UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DATE: 2/24/2015 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

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

Deltamethrin as a Mosquito Adulticide over Agricultural Crops. 

PC Code: 097805 

Decision No.: 484277 

Petition No.: 3F821 0 

DP Barcode: 0417556 

Registration No.: 432-RLGU 

Regulatory Action: Section 3 Registration 

Risk Assessment Type: Single Chemical Case No.: 7414 

Aggregate 

TXRNo.: NA 

MRIDNo.:NA 

CAS No.: 52918-63-5 

40 CFR: § 180.435 

FROM: 

THROUGH: 

TO: 

Douglas A. Dotson, Ph.D., Chemist J. f)~ Jaime D' Agostino, Ph.D., Toxicologis~_A. 4--

Margarita Collantes, M.S., Biologist~~ Jv 

Risk Assessment Branch II 

Health Effects Division (7509P) 

Chr

Healt

Risk 

istina 

Assessment 

h Effects 

Swartz, 

Division 

Branch 

Branch 

(7509

II 

Chief 

P) 

~ 

Olga Odiott!Richard Gebken, PM Team 10 

InvertebrateN ertebrate Branch (IVB2) 

Registration Division (7505P) 

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

human health risk assessment for the proposed use of deltamethrin as a wide-area mosquito 

adulticide in the airspace over agricultural crops. 

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. 
Deltamethrin Human Health Risk Assessment DP No. D417556 

Table of Contents 

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

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

2.1 

2.2 

2.2.1 

2.2.2 

2.2.3 

2.2.4 

2.3 

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

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

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

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

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

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

Label Recommendations ................................................ ........ ....... ..... ............ ........ ..... 9 

3.0 

3.1 

3.2 

3.3 

3.4 

3.5 

Introduction ............................. .... ........... .... .... ................ .... ............ ........................ ........... 10 

Chemical Identity ............................................................... ........... .... .... ........ .... .... ........ 1 0 

Physical/Chemical Characteristics ..... ....... .... .... .... ............ ............................................ 1 0 

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

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

Consideration of Environmental Justice ...................... ........ ........ ....... ..... .... .... .... .... ..... 14 

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

4.1 

4.2 

4.3 

4.3.1 

4.3.2 

4.3.3 

4.4 

4.4.1 

4.4.2 

4.4.3 

4.4.4 

4.5 

4.5.1 

4.5.2 

4.5.3 

4.5.4 

5.0 

5.1 

5.1.1 

5.1.2 

5.1.3 

5.1.4 

5.2 

5.3 

5.4 

5.4.1 

5.4.2 

5.4.3 

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

Toxicological Profile .................................................................................................... 16 

Pyrethroid Pharmacokinetic and Pharmacodynamic Profile ....................... .... ............. 17 

Pharmacokinetics ................................................................. .................... ................. 1 7 

Pharmacodynamics ........... .......................... ................ ........ .... ........ ........ .... ......... .... . 19 

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

Safety Factor for Infants and Children (FQPA Safety Factor) ..................................... 22 

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

Evidence ofNeurotoxicity ................................................. ................ ........ ........ .... ... 23 

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

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

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

Dose-Response and Hazard Assessment ... ........ ............ .... ....................................... 25 

Recommendation for Combining Routes of Exposure for Risk Assessment ........... 27 

Cancer Classification and Risk Assessment Recommendation ................................ 27 

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

Dietary Exposure and Risk Assessment ........................................................................... 28 

Metabolite/Degradate Residue Profile ............................................. ............. ................ 28 

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

Summary of Environmental Degradation ..... .... .... ............ ............... .... ................... 289 

Comparison of Metabolic· Pathways ............. ....................... .... ............ ............. ........ 29 

Residues of Concern Summary and Rationale ............................................. ........ ..... 30 

Food Residue Profile ..................................................................................................... 30 

Water Residue Profile .......................................................... ........ ........ ....... .................. 31 

Dietary Risk Assessment ....... .............................................................................. .... .... . 31 

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

Percent Crop Treated Used in Dietary Assessment.. ....... ........................ .... ........ ..... 33 

Acute Dietary Risk Assessment.. .. ....................................................................... .... . 34 

Page 2 of67 
Deltamethrin Human Health Risk Assessment DP No. D417556

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5.4.4 Chronic Dietary Exposure Assessment..................................................................... 34

5.4.5 Summary Table......................................................................................................... 35

6.0 Residential Exposure and Risk Estimates......................................................................... 35

6.1 Proposed Use: Wide-Area Mosquito Control.............................................................. 35

6.2 Residential Handler Exposure/Risk Estimates for Registered Uses............................. 37

6.3 Residential Post-Application Exposure/Risk Estimates for Registered Uses............... 39

6.4 Residential Risk Estimates for Use in Aggregate Assessment ..................................... 41

6.5 Spray Drift .................................................................................................................... 41

7.0 Aggregate Exposure/Risk Characterization...................................................................... 42

7.1 Acute Aggregate Risk................................................................................................... 42

7.2 Short-Term Aggregate Risk Estimates......................................................................... 42

8.0 Cumulative Exposure/Risk Characterization.................................................................... 43

9.0 Occupational Exposure/Risk Characterization ................................................................. 44

9.1 Occupational Handler Exposure/Risk Estimates.......................................................... 44

9.2 Occupational Post-application Risk Estimates ............................................................. 46

9.2.1 Occupational Post-application Inhalation Risk Estimates........................................ 46

9.2.2 Occupational Post-application Dermal Risk Estimates ............................................ 46

10.0 References......................................................................................................................... 46

Appendix A. Toxicology Profile.................................................................................................. 50

A.1 Toxicology Data Requirements .................................................................................... 50

