UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: May 22, 2014 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Chlorfenapyr- Preliminary Human Health Risk Assessment for Registration 

Review 

PC Code: 129093 

Decision No.: 485596 

Petition No.: NA 

DP Barcode: 0416560 

Registration No.: N/A 

Regulatory Action: Registration Review Risk Assessment 

Risk Assessment Type: Single Chemical/Aggregate Case No.: 7419 

TXRNo.: NA CAS No.: 122453-73-0 

MRID No.: NA 40 CFR: §180.513 

FROM: Monique M. Perron, S.D., Toxicologist 

William D. Wassell, Chemist 

Lata Venkateshwara, Environmental Scientist 

Risk Assessment Branch 1 (RAB 1) 

Health Effects Division (HED; 7509P) 

THROUGH: Charles 

George F. 

W. 

Kramer, 

Smith III

Ph.D., 

, Branch 

Senior 

Chief 

Chemist 

c::~~ --·-=--- ( ~ 

RAB 1/HED (7509P) 

And 

Ray 

Barry 

Kent, 

O'Keefe, 

Review 

Reviewer 

':S 

B. {) ~ t 

Risk Assessment Review Committee ( C) 

HED (7509P) 

TO: Margaret Hathaway 

Kevin Costello 

Pesticide Re-evaluation Division (PRD; 7508P) 

This document provides the HED's human health risk assessment for the Registration Review of 

chlorfenapyr ( 4-bromo-2-( 4-chlorophenyl)-1-ethoxymethyl-5-trifluoromethyl-1 H-pyrrole-3-

carbonitrile). The hazard characterization, endpoint selection, and risk assessment were provided 

by Monique Perron (RAB 1 ); the residue chemistry and dietary exposure assessments were 

provided by William Wassell (RAB 1 ); and the occupational and residential exposure assessment 

by Lata Venkateshwara (RAB 1 ). 

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Chlorfenapyr Preliminary Human Health Risk Assessment 0416560 

Table of Contents 

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

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

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

2.2 Tolerance Considerations ......................................................................... .... .... ........ ... ... 7 

2.2.1 Enforcement Analytical Method ..... ........... ............................................................. 7 

2.2.2 Tolerance Recommendations ..................................... ........... .... ................... ........ .... 8 

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

2.3 Label Recommendations ................................................................. .... ................ ............ 8 

3.0 Introduction .. .. ........... .............. ....... .... .... ....... .... ....... .... .... ....... .... .... ........................... ......... 9 

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

3.2 PhysicaUChemical Characteristics ....... ...................... ................... ... .. .. .... .... .... ............ I 0 

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

3.4 Anticipated Exposure Pathways ................................................................................... 14 

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

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

4.1 Toxicology Studies Available for Analysis ..................................... .... ... .... .... ..... ........ . 14 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME) ............ .................. 15 

4.2.1 Dermal Absorption ........................................................................................ ......... 15 

4.3 Summary of Toxicological Effects .................................................................. .............. 15 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) .... ....................... ...... 17 

4.4.1 Completeness of the Toxicology Database ............................................................. 17 

4.4.2 Evidence of Neurotoxicity ......................................... .... ............................ ............ .. 17 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal ...... 17 

4.4.4 Residual Uncertainty in the Exposure Database ..... ....... .... .... ........ ...................... 17 

4.5 Toxicity Endpoint and Point of Departure Selections ............................. .... ........ ....... 17 

4.5.1 Recommendation for Combining Routes of Exposures for Risk Assessment ... 19 

4.5.2 Cancer Classification and Risk Assessment Recommendation .......................... 19 

4.5.3 Summary of Points of Departure and Toxicity Endpoints Used in Human 

Health Risk Assessment ..................... .............................. .... .... ........................................... 19 

4.6 Endocrine Disruptor Screening Program ................................................................ 21 

5.0 Dietary Exposure and Risk Assessment.. ...... ........... .... ... .... ........... ................................. 22 

