registered residential 

scenarios have been revised to reflect updates to HED’s 2012 Residential SOPs along with 

policy changes for body weight assumptions and updated toxicological endpoints. The 

quantitative exposure assessment for residential post-application exposures is based on the 

following scenarios: 

 Incidental oral (hand-to-mouth and object-to-mouth) contact with residues deposited on 

lawn/turf resulting from liquid and granular formulations,

 Incidental oral (soil ingestion) contact with residues deposited on lawn/turf resulting from

liquid and granular formulations,

 Episodic granular ingestion resulting from granular formulations,

 Incidental oral (hand-to-mouth and object-to-mouth) contact with residues deposited on 

indoor surfaces from spot and crack & crevice treatments resulting from liquid formulations,

 Inhalation exposure of residues resulting from exposure to indoor pesticide vapors from 

liquid formulations, and

 Incidental oral (hand-to-mouth) contact with residues from dogs wearing treated pet collars.

Residential Post-application Exposure Data and Assumptions:

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

post-application risk assessment and are briefly described below. Each assumption and factor is 

detailed in the 2012 Residential SOPs and a chemical specific dislodgeable residue study 

performed on dogs wearing impregnated pet collars (Deltamethrin: Two month dislodgeable 

residue study of deltamethrin in beagle dogs treated with Scalibor® Protector Band; MRID# 

49350101; D420043; March 2014; A. Prohaczik, D.M.V. Ph.D.; MSD Animal Health Innovation 

SAS, Beaucouze France). This residue transfer study was recently submitted in support of the 

registered pet collar use. It was determined to be acceptable for risk quantitation. A summary of 

this study is provided in the 2014 occupational and residential exposure assessment for 

deltamethrin (D418867, M. Collantes, 6/11/2014).

Episodic Granular Ingestion

The product, Delta Granules (Reg. No. 4-422) may be applied by a spreader to home lawns, 

under shrubbery, and to other ornamental recreational turf grass areas. The Residential SOP for 

Turf and Lawns was used to estimate post-application doses from incidental ingestion of 

pesticide granules applied to lawns and gardens. Ingestion of granules is considered an episodic 

(or acute) event and not a routine behavior for children. Since HED does not believe that this 

would occur on a regular basis, the scenario is considered to be an acute poisoning rather than a 

short-term exposure typically assessed in HED’s human health risk assessments. Furthermore, 
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the registered label instructs the user to thoroughly water treated areas after application so that 

both granules and lawns are moistened to ensure granules dissolve properly. 

In an effort to refine the post-application dose and respective MOE for incidental ingestion of 

granules, the default granular ingestion rate of 0.3 g/day was adjusted to 0.14 g/day to reflect the 

amount of product applied on a per area basis (3 lb/1000 ft2). This adjustment resulted in a dose 

of 0.14 mg/kg/day and an MOE of 120. In order to achieve an MOE greater than the LOC 

(MOE ≥ 300), the application rate would need to be reduced from 0.000003 lb ai/ft2to 0.000001 

lb ai/ft2, which would result in a post-application dose of 0.005 and an MOE of 300.

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

In the absence of toxicity via the dermal route, no quantitative dermal post-application exposure 

assessment was required. All the representative indoor/outdoor and pet incidental oral (hand-tomouth, object-to-mouth, soil ingestion, and episodic granule ingestion) post-application 

scenarios resulted in risk estimates ranging from an MOE of 630 to 24,000 and are not of 

concern. A summary of the registered residential post-application exposure and risk estimates 

for deltamethrin is provided in Table 6.2.

Table 6.2. Registered Residential Post-application Non-cancer Exposure and 

Risk Estimates for Deltamethrin.

Lifestage

Post-application Exposure 

Scenario Application 

Rate1

Dose 

(mg/kg/day)2 MOEs3 Combined MOEs

Use Site Route of 

Exposure

Adult Indoor C&C

K-Othrine SC 

Insecticide

Reg. No.432-

763

(0.06% ai)

Dermal

0.005

lb ai/gal

NA NA

NA

Inhalation

Child

Dermal NA NA Inhalation

HTM 0.0000614 24,000

OTM 0.000039 38,000

Adult Indoor C&C 

and Mattress

D-Force 

Ready-to-Use 

Aerosol Spray 

Reg. No. 279-

9554

Dermal

0.00075 lb 

ai/can

Dermal Mattress NA NA

Inhalation

Child

Dermal

NA NA

Dermal Mattress

Inhalation

HTM 0.0023 630

OTM 0.00031 4700

Adult

Lawn/Turf 

Delta 

Granules Reg. 

No. 4-422

Dermal

0.13 lb ai/A

or

0.000003 lb 

ai/ft2

NA NA

NA

Inhalation

Child

Dermal NA NA Inhalation

HTM 0.0002 7,600

OTM 0.00001 120,000

Soil Ingestion 0.000044 340,000

Episodic 

Ingestion 0.0127 120

Adult Lawn/Turf Dermal 0.13 lb ai/A NA NA Inhalation
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Table 6.2. Registered Residential Post-application Non-cancer Exposure and 

Risk Estimates for Deltamethrin.

Lifestage

Post-application Exposure 

Scenario Application 

Rate1

Dose 

(mg/kg/day)2 MOEs3 Combined MOEs

Use Site Route of 

Exposure

Child

K-Othrine SC 

Insecticide

Reg. No.432-

763

(0.06% ai)

Dermal NA NA

Inhalation

HTM 0.002 750

OTM 0.00006 25,000

Soil Ingestion 0.000034 340,000

Adult

4% 

Deltamethrin 

Pet Collar 

(Reg. No. 

68451-1)

Dermal

0.0024

lb ai/pet 

NA NA Inhalation

Child

Dermal NA NA Inhalation

HTM

(small dog) 0.000014 11,000

HTM 

(medium size 

dog)

0.0000058 26,000

HTM

(large dog) 0.0000037 400,000

1 Based on registered or proposed label.

2 Dose (mg/kg/day) equations: see Appendixes B-D for specific equations used by exposure scenario.

3 MOE = POD (mg/kg/day) ÷ Dose (mg/kg/day).

Turf Transferable Residue (TTR) Data

In accordance with 40CFR §158, TTR data are required for all occupational (e.g., sod farms, golf

courses, parks, and recreational areas) or residential turf uses that could result in post-application

exposure to turf. In the absence of chemical-specific TTR data, EPA uses default values. The

2012 SOPs for Residential Pesticide Exposure Assessment includes an analysis of all TTR data, 

available at the time, which resulted in the selection of revised liquid and granular default values 

for the fraction of the application rate (FAR) available for transfer after a turf application. These 

values are based on an analysis of 59 TTR studies performed with the Modified California Roller 

Method (36 studies using liquids, 11 studies using wettable powders/water dispersible granules, 

and 12 studies using granules). The liquid results (N=131) indicate a range of FAR values from 