A.2 Toxicity Profile Tables ................................................................................................. 51

A.3 Toxicological Doses and Endpoints for Use in Human Risk Assessments.................. 57

A.4 Pyrethroid Cumulative Screen ...................................................................................... 61

Appendix B. Physical/Chemical Properties................................................................................. 66

Appendix C. Review of Human Research ................................................................................... 67
Deltamethrin Human Health Risk Assessment DP No. D417556

Page 4 of 67

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. The registrant, Bayer Environmental Science, petitioned the 

Agency to amend 40CFR §180.435(a)(2) to include the use of deltamethrin as a wide-area

mosquito adulticide in the airspace over agricultural crops. Bayer further proposed that the 0.05 

ppm tolerance established for residues of deltamethrin in commodities resulting from the FHE 

use apply to the adulticide use as well. 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 
Deltamethrin Human Health Risk Assessment DP No. D417556

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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 

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 establishing a tolerance and for evaluating 

risk from the use of deltamethrin as a wide-area mosquito adulticide. Bayer submitted the results 

of residue trials that were performed on alfalfa, grass, and lettuce.

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 residential handler exposure scenarios associated with the new proposed mosquito 

control use because applications are to be made by federal, state, tribal, or local government 
Deltamethrin Human Health Risk Assessment DP No. D417556

Page 6 of 67

officials as well as the U.S. military. However, there is potential for residential post-application 

exposure resulting from mosquito control use. This document also includes handler and postapplication exposure assessments for existing residential uses (i.e., indoor, outdoor, pet, and 

paint additive) that reflect updates to HED’s 2012 Residential SOPs, along with policy changes 

for body weight assumptions, and updated inhalation and incidental oral toxicological endpoints 

and uncertainty factors (UFs). 

All post-application inhalation and incidental oral exposure estimates resulting from the 

proposed mosquito and fly control scenarios were assessed using the single maximum 

application rate of 0.0018 lb ai/acre and resulted in MOEs greater than their respective LOCs and 

are not of concern. 

All registered residential handler scenarios resulted in inhalation risk estimates greater than the 

LOC and are not of concern (i.e., margins of exposure (MOEs) are ≥ 100). Post-application 

inhalation exposure for adults and children is anticipated to be negligible for representative 

residential registered uses; therefore, a quantitative post-application inhalation exposure 

assessment was not performed. All the representative indoor/outdoor and pet residential use 

scenarios resulted in incidental oral (hand-to-mouth) post-application risk estimates for children 

ranging from an MOE of 630 to 400,000 and are not of concern. 

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

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

residues in background dietary 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 (CRA) for pyrethrins and pyrethroids

(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 

points of departure (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.

Systemic toxicity via the dermal route of exposure is not anticipated. Therefore, a dermal POD 

was not selected, and a quantitative dermal handler and post-application exposure assessment 

was not performed. Occupational assessments are based on inhalation exposures only. 

Occupational handler scenarios resulted in inhalation MOEs greater than the LOC (inhalation 

MOE ≥ 100) at baseline (i.e., no respirator) and are not of concern. 
Deltamethrin Human Health Risk Assessment DP No. D417556

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The proposed BES0668 Insecticide label specifies the use of portable, motorized backpack 

equipment adjusted to deliver Ultra Low Volume (ULV) particles of less than 100 microns. 

HED does not have unit exposure handler data for hand held fogging equipment. Therefore, 

chemical-specific data are needed to support this scenario, and constitute a data gap for 

deltamethrin. These data need to be submitted in accordance with the 40 CFR Part 158 data 

requirements.

Based on the Agency’s current practices, a quantitative non-cancer occupational post-application 

inhalation exposure assessment is not being performed for deltamethrin at this time. If new 

policies or procedures are put into place, the Agency might revisit the need for a quantitative 

residential post-application inhalation exposure assessment for deltamethrin.

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

to the establishment of a tolerance of 0.05 ppm for residues of deltamethrin in or on all 

commodities as a result of the mosquito adulticide use.

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

assessment to the extent possible. 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 SOPs (Turf/Lawn, Indoor Environments, and 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 has no objection to the establishment of a tolerance of 0.05 ppm for the use of deltamethrin 

as a wide-area mosquito adulticide over all crops.

2.1 Data Deficiencies

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

mosquito adulticide. 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 300), future refinements of this post-application exposure for 
Deltamethrin Human Health Risk Assessment DP No. D417556

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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.

HED does not have unit exposure handler data for hand held fogging equipment. Therefore, 

chemical-specific data are needed to support this scenario for occupational workers, and 

constitute a data gap for deltamethrin. These data need to be submitted in accordance with the 

40 CFR Part 158 data requirements.

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. 

2.2.2 International Harmonization

Harmonization of MRLs is not an issue for the proposed use of deltamethrin as a wide-area

mosquito alulticide, as established tolerance levels are not changing. Harmonization of existing 

tolerances will be addressed during registration review.

2.2.3 Recommended Tolerances

Currently, a tolerance of 0.05 ppm is established for residues of the insecticide 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-mphenoxybenzyl-(1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate and alphaR-deltamethrin[(R)-alpha-cyano-m-phenoxybenzyl-(1R,3R)-3-(2,2-dibromovinyl)-2,2-

dimethylcyclopropanecarboxylate] in or on all food/feed items (other than those covered by a 

higher tolerance as a result of use on growing crops) in food/feed handling establishments. The 

tolerance level does not need to be increased for the proposed use as a mosquito adulticide; 

however, the tolerance expression needs to be modified as discussed below.