5.1 Residues of Concern Summary and Rationale ......................................... .... .... .... .... .. 22 

5.2 Food Residue Profile ....................... .... ... ........ ....... .... ........... ......................................... 23 

5.3 Water Residue Profile .................. · ............................................... .... ........... ..... .... ... ....... 23 

5.4 Dietary Ri&k Assessment ......... ................................................................................... ... 24 

5.4.1 Description of Residue Data Used in Dietary Assessment .... .............................. 24 

5.4.2 Acute Dietary Risk Assessment .. .... ........................................................ .... .... .... ... 24 

5.4.3 Chronic Dietary Risk Assessment ......................................................................... 24 

5.4.4 Cancer Dietary Risk Assessment.. ....................................... ........ .......................... 25 

5.4.5 Summary Table .......................................................... ............................................. 25 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............... .... .... .... ... 25 

6.1 Residential Handler Exposure .... : .............................................. .... .... ........................... 25 

6.2 Post-Application Exposure .............................. ......................................................... .... 25 

6.2.1 Post-application Inhalation Exposure and Risk Estimates ................................. 26 

6.2.2 Post-application Dermal Exposure and Risk Estimates ...................... .... .... .... .... 27 

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Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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6.2.3 Post-application Incidental Oral Exposure and Risk Estimates ........................ 28

6.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios).................... 30

6.4 Residential Risk Estimates for Use in Aggregate Assessment................................... 31

6.5 Spray Drift...................................................................................................................... 31

7.0 Aggregate Exposure/Risk Characterization................................................................... 32

8.0 Cumulative Exposure/Risk Characterization ................................................................ 33

9.0 Occupational Exposure/Risk Characterization ............................................................. 33

9.1 Short- and Intermediate-Term Handler Risk............................................................. 33

9.2 Occupational Post-Application Exposure ................................................................... 37

10.0 References....................................................................................................................... 39

Appendix A. Toxicology Profile................................................................................................ 39

A.1 Toxicology Data Requirements................................................................................. 40

A.2 Toxicity Profiles.......................................................................................................... 41

Appendix B. Physical/Chemical Properties............................................................................. 45

Appendix C: Summary of Occupational and Residential Algorithms.................................. 46

Appendix D. Registered Chlorfenapyr End-Use Products .................................................... 55

Appendix E. Review of Human Research................................................................................ 56
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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1.0 Executive Summary

Background: Chlorfenapyr is a member of the pyrroles class of insecticide/miticides. The 

parent compound is converted to the N-dealkylated metabolite in the organism. The pesticidal 

mode of action of this active form functions as an uncoupler of oxidative phosphorylation in 

mitochondria, which disrupts ATP production leading to cell dysfunction and subsequent death 

of the organism. Chlorfenapyr is registered for application to fruiting vegetables and 

ornamentals (greenhouse only) and crack/crevice/spot treatment on indoor and outdoor 

residential sites (including as a bed bug treatment), food/feed handling areas, indoor and outdoor 

commercial sites (including sewers), and indoor medical sites. It is currently formulated into 

soluble-concentrate (SC), emulsifiable-concentrate (EC), and pressurized release liquid end-use 

products (e.g., total release foggers and aerosol cans) containing between 0.05% to 21.45% ai. 

Permanent tolerances (40 CFR §180.513) are established for residues of chlorfenapyr in/on the 

vegetables, fruiting, group 8 at 1.0 ppm and in/on all food commodities at 0.01 ppm. The most 

recent risk assessment for chlorfenapyr was completed in 2003 (G. Kramer, et al., 10-MAR2003; D275052). 

This preliminary risk assessment (PRA) provides information to support the Registration Review 

of chlorfenapyr and addresses the exposures and risk estimates associated with all currently 

registered uses. This document incorporates changes made due to submission of new data and 

updated HED policies. All data requirements identified during the scoping process have been 

satisfied (A. Dunbar; 26-MAY-2010; D373133).