0.0005% to 6.1%, and the granular results (N=37) indicate a range of 0.00064% to 0.69%. In 

both the liquid and granular data, a large range of transferability is observed and this variability 

can potentially be attributable to many factors such as active ingredient, formulation, field 

conditions in the studies, weather conditions (e.g., humidity), or many other factors that are 

difficult to quantify. Although witnessed across multiple chemicals, this range in FAR values is 

not expected when considering TTR data for a single chemical. HED selected 1% and 0.2% as 

high-end default values for liquid and granular products, respectively. Because TTR data are not 

available for deltamethrin, EPA is using the default value of 1%. Although there may be a small 

degree of uncertainty in the use of the default TTR value for deltamethrin (i.e., there is a small 
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chance that the FAR value may exceed the applicable default value), it is likely that the healthprotective aspects of EPA’s residential post-application turf assessment methodology will more 

than compensate for this potential uncertainty (i.e., the methodology is likely to overestimate 

exposure by a factor greater than the factor by which the highest measured FAR values exceed 

the defaults). For example, when assessing residential post-application turf exposure, EPA 

assumes the following: exposures occur to zero-day (i.e., day of application) residues every day 

of the assessed exposure duration (i.e., EPA assumes that no dissipation or degradation occurs,

e.g., it doesn’t rain, the grass is not mowed, etc); individuals perform the same post-application 

activities performed in the turf transfer coefficient study day after day (e.g., tumbling, playing on 

turf with toys, etc.); and individuals engage in these post application activities for a high-end 

amount of time every day that is represented by data reflecting time children spend outdoors and 

not specifically engaged in activities on turf, when in actuality, children do not spend all of their 

outdoor time on turf, and high-end levels of activity will not occur every day. 

Given the conservatisms discussed above and the potential compounding nature of these

conservatisms, EPA is able to rely upon the calculated exposure estimates with confidence that

exposure is not being underestimated. 

Since the estimated residential turf incidental oral post-application exposure for residential

turf using default TTR values for deltamethrin 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 = 750 compared to the LOC of 3000), future refinements of this post-application incidental 

oral exposure for deltamethrin may be necessary due to increased use of deltamethrin or 

advances in EPA risk assessments. Therefore, EPA is requiring the 40 CFR § 158 TTR

requirement to facilitate any necessary exposure assessment refinements 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

The recommended residential exposure for use in the adult aggregate assessment reflects the 

inhalation handler exposure resulting from the flea control scenario (i.e., treatment of lawns/turf 

and gardens/trees by manually pressurized handgun and backpack). This scenario resulted in an

MOE of 4,300 and is not of concern. 

The incidental oral (hand-to-mouth) post-application exposure scenario for the control of bed 

bugs was selected to estimate the child aggregate assessment. This scenario resulted in an MOE

of 630 and is not a risk of concern. A summary of the residential risk estimates for use in the 

aggregate assessment is provided in Table 6.3.

Table 6.3. Recommendation for Residential Exposures to be Included in the Deltamethrin Aggregate Assessment 

Lifestage

Residential Handler Residential Post-application 

Dose (mg/kg/day) MOE Dose (mg/kg/day) MOE

Dermal Inhalation Total Dermal Inhalation Total Dermal Inhala

tion Oral Total Dermal Inhalation Oral Total

Back Pack – Garden and Trees Bed Bug Scenario (Indoor)

Adult Male NA 0.00034 NA NA 4,300 NA NA N/A N/A NA NA N/A N/A Adult Female NA

Child N/A 0.002 630
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6.4 Residential Bystander Post-application Inhalation Exposure

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby outdoor pesticide applications. The agency sought expert advice and input on 

issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and 

Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s 

final report on March 2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109

meeting.html). The Agency has evaluated the SAP report and has developed a Volatilization 

Screening Tool and a subsequent Volatilization Screening Analysis 

(http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2014-0219). During Registration 

Review, the Agency will utilize this analysis to determine if data (i.e., flux studies, route-specific 

inhalation toxicological studies) or further analysis is required for deltamethrin.

6.5 Spray Drift

There is no potential for spray drift associated with the proposed use on finfish. However, spray 

drift is a potential source of exposure to those nearby pesticide applications of deltamethrin to 

agricultural field crops. 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 and airblast) employed for deltamethrin. 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). 1 The 

Agency has also developed a policy on how to appropriately consider spray drift as a potential 

source of exposure in risk assessments for 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. The approach is outlined in the revised (2012) Standard Operating Procedures 

For Residential Risk Assessment (SOPs) - Residential Exposure Assessment Standard Operating 

Procedures Addenda 1: Consideration of Spray Drift. This document outlines the quantification 

of indirect non-occupational exposure to drift.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate 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.

 

1 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
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7.1 Acute Aggregate Risk

Acute aggregate risk of exposure to deltamethrin 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,

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. For the short-term 

aggregate assessment for adults, residential handler inhalation exposure needs to be combined 

with background exposure from food and water. For the short-term aggregate assessment for 

children, post-application incidental oral exposure (i.e., hand to mouth transfer) needs to be 

combined with background exposure from food and water. The chronic dietary exposure 

estimates serve as the background dietary exposure. Of the population subgroups comprised of 

adults, the U.S. population has the highest dietary exposure estimate. Of the population 

subgroups comprised of infants and children, the subgroup with the highest dietary exposure 

estimate is Children 1-2 years old. As the oral and inhalation endpoints and points of departure 

are the same, the exposures for both adults and children can be added to determine the total 

exposure. The LOC for adult populations is 100. The MOEs for the general U.S. population and 

Females 13-49 are 2,500 and 2,800, respectively. These MOEs are not of concern. The LOC for 

children < 6 years old is 300. The MOE for Children 1-2 years old is 530 and is not of concern. 

A summary of the aggregate risk estimates is provided in Table 7.2.

Table 7.2 Short-Term Aggregate Risk Calculations

Oral and Inhalation Endpoints and Points of Departure Are the Same

Population

Short-Term Scenario

BMDL1SD

mg/kg/day LOC1

Max 

Allowable 

Exposure2

mg/kg/day

Average Food 

and Water 

Exposure 

mg/kg/day

Residential 

Exposure 

mg/kg/day3

Total 

Exposure 

mg/kg/day4

Aggregate 

MOE (food, 

water, and 

residential)5

U.S. Population 1.49 100 0.0149 0.000254 0.00034 0.000594 2,500

Females 13-49 1.49 100 0.0149 0.000192 0.00034 0.000532 2,800

Children 1-2 1.49 300 0.005 0.000822 0.002 0.002822 530

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 Maximum Allowable Exposure (mg/kg/day) = NOAEL/LOC

3 Residential Exposure = Oral exposure (children) or Inhalation Exposure (adults). See Table 6.3 for residential 

exposure estimates.

4 Total Exposure = Avg Food & Water Exposure + Residential Exposure

5 Aggregate MOE = BMDL1SD (1.49 mg/kg/day) ÷ (Avg Food & Water Exposure + Residential Exposure)

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 
Deltamethrin Human Health Risk Assessment DP No. D413048

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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.