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

§180.435[a][2], be amended to read as follows: 
Deltamethrin Human Health Risk Assessment DP No. D417556

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A tolerance of 0.05 ppm is established for residues of the insecticide 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,3R)-3-(2,2-dibromovinyl)-2,2-

dimethylcyclopropanecarboxylate and alpha-R-deltamethrin[(R)-alpha-cyano-mphenoxybenzyl-(1R,3R)-3-(2,2-dibromovinyl)-2,2-

dimethylcyclopropanecarboxylate] as follows:

(i) In or on all food/feed items (other than those covered by a higher tolerance as a 

result of use on growing crops) in food/feed handling establishments or as a widearea mosquito adulticide.

(ii) The insecticide may be present as a residue from application of deltamethrin 

in food handling establishments, including food service, manufacturing and 

processing establishments, such as restaurants, cafeterias, supermarkets, bakeries, 

breweries, dairies, meat slaughtering and packing plants, and canneries, feed 

handling establishments including feed manufacturing and processing 

establishments, in accordance with the following prescribed conditions:

Compliance with the tolerance levels specified 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-mphenoxybenzyl(1R,3S)-3-(2,2-dibromovinyl)-2,2-

dimethylcyclopropanecarboxylate, and alpha-R-deltamethrin, (R)-alpha-cyano-mphenoxybenzyl-(1R,3R)-3-(2,2-dibromovinyl)-2,2-

dimethylcyclopropanecarboxylate, in or on the commodity.

 

2.2.4 Revisions to Petitioned-For Tolerances

None

2.3 Label Recommendations

The proposed label contains the following statement: “Apply at a rate not to exceed 0.0014 

pounds of deltamethrin per acre in any given 24-hour period.” The adulticide residue trials were 

performed at a 3-day retreatment interval, however. As a result, the registrant should revise the 

label to state that the maximum single application rate is 0.00134 lb ai/A, and the minimum retreatment interval is 3 days.

The label also states: “Do not make more than 25 applications per site per year.” In the residue 

trials that were performed, only 10 applications were made. As a result, the registrant should 

revise the label to state that no more than 10 applications per year may be made at the maximum 

application rate of 0.00134 lb ai/A.
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The proposed label also states: “Do not exceed 0.036 pounds of AI per acre per year to any 

site.” This maximum value of 0.036 lb ai/A is based on 25 applications per year, rather than 10. 

As a result, the registrant should revise the label to state that 0.0134 lb ai/A is the maximum 

seasonal application rate.

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) BES0668 Insecticide (EPA File Symbol 432-RLGU) 

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

Bayer Environmental Science submitted a proposed label for the mosquito adulticide 

formulation, BES0668 Insecticide, a liquid containing 2.0% active ingredient. It may be applied 

by ULV truck mounted fogger and portable backpack or hand-carried equipment at a single 

maximum application rate of 0.00134 lb ai/acre in residential, industrial, urban, recreational, 

municipal, agricultural and other areas where adult mosquitoes and flies are found. BES0668 is 

also to be applied in indoor/outdoor livestock and poultry facilities. This product is to be applied 

by federal, state, tribal, or local government officials responsible for public health or vector 

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

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

O

O

H

O

Br

Br NC
Deltamethrin Human Health Risk Assessment DP No. D417556

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their direct supervision, or as allowed by state regulations for persons treating private property. 

BES0668 is also to be applied at a single maximum application rate of 0.0018 lb ai/acre for 

control of sand flies by the United States military by ULV ground applications. A summary of 

the proposed use pattern is presented in Table 3.3.a.

The proposed label contains the following statement: “Apply at a rate not to exceed 0.0014 

pounds of deltamethrin per acre in any given 24-hour period.” The adulticide residue trials were 

performed at a 3-day retreatment interval, however. As a result, the label should be revised to 

state that the maximum single application rate is 0.00134 lb ai/A and the minimum re-treatment 

interval is 3 days.

The label also states: “Do not make more than 25 applications per site per year.” In the 

submitted residue trials, only 10 applications were made. As a result, the registrant should revise 

the label to state that no more than 10 applications per year may be made at the maximum 

application rate of 0.00134 lb ai/A.

The proposed label also states: “Do not exceed 0.036 pounds of AI per acre per year to any 

site.” This maximum value of 0.036 lb ai/A is based on 25 applications per year, rather than 10. 

As a result, the registrant should revise the label to state that 0.0134 lb ai/A is the maximum 

seasonal application rate.

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 

Table 3.3.a. Summary of Directions for Proposed Mosquito Vector Control Use of Deltamethrin.

Method of 

Application

Product and 

Formulation

(Reg. No.)

Application 

Rate

(lb ai/A)

Maximum 

No. 

Applications 

per Season

Maximum 

Seasonal 

Application 

Rate

(lb ai/A)

RTI

(days)

Use Directions, 

Application Timing, 

Type and Limitations

Truck mounted 

ULV fogger, 

Ground, and 

Hand Held 

Equipment

BES0668 

Insecticide

Reg. No. 432-

RLGU

(0.17 lb ai/gal)

0.00134

lb ai/A

over crops

25

0.036 

lb ai/A in 

one year over 

crops

3

More frequent 

applications may be 

made to prevent or 

control a threat to 

public/animal health 

determined by a state, 

tribal or local health or 

vector control agency.

0.0018 

lb ai/A

20 0.036 lb ai/a 

per year

NA

To be applied by U.S. 

military personal under 

U.S. military 

supervision for control 

of sand flies
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paint additive products. For the purpose of updating the aggregate human health risk assessment, 

previously assessed representative residential uses have been re-evaluated using the 2012 

Residential SOPs. A more comprehensive assessment might be completed during registration 

review. A summary of the representative registered residential 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 application. Also 

treat 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 treatments 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 treatments are to 

be made as building 

perimeter treatments or 

broadcast to lawns, 

recreational grounds, and 

ornamentals.