Hazard Assessment: Chlorfenapyr targets the central nervous system (CNS), inducing 

neurohistological changes (spongiform myelinopathy of the brain and spinal cord and 

vacuolization of the brain, spinal cord, and optic nerve) from subchronic and chronic dietary 

administration in mice and rats. In addition to neuropathology, rats also exhibited 

neurobehavioral changes on the day of dosing in the acute neurotoxicity study. Decreased motor 

activity was observed in the acute neurotoxicity study as well as in offspring in the 

developmental neurotoxicity (DNT) study. Several rat studies also noted effects in the liver

(increased organ weights and tumors) at doses similar to or above those where CNS effects were 

seen. The liver was identified in metabolism studies as the single organ to have the highest 

recovery of administered dose. 

There was evidence of increased quantitative susceptibility to offspring in the database as a result 

of chlorfenapyr exposure. In the two-generation reproduction study, decreased pup weights were 

seen at the mid-dose with early pup deaths considered adverse at the highest dose tested (HDT). 

Parental toxicity (decreased body-weight) was only seen at the HDT. In the DNT study, 

offspring toxicity (decreased motor activity and increased pup deaths on postnatal days 1-4) was 

seen in the absence of maternal toxicity. Additional effects on the CNS (vacuolation of white 

matter in the brain and decreased hippocampus size) were also observed in offspring at the HDT

in this study. There was no evidence of increased susceptibility to offspring in the 

developmental studies. In both the rat and rabbit developmental toxicity studies, although no 

maternal or developmental effects were noted up to the HDTs, maternal observations are limited 

in these developmental studies. Consequently, the data from the DNT are considered more 

robust for assessing the effects of chlorfenapyr on the nervous system. 
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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Given the lack of toxicity in the rat and rabbit developmental studies, the early pup deaths in the 

reproduction toxicity and DNT studies are suspected to be the result of postnatal exposure 

through lactation. Chlorfenapyr has a relatively high octanol-water partition coefficient (logKOW

= 4.83) and has been shown to accumulate in milk due to its lipophilic nature in a dietary cow 

study. Additionally, in a rat metabolism study, chlorfenapyr was found to accumulate in the fat, 

such that females exhibited greater accumulation than males. This suggests chlorfenapyr is 

capable of accumulating in breast milk and likely causing the early pup deaths seen in the 

reproduction toxicity and DNT studies through lactation.

Chlorfenapyr is classified as having moderate acute toxicity via the oral route (Toxicity Category 

II) and low acute toxicity via the dermal and inhalation routes of exposure (Toxicity Category 

III). It is a mild eye irritant, but it is not a dermal irritant or sensitizer. 

Chlorfenapyr did not show any evidence of mutagenicity in in vitro or in vivo studies. 

Chlorfenapyr is classified as “suggestive evidence of carcinogenicity, but not sufficient to assess 

human carcinogenic potential.”

The chlorfenapyr risk assessment team recommends that the 10X Food Quality Protection Act 

Safety Factor (FQPA SF) be reduced to 1X for all exposure scenarios. The exposure databases 

are sufficient to determine the nature/magnitude of the residue in food and dietary exposure 

analyses are unlikely to underestimate risk of exposure from chlorfenapyr. Although there is 

evidence of neurotoxicity and susceptibility/sensitivity to offspring in the database, the effects 

are well-characterized with clearly established no observed adverse effect level (NOAEL)/lowest 

observed adverse effect level (LOAEL) values and selected endpoints are protective for the 

observed effects.