Deltamethrin is included in the pyrethroid/pyrethrin cumulative risk assessment (CRA). The 

proposed import tolerance on finfish has an insignificant impact on the 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. Although there are residential uses for deltamethrin,

the proposed import tolerance for finfish will have no impact on the residential component of the 

cumulative risk estimates. In order to determine if the registered deltamethrin indoor and turf 

uses 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

deltamethrin relative potency factor (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.2 of the 2011 pyrethroid CRA were 

compared with the MOEs currently driving turf and indoor crack and crevice exposures and risks

in Table 6.4.7a from the pyrethroid CRA. Adult handler exposures and risks estimates are 

currently driven by cyfluthrin turf use (i.e. mixing/loading/applying via hose-end sprayer) with a 

dermal MOE of 9,200 and combined (dermal + inhalation) MOE of 8,900, which are lower than 

the estimated deltamethrin dermal MOE of 15,000 and combined MOE of 500,000. Adult and 

child dermal post-application exposure and risk are also currently driven by cyfluthrin turf use 

with an MOE of 4,500 and 3,000 respectively. For children <6 years old, hand-to-mouth postapplication exposure and risk estimates are currently driven by the cyhalothrin indoor crack and 

crevice use with an MOE of 9,700, which is lower than the estimated deltamethrin MOE of

16,000. A summary of these MOEs is presented in Appendix Table A.2, while the detailed 

calculations for deltamethrin are presented in Appendix Table A.3. In all cases, the estimated

deltamethrin 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 continues to support the previous 

assessment, and concludes that the registered deltamethrin use will not significantly contribute to 

the overall findings in the 2011 pyrethroid CRA.

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 the single chemical. In addition, for the deltamethrin risk 

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

derive the POD. Additionally, the POD selected for deltamethrin is specific to deltamethrin, 

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. 

Dietary exposure to deltamethrin residues resulting from the proposed import tolerance on finfish
Deltamethrin Human Health Risk Assessment DP No. D413048

Page 43 of 64

will contribute very little to the dietary exposure to deltamethrin alone. As a result, the proposed 

tolerance will make an insignificant contribution to dietary risk to the pyrethroids as a whole.

9.0 Occupational Exposure/Risk Characterization

There is no occupational exposure associated with this action to establish tolerances on imported 

finfish; therefore, an occupational exposure assessment was not completed.

10.0 References

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Registration) for Residues Resulting from Use of the Insecticide on Imported Finfish. Summary 

of Analytical Chemistry and Residue Data., 6/17/2014

D420895, Deltamethrin. Acute and Chronic Aggregate Dietary (Food and Drinking Water) 

Exposure and Risk Assessment for the Proposed Use of Deltamethrin Without U.S. Registration 

on Finfish, D. Dotson, 8/4/2014

M. Collantes, D418867, Revised Residential Exposure Assessment to Support A Tolerance 

without a U.S. Registration on Imported Fish, June 11, 2014.

D335136, J. Melendez, Tier I Estimated Drinking Water Concentrations of Deltamethrin for the 

Use in the Human Health Risk Assessment: IR-4 Tolerance Petition for the Use of Deltamethrin 

on Flax, 4/24/2007

K. Whitby, D394576, Pyrethroid Cumulative Risk Assessment, 10/4/2011

TXR# 0056944, Deltamethrin: Summary of Hazard and Science Policy Council (HASPOC) 

Meeting of February13, 2014: Recommendation on the Requirements for a Subchronic 

Inhalation Study, K. Rury, 4/29/2014

Anand, S. S., J. V. Bruckner, W. T. Haines, S. Muralidhara, J. W. Fisher and S. Padilla (2006). 

“Characterization of deltamethrin metabolism by rat plasma and liver microsomes.”

Toxicol Appl Pharmacol 212(2): 156-166.

Cao, Z., T. J. Shafer, K. M. Crofton, C. Gennings and T. F. Murray (2011a). “Additivity of 

Pyrethroid actions on sodium influx in cerebrocortical neurons in primary culture”

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Cao, Z., T. J. Shafer and T. F. Murry (2011b). “Mechanisms of pyrethroid insecticide-induced 

stimulation of calcium influx in neocortical neurons.” J Pharmacol Exper Ther 336(1): 197-205.

Choi, J.-S. and D. M. Soderlund (2006). “Structure-activity relationships for the action of 11 

pyrethroid insecticides on rat Nav1.8 sodium channels expressed in Xenopus oocytes.”

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Crofton, K. M., L. S. Kehn and M. E. Gilbert (1995). “Vehicle and route dependent effects of a 

pyrethroid insecticide, deltamethrin, on motor function in the rat.” Neurotoxicol Teratol 17(4) 

489-495.

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B. Conolly and R. Tornero-Velez (2010). “Physiologically based pharmacokinetic modeling of 

deltamethrin: Development of a rat and human diffusion-limited model.” Toxicol Sci 115(2): 

330-343.

Goldin, A. L., R. L. Barchi, J. H. Caldwell, F. Hofmann, J. R. Howe, J. C. Hunter, R. G. Kallen, 

G. Mandel, M. H. Meisler, Y. B. Netter, M. Noda, M. M. Tamkun, S. G. Waxman, J. N. Wood, 

and W. A. Catterall (2000). “Nomenclature of voltage-gated sodium channels.” Neuron 28(2): p. 

365-368.

Goldin, A. L. (2002). “Evolution of voltage-gated Na+ channels.” J Exp Biol 205(5): p. 575

Koukouritaki, S. B., J. R. manro, S. A. Marsh, J. C. Stevens, A. E. Rettie, D. G. McCarver, and 

R. N. Hines (2004). “Developmental expression of human hepatic CYP2C9 and CYP2C19.” J 

Pharmacol Exp Ther 308(3): p. 965-974. 

Lawrence, L. and J. Casida (1982). “Pyrethroid toxicology: Mouse intracerebral sturcturetoxicity relationships.” Pestic Biochem Physiol 18: 9-14.

Lund, A. and T. Narahashi (1982). “Dose-dependent interaction of the pyrethroid isomers with 

sodium channels of squid axon membranes.” Neurotoxicology 3(1): 11-24.

Meacham, C. A., P. D. Brodfuehrer, J. A. Watkins and T. J. Shafer (2008). “Developmentallyregulated sodium channel subunits are differentially sensitive to [alpha]-cyano containing 

pyrethroids.” Toxicology and Applied Pharmacology 231: 273-81.

Mirfazaelian, A., K. B. Kim, S. S. Anand, H. J. Kim, R. Tornero-Velez, J. V. Bruckner, and J. 

W. Fisher (2006). “Development of a physiologically based pharmacokinetic model for 

deltamethrin in the adult male Sprague-Dawley rat.” Toxicol Sci 93(2): p. 432 - 442.

Salgado, V., M. Herman and T. Narahashi (1989). “Interactions of the pyrethroid fenvalerate 

with nerve membrane sodium channels: Temperature dependence and mechanism of 

depolarization.” Neurotoxicology 10(1): 1-14.

Sample, B. E. and C. A. Arenal (1999). “Allometric Models for Interspecies Extrapolation of 

Wildlife Toxicity Data.” Bull Environ Contam Toxicol 62: 653-663.

Scollon, E. J., J. M. Starr, K. M. Crofton, M. J. Wolansky, M. J. DeVito, and M. F. Hughes 

(2011). “Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in 

the rat.” Toxicology 290: 1-6.

Shafer, T. J., D. Meyer and K. M. Crofton (2005). “Developmental neurotoxicity of pyrethroid 

insecticides: critical review and future needs.” Environ Health Persp 113(2): 123-136.
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Sheets, L. P., J. D. Doherty, M. W. Law, L. W. Reiter and K. M. Crofton (1994). “Agedependent differences in the susceptibility of rats to deltamethrin.” Toxicol Appl Pharmacol

126(1): 186-190.

Soderlund, D., J. Clark, L. Sheets, L. Mullin, V. Piccirillo, D. Sargent, J. Stevens and M. Weiner 

(2002). “Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment.” 