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.
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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

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 nonresidential 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. There is also the potential for exposure to occupational 

applicators while handling the pesticide prior to application as well as during application. In 
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addition there is the potential for residential post-application exposure to the mosquito adulticide 

via the inhalation route. 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 post-application incidental oral exposure for children have been reassessed for 

the purpose of completing an aggregate risk assessment. Although there is the potential for 

dermal exposure, there is no dermal endpoint and, therefore, this exposure route has not been 

assessed.

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 

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).
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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 

-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). 

Target 

Tissue 

Dose

VGSC 

Alterations

In Vivo 

Clinical 

Signs

Altered 

Neuronal

Excitability
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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. No toxicity was 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 had no 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 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 PODs selected for risk assessment. Therefore, 

the current PODs are protective of the observed sensitivity.
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There was no evidence of immunotoxicity in an immunotoxicity study in rats or in any other 

study in the toxicology database. 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. 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 

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 
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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 

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 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.
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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 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.

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 
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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 

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 Safety 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, of 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 
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higher than the POD from 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 because 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.

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.
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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.

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. 
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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 

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. 
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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 was observed in animals of 

a similar life stage (PND 4 and PND 8-14, respectively) as the animals 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.

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 because of the 

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

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

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

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

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

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

4.5.1 Dose-Response and Hazard Assessment 

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, as well as shortterm 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 

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. 
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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 analyses, 

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, PBPK models are currently available for species extrapolation 

from rats to humans. The use of PBPK models to predict human equivalent concentrations is not 

necessary for the current action. 

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.

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 
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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).

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
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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

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

Occupational 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

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 
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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 

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 
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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 5.1.4. 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

Bayer conducted mosquito adulticide residue trials in accordance with a protocol that was 

previously approved by HED’s Chemistry Science Advisory Council (ChemSAC) and submitted 

a report of the results (MRID 49114112). Residue results are supported by adequate storage 

stability and analytical method data. Residues were below 0.05 ppm in all samples of leaf lettuce 

treated at both the 1x and 1⁄2x rate. In grass forage, residues ranged up to 0.087 ppm in samples 

treated at a 1x rate. In alfalfa forage, residues ranged up to 0.070 ppm in samples treated at a 1x 

rate. Residues in alfalfa hay and grass hay are not being considered for tolerance-setting 

purposes for crops because hay is a dried commodity. In all trials, residues increased with an 

increase in the number of treatments.

HED notes that the residue trials were conducted using grass, alfalfa, and lettuce as 

representative crops reflecting the potential for residues if crops are directly treated with the 

mosquito adulticide; however, in general, residential areas are the areas being intentionally 

treated, and the potential for drift onto growing crops is fairly low based on the Biological and 

Economic Analysis Division’s (BEAD) estimate of 1% crop treated for all crops for the 

mosquito adulticide use. Therefore, although there were some residues slightly above the 

recommended tolerance of 0.05 ppm, HED considers this tolerance to be protective of residues 

that will be found when the mosquito adulticide is used in accordance with the label 

recommendations (e.g., maximum single application rate, a maximum of 10 applications, and a 

3-day re-treatment interval).
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5.3 Water Residue Profile

EFED assessed the proposed adulticide use of deltamethrin (D417559, J. Melendez, 10/9/2014), 

and determined that the previous drinking water assessment, dated April 24, 2007 could be used 

to cover the proposed use because the surface water estimated drinking water concentrations 

(EDWCs) calculated for the adulticide use using the Surface Water Concentration Calculator 

(SWCC), were lower than the values previously determined (D335136, J. Melendez, 4/24/2007). 

Furthermore, the groundwater values are at the limit of solubility of 0.2 ppb. EFED determined 

that there was no need to conduct a PRZM-GW assessment. 

For the 2007 assessment, EFED calculated the EDWCs based on a maximum application rate of 

0.45 lb a.i./A/season. EFED determined the groundwater concentrations using the Screening 

Concentration in Groundwater (SCIGROW) Model and the surface water concentrations using 

the FQPA Index Reservoir Screening Tool (FIRST) Model. The acute drinking water 

concentration in surface water is 0.20 ppb. It was based on applications of the chemical to sweet 

corn. The cancer/chronic EDWC is 0.0771 ppb (based on applications to sweet corn, with the 

highest application rate). The 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.

Overall, because of the low estimate of 1% of all crops treated (PCT) for the wide-area mosquito

adulticide, as well as the low residue level of 0.05 ppm (i.e., the same as the food handling 

establishment tolerance), the dietary exposure estimates did not increase significantly compared 

to those recently provided in conjunction with the tolerance established for residues in fish 

(without a US registration).

5.4.1 Description of Residue Data Used in Dietary Assessment

The acute and chronic dietary exposure assessments are partially refined. In the acute 

assessment, residues could result from two different sources: agricultural uses and adulticide 

uses. In the chronic assessment, residues could result from three different sources: agricultural 

uses, FHE uses, and adulticide uses. In the assessments, residue inputs consisted of a 

combination of tolerance level residues, monitoring data, mosquito adulticide residue values, and 

FHE residue values. The residue input files included both plant and livestock commodities. 
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Detailed discussions of the residue values can be found in the dietary exposure memo prepared 

in support of this risk assessment (D423638, D. Dotson, 12/4/2014). Conservative inputs were 

used in both the acute and chronic assessments, including the assumption that drinking water 

residues would be present at the limit of solubility of deltamethrin. As a result, HED has not 

underestimated exposure. 