Dietary Risk Estimates: Unrefined acute and chronic dietary analyses were conducted using 

tolerance-level residues and 100% crop treated (CT). As most tolerances for chlorfenapyr are for 

uses in food/feed handling establishments and residues are expected to be incurred after 

processing, DEEM (ver. 7.81) processing factors were set to 1 for all commodities except 

tomato. Registered uses of chlorfenapyr on fruiting vegetables are for applications to greenhouse 

grown commodities. Greenhouse grown tomatoes are not typically considered to be processed; 

however, there is potential for imported tomatoes that have been treated with chlorfenapyr to be 

processed. As a result, default processing factors for tomato juice (1.5X), paste (5.4X), puree 

(3.3X), and dried (14.3X) were used in dietary analyses to account for imported tomato 

commodities. The analyses did not include exposure from drinking water as contamination of 

drinking water with chlorfenapyr is not expected to occur based on the use pattern.

There are no dietary risk estimates of concern. The acute dietary exposure is estimated at 14% of 

the acute population-adjusted dose (aPAD) for the general U.S. population and 35% of the aPAD

for children 3 to 5 years old, the population subgroup with the highest estimated acute dietary 

exposure to chlorfenapyr. The chronic dietary exposure is estimated at 3.8% of the chronic 

population-adjusted dose (cPAD) for the general U.S. population and 9.4% of the cPAD for 

children 1 to 2 years old, the population subgroup with the highest estimated chronic dietary 

exposure to chlorfenapyr.
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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Residential Risk: There are no registered or proposed residential handler uses of chlorfenapyr; 

therefore a residential handler exposure assessment was not conducted. There is potential for 

residential post-application exposure resulting from the currently registered uses of chlorfenapyr. 

The residential post-application exposure assessment yielded margins of exposure (MOEs) that 

are not of concern to HED (MOEs ≥ 100) for all scenarios except the combined (incidental oral, 

dermal, and inhalation) MOE for children (1 to <2 years old) with coarse-stream applications

(MOE=62). However, use of equipment with a pin stream nozzle results in a combined MOE for 

children (1 to <2 years old) that is above the level of concern (LOC). 

Aggregate Risk: Acute and chronic aggregate risk estimates are based solely on dietary sources

of exposure; therefore, the exposure estimates provided in the dietary exposure analysis represent 

acute and chronic aggregate exposure and are not of concern. Short- and intermediate-term 

aggregate risk assessments were performed since there is potential for post-application exposure 

from the uses of chlorfenapyr in residential settings. Since the short- and intermediate-term 

endpoints and points of departure (PODs) are the same, the short-term aggregate assessment is 

protective of intermediate-term exposure. The short-term aggregate MOE for adults is greater 

than the LOC and is therefore not a concern. For children (1 to <2 years old), the short-term 

aggregate exposure with coarse-stream applications yields an aggregate MOE less than the LOC

(MOE = 60). However, use of equipment with a pin-stream nozzle results in an aggregate MOE 

for children (1 to <2 years old) that is above the LOC. Chlorfenapyr is classified as “suggestive 

evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential”; 

therefore, a quantitative cancer aggregate risk assessment was not performed. 

Occupational Risk: For chlorfenapyr, based on the currently existing labeled use patterns, shortand intermediate-term occupational exposures are expected. Most occupational handler risk 

estimates resulted in MOEs greater than the LOC at baseline or label specified personal 

protective equipment (PPE), and therefore, are not of concern. However, there were several 

exposure scenarios that required additional PPE (some beyond what is currently on the registered 

labels) to reach MOEs greater than the LOC. For mixers/loaders/applicators of liquids using a 

mechanically-pressurized handgun for greenhouse applications, there are risks of concern 

(MOEs = 15-26) even with maximum PPE (i.e., double layer, gloves and PF10 respirator). 

An occupational post-application assessment was conducted for workers entering greenhouses 

after treatment of crops and/or ornamentals to perform various activities. Risk estimates for all

activities were not of concern (MOEs ≥ 100). The restricted-entry interval (REI) of 12 hours is 

adequate based on the acute toxicity of the active ingredient. 

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://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf.
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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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. Please refer to Appendix E for a discussion of 

the human study data used in this risk assessment. 