Toxicology 171(1): 3 - 59.

Song, J. H. and T. Narahashi (1996). “Modulation of sodium channels of rat cerebellar purkinje 

neurons by the pyrethroid tetramethrin.” Journal of Pharmacology and Experimental 

Therapeutics 277: 445-53.

Tabarean, I. V. and T. Narahashi (1998). “Potent modulation of tetrodotoxin-sensitive and 

tetrodotoxin-resistant sodium channels by the Type II pyrethroid deltamethrin.” J Pharmacol 

Exp Ther 284(3): 958-965.

Tan, J. and D. M. Soderlund (2009). “Human and rat Nav1.3 voltage-gated sodium channels 

differ in inactivation properties and sensitivity to the pyrethroid insecticide tefluthrin.”

Neurotoxicology 30(1): 81-89.

Tornero-Velez, R., A. Mirfazaelian, K.-B. Kim, S. S. Anand, H. J. Kim, W. T. Haines, B. James 

V and J. W. Fisher (2010). “Evaluation of deltamethrin kinetics and dosimetry in the maturing 

rat using a PBPK model.” Toxicol Appl Pharmacol 244: 208-217.

USEPA, 2007, Meeting Minutes: FIFRA SAP Meeting on assessing approaches for the 

development of PBPK models of pyrethroid pesticides. Document ID: EPA-HQ-OPP-2007-

0388-0049.

USEPA, 2012, Benchmark Dose Technical Guidance EPA/100/R-12/001.

Verschoyle, R. D. and W. N. Aldridge (1980). “Structure-activity relationships of some 

pyrethroids in rats.” Arch Toxicol 45(4): 325-329.

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functional observational battery study of twelve commercial pyrethroid insecticides in male rats 

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pyrethroids on motor function in rats.” Toxicol Sci 89(1): 271 - 277.

Wolansky, M. J. and J. A. Harrill (2008). “Neurobehavioral toxicology of pyrethroid insecticides 

in adult animals: A critical review.” Neurotoxicol Teratol 30(2): 55-78.

Yang, D., R. E. Pearce, X. Wang, R. Gaedigk, Y. J. Wan, and B. Yan (2009). “Human 

carboxylesterases HCE1 and HCE2: Ontogenic expression, inter-individual variability and 
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differential hydrolysis of oseltamivir, aspirin, deltamethrin and permethrin.” Biochem 

Pharmacol 77 (2): p. 238-247.

de Zwart, L., M. Scholten, J. G. Monbaliu, P. P. Annaert, J. M. Van Houdt, I. Van den Wyngaert, 

L. M. De Schaepdrijver, G. P. Bailey, T. P. Coogan, W. C. Coussement, and G. S. Mannens 

(2008). “The ontogeny of drug metabolizing enzymes and transporters in the rat.” Reprod 

Toxicol 26(3-4): p. 220-230.
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Appendices

Appendix A: Toxicology Profile

Appendix A.1. Toxicology Data Requirements

Toxicology Requirements for Deltamethrin

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

no

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 (Rat)...................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity: Gene Mutation - bacterial ...............................

870.5300 Mutagenicity: Gene Mutation - mammalian ..........................

870.5375 Mutagenicity: Structural Chromosomal Aberrations .............

870.5385 Mutagenicity: Structural Chromosomal Aberrations .............

870.5500 Mutagenicity: Other Genotoxic Effects .................................

870.5550 Mutagenicity: Other Genotoxic Effects .................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.6100 Acute Delayed Neurotoxicity (Hen) ......................................

870.6100 90-Day Neurotoxicity (Hen)..................................................

870.6200 Acute Neurotoxicity Screening Battery (Rat) ........................

870.6200 90 Day Neuro. Screening Battery (Rat) .................................

870.6300 Developmental Neurotoxicity................................................

no

no

yes

yes

yes

-

-

yes

yes

yes

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

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

870.7800 Immunotoxicity.......................................................................

yes

yes

yes

yes

yes

yes
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Appendix A2. Toxicity Profile Tables

Table A2.1 Acute Toxicity of Deltamethrin

Guideline No./Study Type MRID Results Toxicity 

Category

870.1100 Acute oral toxicity (rat) 41651019

00070734

LD50 = > 5000 mk/kg (1% aqueous 

methyl cellulose)

LD50 = 66.7 mg/kg (M), 86 mg/kg 

(F) (polyethylene glycol)

LD50 = 128.5 mg/kg (M), 138.7 

mg/kg (F) (sesame oil) 

IV

II

870.1200 Acute dermal toxicity (rat) 41651020 LD50 = >2000 mg/kg III

870.1300 Acute inhalation toxicity (rat) 41651021

00070734

LC50 = 2.2 mg/L

LC50 = 0.6 mg/L

III

II

870.2400 Acute eye irritation (rabbit) 41651022 Mild/moderate eye irritant III

870.2500 Acute dermal irritation (rabbit) 41651023 Not a dermal irritant IV

870.2600 Skin sensitization (guinea pig) 41651024 Not a dermal sensitizer NA

Table A2.2 Subchronic, Chronic, and Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/Classification 

/Doses

Results

870.3100

90-Day oral toxicityrat

00098103 (1977)

Acceptable/non-guideline (stability 

and purity data absent)

M/F: 0, 0.1, 1.0, 2.5, 10.0 

mg/kg/day

NOAEL = 2.5 mg/kg/day

LOAEL = 10 mg/kg/day based on increased 

hypersensitivity to sound in males and 

females at week 6.

870.3150

90-Day oral toxicitydog 

00098104 (1977)

Acceptable/non-guideline (agent 

purity not listed, too few animals 

(n=3 per sex/group), number of 

required observations were absent)

M/F: 0, 0.1, 1.0, 2.5, 10 mg/kg/day

NOAEL = 1 mg/kg/day

LOAEL = 2.5 mg/kg/day based on pupil 

dilation, depressed patellar reflex, and an 

increased incidence of diarrhea and vomiting. 

870.3200

21-Day dermal 

toxicity-rat

42773901 (1993)

Acceptable/guideline

M/F: 0, 100, 300, 1000 mg/kg/day

Systemic NOAEL = > 1000 mg/kg/day (limit 

dose)

The dermal NOAEL was not established: 

signs of local irritation (paresthesia) seen at 

all doses.

LOAEL = not identified.

870.3250

90-Day dermal toxicity

NA NA
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Table A2.2 Subchronic, Chronic, and Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/Classification 

/Doses

Results

21-Day inhalation 

toxicity-rat

00098089 (1978)

Unacceptable/non-guideline

(Concerns over the distribution of 

deltamethrin inside the exposure 

chamber, particle size (no MMAD 

or GSD reported), and lack of 

incidence data reported for clinical 

findings).

M/F: 0, 0.003, 0.0096, 0.0563 mg/L 

for 6 h/day for 5 days/week

NOAEL = 0.003 mg/L (0.783 mg/kg/day)

LOAEL = 0.0096 mg/L (2.5 mg/kg/day) 

based on excessive salivation, hunched 

posture, peripheral vasodilation, aggressive 

behavior, hypersensitivity to noise, and 

scarring of the ears.