Acute Assessment

In the acute assessment, tolerance level residues were used for most commodities. Distributions 

of monitoring data were used for a number of commodities including carrots, carrot babyfood, 

soybeans, tomatoes, cantaloupes, watermelons, cucumbers, apples, apple juice, apple sauce 

babyfood, pears, pear babyfood, cereal grains, and milk. To account for the adulticide use, a 

distribution of the residue values from the adulticide trial was used. The residue values were 

modified by maximum %CT estimates provided by BEAD (for blended commodities) or were 

included in a distribution considering the %CT estimate. Additional information regarding %CT 

estimates is provided below. The data for the various commodities in the assessment were 

entered into the residue input file as indicated in Table 5.4.1.a. That is, if the commodity would 

only have a residue as a result of the adulticide use, then an adulticide residue value was used; 

however if the commodity could have residues from both agricultural uses and the adulticide, 

this possibility was addressed in the analysis. Essentially, for the situation in which residues 

could occur from both sources, the DEEM Model sampled the agricultural distribution 99% of 

the time, and the adulticide distribution only 1% of the time. The limit of solubility of 

deltamethrin in water was used as a point estimate for drinking water. DEEM-FCID Version 

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

were used for others.

Table 5.4.1.a. Summary of Treatment of Data Used in Acute Assessment.

Type of 

Commodity

Established 

Tolerance/No 

Tolerance

Tolerance/PDP 

Used

Blending 

Classification

Data Used

Plant Tolerance Tolerance - Tol + Mosq

Plant Tolerance PDP NB/PB PDP + Mosq

Plant Tolerance PDP Blended Avg PDP + Mosq

Plant Tolerance PDP for RAC Blended Avg PDP for RAC based on 

Max %CT + Mosq

Plant No Tolerance - - Mosq

Livestock Tolerance Tolerance - Tol

Livestock

(Milk Only)

No Tolerance PDP - PDP

Chronic Assessment

In the chronic assessment, tolerance level residues were used for most commodities. The 

average PDP value was used for cereal grains and milk. The average mosquito adulticide residue 

value was used to account for the adulticide uses and 1⁄2 the FHE tolerance was used to account 

for the FHE uses. The residue values were modified by %CT estimates provided by BEAD, as 

discussed in the %CT information section below. The data for the various commodities in the 
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assessment were entered into the residue input file using the approach described in Table 5.4.1.b. 

The limit of solubility in water for deltamethrin was used in the dietary assessment. This value is 

considered to be conservative. DEEM-FCID Version 7.81 default processing factors were used 

for some processed commodities and empirical factors were used for others.

Table 5.4.1.b. Summary of Treatment of Data Used in Chronic Assessment.

Type of 

Commodity

Established 

Tolerance/No 

Tolerance

Tolerance/PDP 

Used

%CT 

Estimate Used

Data Used

Plant Tolerance Tolerance 100% Tol + Mosq

Plant Tolerance Tolerance Estimate (Tol x %CT) + Mosq.

Plant Tolerance PDP - Avg PDP + Mosq

Plant No Tolerance - - FHE + Mosq

Livestock Tolerance Tolerance - Tolerance

Livestock

(Milk Only)

Tolerance PDP - Avg PDP

Livestock No Tolerance - - FHE + Mosq

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

As noted above, in the acute and chronic assessments, the mosquito adulticide %CT estimate of 

1% was used. Residues from the adulticide use were included for all commodities with the 

exception of livestock commodities. Additional %CT information is as follows:

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

Crops with an assumption of 4.65% CT (i.e., with residues resulting only from the FHE use): 

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 

general U.S. population is 18% of the aPAD. The population subgroup with the highest acute 

dietary risk estimate is Children 3-5 years old, which uses 81% 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. The dietary assessment is conservative, even though monitoring

data were used, because it is based on the use of (1) some tolerance level data, (2) a conservative 

approach to estimating residues that could result from FHE uses, (3) the use of upper bound 

%CT estimates, and (4) the limit of solubility as an estimate of deltamethrin residues in drinking 

water. 

The acute dietary exposure estimates increased slightly for all population subgroups as a result of 

the inclusion of residues from the adulticide applications. Residues in the adulticide trials were 

low and the %CT estimate was also low (1%). For these reasons, the results demonstrated that 

the use of deltamethrin as a mosquito adulticide will make an insignificant contribution to the 

acute dietary risk associated with the chemical.

5.4.4 Chronic Dietary Exposure Assessment

The chronic dietary exposure estimate for the general U.S. population is 0.000259 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 0.000846 mg/kg/day.

As with the acute dietary exposure estimates, the chronic dietary exposure estimates increased 

slightly for all population subgroups as a result of the inclusion of residues from the adulticide 

applications. Again, the results demonstrated that the use of deltamethrin as a mosquito 

adulticide will make an insignificant contribution to the dietary risk associated with the chemical.
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5.4.5 Summary Table

Table 5.4.5. Summary of the Acute and Chronic Dietary 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 0.002614 18 NA 0.000259

NA

All infants 0.005 0.003421 68 NA 0.000308

Children 1-2 yrs* 0.005 0.004071 81 NA 0.000846

Children 3-5 yrs 0.005 0.003998 80 NA 0.000618

Children 6-12 yrs 0.0149 0.002372 16 NA 0.000386

Youth 13-19 yrs 0.0149 0.001701 11 NA 0.000211

Adults 20-49 yrs 0.0149 0.002210 15 NA 0.000198

Adults 50-99 yrs 0.0149 0.001719 12 NA 0.000214

Females 13-49 yrs 0.0149 0.002669 18 NA 0.000195

*Most highly exposed population subgroups

6.0 Residential Exposure and Risk Estimates

There are no residential handler exposure scenarios associated with the proposed mosquito 

control use as applications are to be made by federal, state, tribal or local government officials as 

well as the U.S. military. However, there is potential for residential post-application exposure 

associated with the proposed wide-area mosquito and fly control use. This document provides 

residential handler and post-application exposure assessments for existing residential indoor, 

outdoor, pet, and paint preservative uses for the purpose of updating the aggregate human health 

risk assessment. This assessment reflects updates to HED’s 2012 Residential SOPs1, 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.