2.0 HED Recommendations

During the conduct of the chlorfenapyr PRA, HED identified a number of data deficiencies, 

tolerance considerations, and label recommendations, which are outlined in the sections below.

2.1 Data Deficiencies

 In accordance with 40 CFR Part 158, dislodgeable foliar residue (DFR) data are required 

for all occupational or residential uses that could result in post-application exposure to 

foliage. As part of the recent revision to the Health Effects Division’s 2012 Standard 

Operating Procedures for Residential Pesticide Exposure Assessment, HED analyzed a 

number of DFR studies and selected a new default value for the fraction of the 

application rate available to be dislodged after a foliar application (FAR). This default 

value is 25% and is based on an analysis of 19 DFR studies where the FAR value ranged 

from 2% to 47%. This value is recommended for use in both residential and occupational 

post-application assessments. Of the analyzed DFR studies, the maximum FAR value 

seen was 47% or approximately two times higher than the default residue transfer value. 

Therefore, the HED has decided that a calculated margin of exposure (MOE) of 

approximately two times higher than the LOC (e.g., an MOE ≥ 200 if the LOC = 100) 

using the default dislodged residue values would provide an adequate margin of safety 

for any potentially higher residues seen in a chemical-specific DFR study. A DFR study 

is required for chlorfenapyr at this time since the dermal MOEs are less than two

times the LOC (i.e., < 200) based on default values for the fraction of application 

rate available for transfer after a foliar application.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Plant Commodities: The enforcement method is designated as M 2427, a gas 

chromatography/electron capture detection (GC/ECD) method with a limit of quantitation (LOQ) 

of 0.05 ppm. Method M 2427 has been subjected to a successful independent laboratory 

validation (ILV) as well as an acceptable radiovalidation using samples obtained from lettuce 

and tomato metabolism studies. HED’s review of PP#6F4716 (Memo, 11/20/96, R. Cook, 

D226458) concluded that method M 2427 is adequate for data collection and tolerance 

enforcement purposes. 

Livestock Commodities: Three different analytical methods for chlorfenapyr residues in milk, 

muscle/fat and liver/kidney are available to support the established permanent tolerances (MRID 

43492857). A satisfactory method trial has been conducted by EPA's Analytical Chemistry 
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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Laboratory for the subject livestock commodity chlorfenapyr methods (i.e. M 2405 for cattle 

liver, M 2398 for cattle muscle, and M2395.01 for cow milk).

2.2.2 Tolerance Recommendations

Tolerances have been established in 40 CFR §180.513 for residues of chlorfenapyr in/on the 

vegetables, fruiting, group 8 at 1.0 ppm and in/on all food commodities in food/feed handling 

areas at 0.01 ppm. The tolerance summary for chlorfenapyr is presented in Table 2.2.2.1. The 

existing tolerances for vegetable, fruiting group 8 (1.0 ppm) needs to be revised to vegetable, 

fruiting, group 8-10.

In addition, the tolerance expression for chlorfenapyr should be updated to reflect current 

Agency policy as follows: 

“Tolerances are established for residues of chlorfenapyr, including its metabolites and 

degradates, in or on the commodities in the table below. Compliance with the tolerance 

levels specified below is to be determined by measuring only chlorfenapyr, 4-bromo-2-

(4-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile, in or 

on the commodity.”

Table 2.2.2.1. Tolerance Summary for Chlorfenapyr

Tolerance (ppm)

Commodity Established Recommended Comments

Vegetable, fruiting, group 8 1.0 1.0 Establish as Vegetable, fruiting, group 8-10

Food commodities in 

food/feed handling areas 0.01 0.01 -

2.2.3 International Harmonization

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

The U.S. and Mexican tolerance definitions are harmonized for residues of chlorfenapyr in/on 

commodities in fruiting vegetable crop group 8. There is an MRL of 0.5 ppm for cotton seed in 

Mexico, which has no U.S. equivalent tolerance. Harmonization with Codex and Canada is not 

an issue. 