870.3700a

Prenatal 

developmental-rat

41651025 (1990)

Acceptable/guideline

F: 1.0, 3.3, 7, 11 mg/kg/day

Maternal NOAEL = 3.3 mg/kg/day

LOAEL = 7 mg/kg/day based on increased 

salivation in 11/25 animals and convulsions in 

one animal (9 animals had convulsions at the 

next highest dose).

Developmental NOAEL >11 mg/kg/day 

LOAEL was not observed.

00098092 (1976)

Unacceptable/guideline (not noted 

if increased in delayed ossification 

were noted in fetal and/or litter 

incidences; neither route of 

administration or vehicle noted)

F: 0, 0.1, 1.0, 10 mg/kg/day

Maternal NOAEL = 1.0 mg/kg/day

LOAEL = 10 mg/kg/day based on slightly 

reduced body weight.

Developmental NOAEL = 1.0 mg/kg/day 

LOAEL = 10 mg/kg/day based on delayed 

ossification of the sternebrae; fetal losses 

increased from controls (2.2, 2.6, 2.7, and 

4%), though not statistically different.

870.3700b

Prenatal 

developmental-mouse

00098092 (1976)

Unacceptable/guideline (not noted 

if increased in delayed ossification 

were noted in fetal and/or litter 

incidences)

F: 0, 0.1, 1.0, 10 mg/kg/day

Maternal NOAEL = 10 mg/kg/day

LOAEL was not observed.

Developmental NOAEL = 0.1 mg/kg/day

LOAEL = 1.0 mg/kg/day based on decreased 

fetal weight, and delayed ossification of the 

sternebrae and paws.

870.3700b

Prenatal 

developmental-rabbit

45881901 (2001)

Acceptable/non-guideline

F: 0, 3, 10, 32 mg/kg/day in corn oil

Maternal NOAEL = 32 mg/kg/day

LOAEL = not established.

Developmental NOAEL  32 mg/kg/day

LOAEL = not established.
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Table A2.2 Subchronic, Chronic, and Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/Classification 

/Doses

Results

00098092 (1976)

Unacceptable/guideline (neither 

route of administration or vehicle 

noted; details of teratogenic 

parameters examined not given)

F: 0, 1, 4, 16 mg/kg/day

Maternal NOAEL = 16 mg/kg/day

LOAEL was not observed

Developmental NOAEL = 4 mg/kg/day

LOAEL = 16 mg/kg/day based on decreased 

fetal weights and increased fetal loss (6.6, 

18.5, 15.5, 10.2, 27.4%)

41651026 (1990)

Unacceptable/guideline

F: 0, 10, 25, 100 mg/kg/day in 

carboxymethylcellulose 

(deltametrhin dissolved in aqueous 

vehicles is reported to be less toxic)

Maternal NOAEL = 100 mg/kg/day

LOAEL = was not established.

Developmental NOAEL = 25 mg/kg/day

LOAEL = 100 mg/kg/day based on increases 

in delayed ossification and skeletal variations.

870.3800

Reproduction and 

fertility effects-rats

44398101 (1992)

Acceptable/guideline

M&F: 0, 5, 20, 80, 320 ppm

Parental animals

M: 0, 0.3, 1.3, 5.4, 21.2 mg/kg/day

F: 0, 0.4, 1.5, 6.1, 23.5 mg/kg/day

F1 animals

M: 0, 0.4, 1.4, 5.8, 24.9 mg/kg/day

F: 0, 0.4, 1.7, 6.7, 27.2 mg/kg/day

Parental/Systemic NOAEL = M: 5.4; F: 6.1 

mg/kg/day

LOAEL = M: 21.2; F: 23.5 mg/kg/day based 

on clinical signs in P generation (lesions on 

head, neck, and forearms in males and ataxia 

and hypersensitivity in females), decreased 

body weights in both the P and F1 generation, 

and gross pathological findings in the F1

generation. 

Offspring NOAEL = M: 5.8; F: 6.7 

mg/kg/day

LOAEL = M: 24.9; F: 27.2 mg/kg/day based 

on increased pup mortality (PND 8-14) in the 

F1 generation, increased mortality during the 

first 8 days post weaning in the F1 generation, 

clinical signs that were observed early in the 

post weaning period in the F1 generation 

(impaired righting reflex, urine stained fur, 

hyperactivity, splayed limbs, vocalization, 

and salivation) and decreased pup weights in 

the F1 (PND 4-21) and F2 generation (PND 7-

21).

Reproductive NOAEL = M: 24.9; F: 27.2 

mg/kg/day 

LOAEL = M: 21.2; F: 23.5 mg/kg/day.

 

870.4100a

Chronic toxicity-rat 

Same as Chronic 

Toxicity/Carcinogenicity- rat see 

below (870.4300)

See below (870.4300)
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Table A2.2 Subchronic, Chronic, and Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/Classification 

/Doses

Results

870.4100b

Chronic toxicity-dog 

44372601 (1993) 

Acceptable/guideline

M/F: 0, 1, 10, 50 mg/kg/day 

(gelatin capsule) -52 weeks

NOAEL = 1 mg/kg/day

LOAEL = 10 mg/kg/day based on chewing 

and scratching of extremities, abnormal gait 

with body tremors, and liquid feces.

870.4200b

Carcinogenicity-mouse

44372602 (1995) 

Acceptable/guideline

M/F: 0, 10, 100, 1000, 2000 ppm

M: 0, 1.5, 15.7, 155.4, 314.8 

mg/kg/day

F: 0, 2.0, 19.6, 189.3, 395.1 

mg/kg/day

NOAEL = 314.8/395.1 mg/kg/day ( 

M/F,HDT)

LOAEL = 603.4/738.8 mg/kg/day (M/F) 

based on decreased body weight observed in 

the 12-week range finding study.

No evidence of carcinogenicity, HDT 

assumed to be adequate to characterize the 

carcinogenic potential based on a 12-week 

range finding study in mice showing 

decreased body weight at 603.4/738.8 

mg/kg/day (M/F).

870.4300

Chronic/

Carcinogenicity-rat 

44398102 (1995)

Acceptable/guideline

M/F: 0, 25, 125, 500, 800 ppm

M: 0, 1.1 5.4, 22.2, 35.9 mg/kg/day

F: 0, 1.5, 7.3, 29.5, 47.1 mg/kg/day

NOAEL = 22.2/29.5 mg/kg/day (M/F)

LOAEL = 35.9/47.1 based on unsteady gait 

and splayed hindlimbs observed in the first 

few weeks of the study in male rats.

No evidence of carcinogenicity, HDT 

assumed to be adequate to characterize the 

carcinogenic potential based on a 13-week 

toxicity study in rats showing death, 

reduced body weight gains and marked 

neurological disturbances at 1000 ppm.

00098105 (1980)

Unacceptable/guideline (inadequate 

dosing)

M&F: 0, 2, 20, 50 ppm

M&F: 0, 0.1, 1.0, 2.5 mg/kg/day

NOAEL = >50 ppm (HDT)

LOAEL was not determined

No evidence of carcinogenicity.