6.1. Proposed Use: Wide-Area Mosquito Control

There are residential post-application exposure scenarios associated with the proposed mosquito 

and fly control use, as applications are to be made in residential, urban, recreational, and other 

areas where adult mosquitoes and flies are found. Since the proposed label did not specify where 

the military would be applying this product for control of sand flies, all post-application risk 

estimates were based on the highest application rate of 0.0018 lb ai/acre to be protective of all 

potential scenarios for adults and children.

To calculate post-application exposure from ULV truck fogger applications, HED used the 2012 

Residential SOPs for Outdoor Fogging/Misting Systems, with minimal modification to the wellmixed box (WMB) model. The WMB model allows for the estimation of inhalation exposure in 

the breathing zones of adults and children residing in areas being treated by ground application 

 

1 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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of deltamethrin. This methodology is a modification of the previous method used in assessing 

post-application inhalation exposure resulting from a truck mounted mosquito fogger. The 

revised methodology more accurately accounts for dilution using the WMB model. The 

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

scenarios: 

 Post-application inhalation exposure resulting from ULV truck fogger mosquito and fly 

applications, and,

 Incidental oral (hand-to-mouth) contact with residues deposited on lawn/turf resulting 

from liquid formulations from ULV truck fogger mosquito and fly applications.

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

Appendix in the 2012 Residential SOPs2. The assessment of the lifestages provided in this 

document is protective for the exposure and risk estimates of all other lifestages with potential 

exposure.

The data and assumptions, as well as detailed algorithms/calculations used to derive postapplication exposure from use of a truck fogger are described in detail in the occupational and 

residential exposure assessment for the proposed mosquito adulticide use (D417525, M. 

Collantes, 12/18/2014).

All post-application inhalation and incidental oral exposure estimates for the mosquito control 

scenarios resulted in MOEs greater than their respective LOCs and are not of concern. Table 

6.1.a provides a summary of the post-application inhalation risk estimates and Table 6.1.b 

provides a summary of the incidental oral risk estimates resulting from ground (truck fogger) 

applications of deltamethrin.

Table 6.1.a. Post-application Inhalation Exposure & Risk Estimates from Wide-area Mosquito 

Adulticide Use.

Life Stage Application 

Rate1

Inhalation 

Rate2

(m3/hr)

Q3

(m3/hr)

Exposure4

(mg/day)

Dose5

(mg/kg/day)

Inhalation 

MOE6

Adult 7.5

mg ai/day

0.64 5400 0.00089 0.000011 130,000

Child 0.33 0.00046 0.0000417 36,000

1. Application Rate scaled to WMB (see Appendix E of M. Collantes, D417525) = (0.0018 lb ai/A x 454 g/lb 

x 1000mg/g)/(43,560 ft2/400 ft2) = 7.5 mg ai/day.

2. Inhalation Rate = Residential SOPs.

3. Q = Airflow through treated area (5400 m3/hr).

4. Exposure (mg/day) = AR (mg ai/day) x IR (m3/hr)/ Q (m3/hr).

5. Inhalation Dose (mg/kg/day) = Exposure (mg/day)/BW (kg). 

 6. Inhalation MOE = BMDL (1.49 mg/kg/day) /Inhalation Dose (mg/kg/day); Adults and children > 6 yrs 

LOC = 100; Children < 6 yrs LOC = 300.

 

2 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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Table 6.1.b. Incidental Oral Exposure Estimates Resulting from BES0668 Insecticide.

Use/Scenario Application Rate

(lb ai/A)

Hand Residuea

(mg/ m2)

Incidental Oral 

Dose b 

(mg/kg/day)

Incidental 

Oral MOEc

Truck mounted ULV fogger, 

Ground and Hand Held 

Equipment

0.0018 0.0000001 0.000001 2,700,000

a. Hand Residue = 

SA * 2

Fai *DE

HR

H

hands



(See Appendix B of M. Collantes, D417525).

b. Incidental Oral Dose (mg/kg/day) = [HR * (FM * SAH) * (ET * N_Replen) * (1- (1- SE)

(Freq_HtM/N-Replen))].

c. Incidental Oral MOE = NOAEL (1.49 mg/kg/day)/Incidental Oral Dose (mg/kg/day) ; LOC = MOE ≥ 300.

6.2 Residential Handler Exposure/Risk Estimates for Registered Uses

A residential handler exposure assessment was previously performed for existing residential 

indoor, outdoor, turf, pet, and paint uses (D418867, M. Collantes, 6/11/2014), and the resulting 

scenarios and MOEs are still considered appropriate for the purpose of conducting an aggregate 

risk assessment.

Summary of Registered Residential Handler Exposure and Risk Estimates

Representative (worst case) registered residential uses were previously assessed using the 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 lowest MOE of 4,300 was associated with the use of a backpack sprayer to treat lawns with 

a wettable powder formulation. The exposure estimates are summarized for the worst-case 

representative residential handler exposure scenario for each registered product in Table 6.2.

Table 6.2. 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
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Table 6.2. 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

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

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 one gal cans 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 pets NA

1 Based on registered labels.

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

3 Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate × 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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6.3 Residential Post-application Exposure/Risk Estimates for Registered Uses

A residential post-application exposure assessment was previously performed for existing 

residential indoor, outdoor, lawn, pet, and paint uses (D418867, M. Collantes, 6/11/2014). Risk 

estimates for these registered residential scenarios have been revised to reflect updates to HED’s 

2012 Residential SOPs3, along with policy changes for body weight assumptions and updated 

toxicological endpoints. 