870.5100 

Bacterial reverse 

mutation testS. typhimurium

42475902 (1980)

Acceptable/guideline

0, 2, 10, 50, 200, 1000, 5000 

μg/plate +/- S9

There was no evidence of an induced 

mutagenic effect at concentrations up to the 

limit dose (5000 μg/plate +/-S9). Compound 

precipitation seen at 200 μg/plate. 
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Table A2.2 Subchronic, Chronic, and Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/Classification 

/Doses

Results

870.5375

In vitro mammalian 

chromosome 

aberration testChinese hamster ovary 

(CHO) cells

41651027 (1989)

Acceptable/guideline

0, 19, 38, 75, 150 μg/mL +/- S9

There was no evidence of an induced 

mutagenic effect up to cytotoxic 

concentrations (38 μg/mL -S9; 150 μg/mL 

+S9). Levels 75 μg/mL were insoluble.

Other Genotoxicity 

870.5550

Bacterial DNA 

damage/repairE. coli

42475902 (1980)

Acceptable/guideline

0, 1250, 2500, 5000 μg/well +/- S9

There was no evidence of DNA 

repair/damage up to the limit dose (5000 

μg/well +/-S9). Compound precipitation seen 

at 200 μg/well. 

Other Genotoxicity 

870.5550 Unscheduled 

DNA synthesis in 

primary rat 

hepatocytes

41651028 (1989)

Acceptable/guideline

0, 0.13, 4.2, 13, 42, 130, 420, 1300, 

4200 μg/mL

There was no evidence that unscheduled 

DNA synthesis was induced up to insoluble 

concentrations ( 130 μg/mL).

870.6200a

Acute neurotoxicity 

screening battery-rats

44557901 (1998)

Acceptable/guideline

M&F: 0, 5, 15, 50 mg/kg

Neurotoxic NOAEL= 15 mg/kg/day

LOAEL = 50 mg/kg/day based on clinical 

signs during handling, open field, and sensory 

observations including, convulsions and 

tremors, increased salivation, soiled fur, 

impaired mobility, low arousal, decreased 

rearing, decreased fore- and hind-limb grip 

strength, and decreased body temperature.

870.6200b

Subchronic 

neurotoxicity

screening battery

44557902 (1998)

Acceptable/guideline

M&F: 0, 50, 200, 800 ppm

M: 0, 4, 14, 54 mg/kg/day

F: 0, 4, 16, 58 mg/kg/day

Neurotoxic NOAEL= M: 14; F: 16 mg/kg/day

LOAEL = M: 54; F: 58 mg/kg/day based on 

mortality, clinical signs, FOB findings, and 

decreased body weights, body weight gains, 

and food consumption.

870.6300

Developmental 

neurotoxicity

46814301 (2006)

Acceptable/Non-Guideline (pending 

review of positive-control data)

0, 20, 80, 200 ppm

0, 1.6, 6.8, 16.1 mg/kg/day 

(gestation and lactation)

Maternal NOAEL = 6.8 mg/kg/day. 

Maternal LOAEL = 16.1 mg/kg/day based 

on decreased body weight (6-7% on GD 13 

and GD 20).

Offspring NOAEL = 6.8 mg/kg/day 

Offspring LOAEL = 16.1 mg/kg/day based 

on decreased pre- and post-weaning body 

weight and increased incidence of 

vocalizations (males) during FOB.
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Table A2.2 Subchronic, Chronic, and Other Toxicity Studies

Guideline No./ Study 

Type

MRID No. (year)/Classification 

/Doses

Results

870.7485

Metabolism and 

pharmacokinetics-rats

41677401 (1990)

Acceptable/guideline

M/F: 0.55, 5.5 mg/kg

The test material was relatively well 

absorbed. Excretion was almost complete 

within 48 hours. Approximately 36-59% of 

the dose was found in feces and an 

approximately equal amount in urine. 

Absorbed deltamethrin was cleaved by 

hydrolysis at the ester site followed by rapid 

sulfate and glucuronide conjugation.

870.7600

Dermal penetration

NA NA

870.7800

Immunotoxicity

48988205 (2012)

Acceptable/guideline

F: 0, 8.3, 23.5, 48.3 mg/kg/day

NOAEL = 48.3 mg/kg/day

LOAEL = not established.

No evidence of systemic toxicity or 

immunotoxicity was observed in the study up 

to the highest dose tested.

Literature studies

Wolansky et al.-Acute 

Oral Toxicity in RatsMotor Activity

47885701 (2006)

Acceptable/non-guideline

0, 0.03, 0.1, 0.3, 1, 3, and 10 mg/kg 

Vehicle: Corn oil

Volume: 1 ml/kg

BMDL1SD = 1.49 mg/kg

BMD1SD = 2.48 mg/kg based on decreased 

motor activity.

WIL Study- Acute 

Oral Toxicity in RatsFOB

47050504 (2006) 

Acceptable/Non-Guideline

0, 12.5, 25, and 35 mg/kg via gavage 

in corn oil (5 mL/kg)

BMDL20 = 10.5 mg/kg

BMD20 = 14.5 mg/kg based on multiple FOB 

changes.
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A.3 Toxicological Doses and Endpoints for Use in Human Risk Assessments

Figure A3.1 Decision tree for evaluating potential toxicity studies for endpoint selection

Hazard 

Identification and Endpoint Selection A.3.1 Acute Reference Dose (aRfD) –All Populations 

Including Infants and Children and Females Age 13-49 

Study Selected: Acute Motor Activity (Wolansky et al., 2006)

MRID #: 47885701

Dose and Endpoint for Risk Assessment: BMDL1SD = 1.49 mg/kg, based on decreased motor 

activity seen at 3 mg/kg. 

Uncertainty Factor:

Adults and Children ≥ 6 years old: 100X (1X FQPA, 10X interspecies extrapolation, 10X 

intraspecies variability)

Acute RfD = 

100( )

1.49 /

UF

mg kg = 0.015 mg/kg

Children < 6 years old: 300X (3X FQPA, 10X interspecies extrapolation, 10X intraspecies 

variability)

Wolansky data: BMDL1SD = 0.51 mg/kg

6 doses, well-defined Dose-Response Curve

BMD analysis instead of N/L approach

High quality motor activity data, objective, time of peak effect

Long-Evans, sensitive strain

1 ml/kg of corn oil, greater response compared to larger 

dosing volumes (i.e., 5 ml/kg)

Compare available acute studies to 

other durations/species/effects

ACN: NOAEL = 15 mg/kg

WIL: BMDL20 = 10.5 mg/kg

Repeated dosing studies?

Other species?

1 yr dog: NOAEL = 1 mg/kg/day

Developmental rat: NOAEL = 3.3 mg/kg/day

DNT rat: NOAEL = 6.8 mg/kg/day

SCN rat: NOAEL = 14 mg/kg/day

90-day rat: NOAEL = 2.5 mg/kg/day

2-gen reproduction rat: NOAEL = 5.4 mg/kg/day

2 yr rat : NOAEL = 22.2 mg/kg/day

1 yr dog: NOAEL = 1 mg/kg/day

Deltamethrin

Other acute studies?
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Comments about Study/Endpoint: The Wolansky study was selected based on decreased 

motor activity observed within 3 hours following an acute exposure. BMD analysis was 

conducted and a BMDL1SD value of 1.49 mg/kg was determined. Endpoints for risk assessment 

are not typically selected from literature studies. However, the Wolansky et al. (2006) study is 

uniquely appropriate based on: 1) the large number of dose levels (6); 2) the large number of 

animals (8-18 per group); 3) neurotoxicity was determined at the time to peak effect (2 hours 

post dosing); and 4) motor activity is recognized as one of the most common techniques for 

determining pyrethroid neurotoxicity in laboratory animal studies (Wolansky and Harrill 2008). 

Furthermore, the selection of the BMDL1SD from the Wolansky study is supported by multiple 

guideline and literature studies. The ACN, chronic dog, and WIL studies were all considered for 

risk assessment since they all had effects that were observed within hours following dosing. 

However, these studies all had higher NOAELs and were not selected for risk assessment. The 

chronic dog study had a slightly lower NOAEL (1 mg/kg/day); however, the human equivalent 

dose based on allometric scaling was actually higher for the chronic dog study (0.61 mg/kg/day) 

compared to the Wolansky study (0.43 mg/kg). The WIL study and the ACN study both used 

relatively high vehicle volumes (5 ml/kg vs. 1 ml/kg in Wolansky) which likely impacted the 

absorption characteristics of deltamethrin, thereby increasing the POD. Since there is no apparent 

increase in hazard from repeated/chronic exposures to deltamethrin, the acute dietary exposure 

assessment is protective of chronic dietary exposures since acute exposure levels are higher than 

chronic exposure levels. Accordingly, a chronic dietary risk assessment was not conducted.

A.3.2 Incidental Oral Exposure (Short-Term) 

Study Selected: Acute Motor Activity (Wolansky et al., 2006)

MRID #: 47885701

Dose and Endpoint for Risk Assessment: BMDL1SD = 1.49 mg/kg, based on decreased motor 

activity seen at 3 mg/kg.

Uncertainty Factor:

Adults and Children < 6 years old: 300X (3X FQPA, 10X interspecies extrapolation, 10X 

intraspecies variability)

Comments about Study/Endpoint: The Wolansky study was selected based on decreased 

motor activity observed within 3 hours following an acute exposure. BMD analysis was 

conducted and a BMDL1SD value of 01.49 mg/kg was determined. Endpoints for risk 

assessment are not typically selected from literature studies. However, the Wolansky et al. 

(2006) study is uniquely appropriate based on: 1) the large number of dose levels (6); 2) the 

large number of animals (8-18 per group); 3) neurotoxicity was determined at the time to peak 

effect (2 hours post dosing); and 4) motor activity is recognized as one of the most common 

Acute RfD = 

300( )

1.49 /

UF

mg kg = 0.005 mg/kg
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techniques for determining pyrethroid neurotoxicity in laboratory animal studies (Wolansky and 

Harrill 2008). Furthermore, the selection of the BMDL1SD from the Wolansky study is 

supported by multiple guideline and literature studies. The short-term oral studies, 

developmental and reproduction studies, and the chronic oral studies were all considered for 

risk assessment. However, the Wolansky study provided the most appropriate NOAEL that is 

protective of potential developmental/offspring effects, as well as other systemic effects 

observed in the toxicology database.

A.3.3 Dermal Exposure (Short-Term) 

A 21-day dermal study in rat for deltamethrin is available for consideration. However, no 

treatment-related findings were observed at the limit dose. There was also no toxicity observed 

following acute dermal exposure to deltamethrin up to a dose of 2000 mg/kg. Therefore, a 

dermal hazard was not identified for deltamethrin and no dermal risk assessment will be 

conducted. This finding is consistent with the toxicology profile of many pyrethroids. No 

dermal hazard has been identified for fenpropathrin, zeta-cypermethrin, allethrin, and prallethrin. 

Typically pyrethroids have a low absorption value of ≤ 5% and a high rate of metabolism. 

Deltamethrin had a slightly higher absorption value of 11.3%, although the majority of the 

radioactivity measured was at the skin site (10.6%). This is typical of the pyrethroids, as they are 

lipophilic and much of the radioactivity measured in the skin of dermal penetration studies with 

pyrethroids is captured in the upper dermal layers and not available for absorption or systemic 

circulation. 

A.3.4 Inhalation Exposure (Short-Term)

Study Selected: Acute Motor Activity (Wolansky et al., 2006)

MRID #: 47885701

Dose and Endpoint for Risk Assessment: BMDL1SD = 1.49 mg/kg, based on decreased motor 

activity seen at 3 mg/kg.

Uncertainty Factor:

Adults and Children ≥ 6 years old: 100X (1X FQPA, 3X interspecies extrapolation, 10X 

intraspecies variability)

Children < 6 years old: 300X (3X FQPA, 10X interspecies extrapolation, 10X intraspecies 

variability)

Comments about Study/Endpoint: An acceptable inhalation study was not available for 

deltamethrin. The HASPOC waived the requirement for a subchronic inhalation study (TXR#

0056944). In the absence of an inhalation study an oral study is being used. The Wolansky 

study was selected based on decreased motor activity observed within 3 hours following an 

acute exposure. BMD analysis was conducted and a BMDL1SD value of 1.49 mg/kg was 

determined. Endpoints for risk assessment are not typically selected from literature studies. 
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However, the Wolansky et al. (2006) study is uniquely appropriate based on: 1) the large 

number of dose levels (6); 2) the large number of animals (8-18 per group); 3) neurotoxicity 

was determined at the time to peak effect (2 hours post dosing); and 4) motor activity is 

recognized as one of the most common techniques for determining pyrethroid neurotoxicity in 

laboratory animal studies (Wolansky and Harrill 2008). Furthermore, the selection of the 

BMDL1SD from the Wolansky study is supported by multiple guideline and literature studies.

The short-term oral studies, developmental and reproduction studies, and the chronic oral 

studies were all considered for risk assessment. However, the Wolansky study provided the 

most appropriate NOAEL that is protective of potential developmental/offspring effects, as well 

as other systemic effects observed in the toxicology database. Absorption and toxicity via the 

inhalation route are assumed to be equal to toxicity via the oral route.
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Appendix A.4. 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.

The active ingredient, deltamethrin, was assessed in the November 2011 pyrethroid cumulative 

risk assessment. The Agency has determined based on its chemical structure and based on the 

observation of neurobehavioral effects consistent with Type II pyrethroids, that deltamethrin

should be included in the CMG for this class of pesticides. As such, the Agency must consider 

the potential contribution of deltamethrin to the cumulative risk assessment. No new residential 

use scenarios have been proposed or registered since the 2011 pyrethroid CRA. Therefore, there 

has been no change to the overall findings in the pyrethroid CRA due to contribution of 

deltamethrin uses.

A.4.1. Cumulative Hazard Assessment: Relative Potency Estimation for Deltamethrin

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 which 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 which are from the same endpoint and same duration and to the 

extent possible any other factors which effect 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 was 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 

CRA because of the lack of specific relevance to the common mechanism of action for the 

pyrethroids. 
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In the CRA, deltamethrin was used as the index chemical. Deltamethrin stands out as having one 

of the most robust databases of guideline and literature studies. For example, multiple studies on 

deltamethrin have been identified examining in vivo neurotoxicity, in vitro sodium channel 

interaction, metabolism, pharmacokinetics following multiple routes of administration (oral, 

dermal, intravenous, intercerebral, etc.) and PBPK modeling. Furthermore, the deltamethrin 

PoD derived from the FOB data is of sufficiently high quality to minimize error or uncertainty in 

the cumulative risk estimates. 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). Therefore, for deltamethrin the RPF is 1.00. 