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

Systemic toxicity via the dermal route of exposure is not anticipated. No treatment-related 

findings were observed at the limit dose; therefore, a dermal point of departure (POD) was not 

selected and a post-application dermal exposure assessment is not required. Furthermore, postapplication inhalation exposure for adults and children is anticipated to be negligible for 

representative residential registered uses; therefore, a quantitative post-application inhalation 

exposure assessment was not performed. All the representative indoor/outdoor and pet 

incidental oral (hand-to-mouth) post-application scenarios resulted in risk estimates ranging from 

an MOE of 630 (for incidental oral exposure following treatment of mattresses for bedbugs) 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 6.3.

Table 6.3. 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

 

3 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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Table 6.3. 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

Episodic 

Ingestion 0.0127 120

Adult

Lawn/Turf 

K-Othrine SC 

Insecticide

Reg. No.432-763

(0.06% ai)

(using default TTR 

value)

Dermal

0.13 lb ai/A

NA NA Inhalation

Child

Dermal NA NA

Inhalation

HTM 0.0020 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 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).

4. HTM = Hand-to-Mouth ; OTM = Object-to-Mouth

Turf Transferable Residue (TTR) Data

The estimated residential turf post-application exposure using the default TTR value for

deltamethrin is not minimal in comparison to the level of concern (i.e., the calculated MOE is not

greater than 10 times the level of concern, MOE = 750 compared to the LOC of 300). 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 TTR data 

in accordance with 40CFR Part 158 to facilitate any necessary exposure assessment refinements

and to further EPA’s general understanding of the availability of turf transferable pesticide 

residues.

Episodic Granular Ingestion

The default granular ingestion rate of 0.3 grams/day was adjusted to 0.14 grams/day (1/10 of the 

product) to reflect the amount of product applied on a per area basis (3 lb/1000ft2) as explained 

in the Residential SOP for Turf and Lawns. The reduction in ingestion rate resulted in an 

estimated dose of 0.0127 mg/kg/day and an MOE of 120, which is below the LOC for incidental
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ingestion of granules. In order to achieve an MOE greater than the LOC (MOE ≥ 300) based on 

amount of product applied per area, the application rate would need to be reduced from the 

current rate of 0.000003 lb ai/ft2to 0.000001 lb ai/ft2. However, 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, 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. 

6.4 Residential Risk Estimates for Use in Aggregate Assessment

The recommended residential exposure for the 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 resulting from control of bed bugs 

scenario was selected to estimate aggregate exposure for children. This scenario resulted in an

MOE of 630 and is not of concern. A summary of the residential risk estimates for use in the 

aggregate assessment is provided in Table 6.4.

Table 6.4. Recommendation for the Residential Exposure to be Used in the Deltamethrin 

Aggregate Assessment.

Lifestage Exposure 

Scenario

Dose (mg/kg/day)1 MOE2

Dermal Inhalation Oral Total Dermal Inhalation Oral Total

Adult 

Male

Back Pack 

– Garden 

and Trees NA

0.00034 N/A NA NA 4,300 N/A NA

Child

Bed Bug 

Scenario 

(Indoor)

NA 0.0023 NA NA NA 630 NA

1 Dose = the highest dose for each applicable lifestage of all residential scenarios assessed. Total = dermal + inhalation + incidental oral (where 

applicable).

2 MOE = the MOEs associated with the highest residential doses. Total = 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE) + (1/Incidental Oral 

MOE), where applicable.

6.5 Spray Drift

Spray drift is a potential source of exposure to those nearby pesticide applications. This is 

particularly the case with aerial application, but, to a lesser extent, spray drift can also be a 

potential source of exposure from the ground application methods (e.g., groundboom 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 
Deltamethrin Human Health Risk Assessment DP No. D417556

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Drift website for more information)4. 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. 

This product may be applied over any and all crops or agricultural areas, (including row, tree, 

fruit, citrus, pasture, rangeland, and other areas where agricultural enterprises take place) for the 

control of adult mosquitoes within or adjacent to the treatment areas, or to areas where drift over 

cropland could occur. 

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.

7.1 Acute Aggregate Risk

Acute aggregate risk for 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 

 

4 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htm 
Deltamethrin Human Health Risk Assessment DP No. D417556

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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.

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 0.000259 0.00034 0.000599 2,500

Females 13-49 1.49 100 0.0149 0.000195 0.00034 0.000535 2,800

Children 1-2 1.49 300 0.005 0.000846 0.002 0.002822 520

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 

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 use of deltamethrin as a mosquito adulticide has an insignificant impact on the CRA. 

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 wide-area mosquito adulticide use 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.
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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 risk 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 risks 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 uses 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 wide-area mosquito 

adulticide use 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

9.1 Occupational Handler Exposure/Risk Estimates

Based on the anticipated use patterns and current labeling, types of equipment, and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following scenarios: 

 Mixer/loader ULV mosquito and fly control via groundboom (surrogate for truck 

mounted fogger) for residential, agricultural, industrial, poultry and livestock facilities, 

 Mixer/loader ULV mosquito and fly control via airblast (surrogate for truck mounted 

fogger), for residential, agricultural, industrial, poultry and livestock facilities, and

 Applying ULV mosquito and fly control via airblast (surrogate for truck mounted fogger) 

for residential, agricultural, industrial, poultry and livestock facilities.
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Summary of Occupational Handler Exposure and Risk Estimates

Occupational handler scenarios associated with truck mounted fogger applications resulted in 

inhalation MOEs greater than the LOC (inhalation MOE ≥ 100) at baseline (single layer 

clothing, no gloves or respirator) and are not of concern. A summary of the occupational handler 

risk estimates is provided in Table 9.1. 

 Table 9.1. Occupational Handler Exposure Risk Estimates for Deltamethrin.

Exposure 

Scenario

Crop or 

Target

Inhalation Unit 

Exposure

(μg/lb ai)1

Maximum 

Application Rate2

(lb ai/A)

Area 

Treated or 

Amount 

Handled 

Daily3

Inhalation

Mitigation 

Level

Dose 

(mg/kg/day)4 MOE5

Mixer/Loader

Airlbast (surrogate 

for Truck Mounted 

Ground fogger)

Mosquito and 

Fly Control in 

Residential, 

Industrial and 

Agricultural 

Areas

0.219

Baseline 0.0018

3,000 A

Groundboom 0.0000148 100,000

(surrogate for Truck 

Mounted Ground 

fogger)

Airblast(surrogate 

for Truck Mounted 

Ground fogger) Poultry and 

Livestock 

Facilities

0.219

Baseline Groundboom 0.00134 0.000011 140,000

(surrogate for Truck 

Mounted Ground 

fogger)

Applicator

Airblast (surrogate 

for Truck Mounted 

Ground fogger)

Mosquito and 

Fly Control in 

Residential, 

Industrial and 

Agricultural 

Areas

4.71 Baseline 0.0018

3,000 A

0.000318 4,700

Groundboom 

(surrogate for Truck 

Mounted Ground 

fogger) Poultry and 

Livestock 

Facilities

0.34

Baseline

0.00134

0.000017 87,000

Airblast

(surrogate for Truck 

Mounted Ground 

fogger)

4.71

Baseline 0.000236 6,300

Mixer/Loader/Applicator

Manually 

Pressurized 

Handwand Poultry and 

Livestock 

Facility

30

0.000045

lb ai/gal

40 gals 0.00000067 2,200,000

Mechanically 

Pressurized 

Handwand

3.9 1,000 gals 0.0000022 680,000

1 Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”; Level of mitigation: Baseline, PPE, 

Engineering Controls.

2 Based on the proposed use.

3 Exposure Science Advisory Council Policy #9.1.
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4 Inhalation Dose = Inhalation Unit Exposures (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (0.0018 lb 

ai/acre) × Area Treated or Amount Handled (A) ÷ BW (80 kg).

5 Inhalation MOE = Inhalation BMDL (1.49 mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

9.2 Occupational Post-application Risk Estimates

9.2.1 Occupational Post-application Inhalation Risk Estimates

There are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated fields. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 

pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel 

(SAP) in December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.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-HQOPP-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 are

required for deltamethrin. In addition, the Agency is continuing to evaluate the available postapplication inhalation exposure data generated by the Agricultural Reentry Task Force. Given 

these two efforts, the Agency will continue to identify the need for and, subsequently, the way to 

incorporate occupational post-application inhalation exposure into the Agency’s risk 

assessments.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational handlers. 

Handler exposure resulting from application of pesticides outdoors is likely to result in higher 

exposure than post-application exposure. Therefore, it is expected that these handler inhalation 

exposure estimates would be protective of most occupational post-application inhalation 

exposure scenarios.

9.2.2 Occupational Post-application Dermal Risk Estimates

Systemic toxicity via the dermal route of exposure is not anticipated. No treatment-related 

findings were observed at the limit dose; therefore, a quantitative dermal exposure assessment is 

not required.

10.0 References

D423045, Deltamethrin. Petition for the Proposed Use of the Insecticide as a Mosquito 

Adulticide. Summary of Analytical Chemistry and Residue Data, 12/4/2014
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MRID 49114112. M. Krolski (2013) Magnitude of the Residue in/on Alfalfa, Leaf Lettuce, and 

Grass Following Ultra Low Volume (ULV) Spray for Mosquito Control. Study Number: 

RADAN008. Unpublished study prepared by Bayer CropScience. 788 pages

D423638, Deltamethrin. Acute and Chronic Aggregate Dietary (Food and Drinking Water) 

Exposure and Risk Assessment for the Proposed Use of Deltamethrin as a Wide-area Mosquito 

Adulticide over Agricultural Crops, D. Dotson, 12/4/2014

D417525, Occupational and Residential Exposure Assessment for Proposed Area Wide 

Mosquito and Fly Control, M. Collantes, 12/18/2014

D417559, Tiers I and II Estimated Drinking Waters Concentrations for Deltamethrin for the New 

Use as an Adulticide for the Product BES0668 Insecticide, J. Melendez, 10/9/2014

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”

Environmental Health Perspectives

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.”

Toxicology and Applied Pharmacology 211(3): 233-244

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.” Neurotox Teratol 17(4) 489

Godin, S. J., M. J. DeVito, M. F. Hughes, D. G. Ross, E. J. Scollon, J. M. Starr, R. W. Setzer, R. 

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
Deltamethrin Human Health Risk Assessment DP No. D417556

Page 48 of 67

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

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
Deltamethrin Human Health Risk Assessment DP No. D417556

Page 49 of 67

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

Weiner, M. L., M. Nemec, L. Sheets, D. Sargent and C. Breckenridge (2009). “Comparative 

functional observational battery study of twelve commercial pyrethroid insecticides in male rats 

following acute oral exposure.” Neurotoxicology 30 Suppl 1: S1-16

Wolansky, M., C. Gennings and K. Crofton (2006). “Relative potencies for acute effects of 

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 

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 A.2. Toxicity Profile Tables

Table A.2.1 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 A.2.2 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 A.2.2 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 A.2.2 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 A.2.2 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 A.2.2 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 A.2.2 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.