Table A.4.1: Pyrethroid RPF Comparison FOB vs. Motor Activity

Pyrethroid FOB Motor Activity

lambda-cyhalothrin 1.63 1.90 a

tefluthrin 1.36 1.11 a

cyfluthrin 1.15 1.14 a

bifenthrin 1.01 1.96 a

deltamethrin 1.00 1.00 a

fenpropathrin 0.50 0.33 a

metofluthrin 0.48 --

esfenvalerate 0.36 2.09 a

cypermethrin 0.19 0.23 a

tau-fluvalinate 1.00 --

cyphenothrin 0.15 --

d-allethrin 0.11 --

allethrin 0.11 0.03 a

prallethrin 0.10 --

permethrin 0.09 0.15 a

resmethrin 0.05 0.02 a

pyrethrins 0.02 --

imiprothrin 0.02 --

flumethrin -- 5.02 b

a Represents motor activity data from the Wolansky study

b Represents motor activity data from the flumethrin ACN study
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A.4.2. Cumulative Exposure and Risk Issues

In order to determine if the registered deltamethrin indoor and turf uses 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 deltamethrin 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.4.2.a were compared with the MOEs 

currently driving turf and indoor crack and crevice exposures and risks in Table 6.4.7a from the 

2011 pyrethroid CRA. Adult handler exposures and risks estimates are currently driven by 

cyfluthrin turf use (i.e. mixing/loading/applying via hose-end sprayer) with a dermal MOE of 

9,200 and combined (dermal + inhalation) MOE of 8,900, which are lower than the estimated 

deltamethrin dermal MOE of 15,000 and combined MOE of 500,000. Adult and child dermal 

post-application exposure and risk are also currently driven by cyfluthrin turf use with an MOE 

of 4,500 and 3,000 respectively. For children < 6 years old, hand-to-mouth post-application 

exposure and risk estimates are currently driven by the cyhalothrin indoor crack and crevice use

with an MOE of 9,700, which is lower than the estimated deltamethrin MOE of 16,000. A 

summary of these MOEs is presented in Appendix Table A.4.2.a while the detailed calculations 

for deltamethrin are presented in Appendix Table A.4.2.b. In all cases, the estimated

deltamethrin 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 continues to support the previous 

assessment and concludes that the registered deltamethrin use will not significantly contribute to 

the overall findings in the 2011 pyrethroid CRA.
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 Table A.4.2.a. Comparison of Deltamethrin MOEs with Pyrethroid Cumulative MOEs

Chemical Exposure 

Scenario Route of Exposure Population MOE Combined MOE

Registered Use Deltamethrin

Turf (EC) – M/L/A 

Hose-end Sprayer

Handler Dermal

Adult

15,000 500,000 Handler Inhalation 420,000

Post-application Dermal 7,700 NA

Post-application Dermal Child 5,300 4,600 Post-application HTM 36,000

CRA Cyfluthrin

Handler Dermal

Adult

9,200 8,900 Handler Inhalation 280,000

Post-application Dermal 4,500 NA

Post-application Dermal Child 3,000 2,700 Post-application HTM 21,000

Registered Use Deltamethrin

Indoor – M/L/A 

crack & crevice

Handler Dermal

Adult

87,000 66,000 Handler Inhalation 270,000

Post-application Dermal 70,000 NA

Post-application Dermal

Child

58,000

12,000

Post-application HTM 16,000

CRA

Cyfluthrin Handler Dermal 43,000 33,000 Handler Inhalation 140,00

Cyhalothrin

Post-application Dermal 43,000 NA

Post-application Dermal 36,000 7,600 Post-application HTM 9,700
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 Table A.4.2.b. Deltamethrin Screening Level “Cumulative” MOEs

Handler Exposure

Exposure 

Scenario

Application 

Rate

Amount 

Treated 

Daily 

(animals)

Baseline 

Dermal 

Unit 

Exposure 

(mg/lb ai)

Baseline 

Inhalation 

Unit 

Exposure 

(mg/lb ai)

Baseline Dermal 

Unit Exposure 

(mg/lb ai)

Baseline 

Inhalation 

Unit 

Exposure 

(mg/lb ai)

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

Adult- Turf 0.13

lb ai/A 0.5 15 0.024 0.98 0.3 0.0007 0.00068 15,000 2.23E-5 2.2E-5 470,000

Adult – Indoor 

C&C

0.0005

lb ai/gal 0.5 69 1.1 0.17 0.00275 0.0001 0.00012 87,000 3.8E-5 3.8E-5 270,000

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

Child - Turf

(6 > years old) 0.034 0.45 150 5.15E-5 0.13 0.9 4 0.5 13.9 11.4 0.00028 0.00028 36,000

Child – C&C

(6 > years old) 0.15 0.04 150 2E-5 0.13 5 4 0.5 20 11.4 0.00066 0.00066 16,000

Post-application Dermal Exposure

Exposure 

Scenario Application Rate Body Weight(kg)

Hours of 

Exposure

Conversion 

Factor 

(mg/ug)

DFR/TTR

(ug/cm2

DAT 0)

Transfer 

Coefficient

(cm2/hr)

Absorbed Dermal Dose 

(mg/kg/day)

Adjusted Dose 

(mg/kg/day) a

Adjusted 

MOE b

Child - Turf

(6> years old) 0.13 lb ai/A 11.4 0.9 0.001 0.0105 37,500 0.002 0.0019 35,000

Adult- Turf 0.13 lb ai/A 71.8 1.1 0.001 0.0105 130,000 0.0014 0.00135 77,000

Exposure 

Scenario

Surrogate Deposition 

(ug/cm2)

Conversion Factor 1 

(ug/lb)

Conversion 

Factor 2

(ft2to cm2)

Surface 

Residue 

(ug/cm2)

Fraction 

Transferred

Transfer 

Coefficient 

(cm2/hr)

Exposure 

Time 

(hr/day)

CF3

(mg/ug)

Adjusted Dose 

(mg/kg/day)

Adjusted

MOE

Child – C&C 0.2 4.5E+8 1.08E-3 0.2 0.02 2,000 5 1E-3 0.00018 58,000

Adult – C&C 0.2 4.5E+8 1.08E-3 0.2 0.02 6,800 8 1E-3 0.00015 70,000

a Doses were adjusted based on an estimated deltamethrin RPF of 5.02

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 Handler inhalation exposure is expected to be negligible from deltamethrin pet collars and, thus, a quantitative assessment was not performed.
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Appendix B. Physical/Chemical Properties

Table B.1. Physicochemical Properties of Technical Grade Deltamethrin.*

Parameter Value

Melting Point/Range (°C) 100-102

pH Not available.

Density (g/cm3at 25°C) 0.550

Water Solubility (ug/L at 25°C) <0.2

Solvent Solubility (% by weight at 20oC) Acetone 33

Alcohol 0.6

Isopropanol 0.2

Ethyl acetate 25

n-Hexane 0.2

Toluene 23

DMF 38

Dioxane 39

Vapor Pressure (mm Hg at 25oC) [mPa at 25°C] 1.5 x 10-8[1.24 x 10-5]

Dissociation Constant, pKa Does not dissociate.

Octanol/Water Partition Coefficient, KOW (at 25oC) 2.7 x 105

UV/Visible Absorption Spectrum Not available.

* Reference: MARC Briefing Memorandum; D284320; D. Dotson; 5 November 2002. 
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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.