2.3 Label Recommendations

 For several occupational scenarios, additional PPE is needed on the Phantom® label (EPA 

Reg. No. 241-392) to reach the LOC of 100 (see Section 9.1). 

 For mixers/loaders/applicators of liquids using a mechanically-pressurized handgun for 

greenhouse applications, there are risks of concern (MOEs = 15-26) even with maximum 

PPE (i.e., double layer, gloves and PF10 respirator). 

 Based on the combined residential estimates for indoor perimeter/spot/bed bug and 

mattress applications (MOEs = 62), as well as aggregate risk incorporating these 

estimates (MOEs = 60), there are risks of concern with coarse-stream applications of 
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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Phantom® (EPA Reg. No. 241-392) for children (1 to <2 years old). However, use of 

equipment with a pin-stream nozzle results in MOEs above the LOC for these uses. 

3.0 Introduction

Chlorfenapyr is a member of the pyrroles class of insecticide/miticides. It controls mites, 

caterpillar pests, thrips, and fungus gnats on fruiting vegetables in greenhouses. Additionally, 

chlorfenapyr controls cockroaches and ants in food/feed handling establishments and other 

structures. Chlorfenapyr also controls termites via surface and subterranean applications. The 

compound is a pro-insecticide; i.e., the biological activity depends on its activation to another 

chemical compound. Oxidative removal of the N-ethoxymethyl group of chlorfenapyr by mixed 

function oxidases forms the compound CL 303,268 (4-bromo-2-(p-chlorophenyl)-5-

(trifluoromethyl)-pyrrole-3-carbontrile.). CL 303,268 uncouples oxidative phosphorylation at 

the mitochondria, resulting in disruption of production of ATP, cellular death, and ultimately 

organism mortality.

This PRA provides information to support the Registration Review of chlorfenapyr and 

addresses the exposures and risk estimates associated with all currently registered uses. This 

document incorporates changes made due to submission of new data and updated HED policies

since the most recent risk assessment (G. Kramer, et al., 10-MAR-2003; D275052). All data 

requirements previously addressed during the scoping process have been satisfied (A. Dunbar; 

26-MAY-2010; D373133).

3.1 Chemical Identity

The chemical structure and nomenclature of chlorfenapyr are presented in Table 3.1.1.

Table 3.1.1. Test Compound Nomenclature.

Common name Chlorfenapyr

PC Code 129093

IUPAC Name 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-trifluoromethyl-1H-pyrrole-3-

carbonitrile

CAS name 4-bromo-2-(4-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)-1H-pyrrole-3-

carbonitrile

CAS registry number 122453-73-0

Registration Review Case No. 7419

Chemical Formula C15H11BrClF3N2O

Chemical structure
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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3.2 Physical/Chemical Characteristics

A table of the physicochemical properties of chlorfenapyr can be found in Appendix B. 

3.3 Pesticide Use Pattern

Chlorfenapyr is registered for use on greenhouse food and non-food crops (greenhouse only), 

and as an insecticide/miticide for use on indoor and outdoor residential sites, food/feed handling 

areas, indoor and outdoor commercial sites (including sewers), and indoor medical sites. It is 

also registered for use on bed bugs. It is currently formulated into SC, EC, and pressurized 

release liquid end-use products (e.g., total release foggers and aerosol cans) containing between

0.05% to 21.45% ai. A summary of application scenarios is presented in Table 3.3.1. The preharvest interval (PHI) and maximum seasonal application rates are not specified on most of the 

labels. Appendix D includes a summary of the end-use products.
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Table 3.3.1. Existing Use Patterns/ Exposure Scenarios for Chlorfenapyr.

Registration Number and 

Product Name Formulationa Application Equipment

Maximum Application 

Rates

Max. No. 

Applications Per 

Season

Use Directions and Limitations REI

Greenhouse ornamentals including Bedding Plants, Cut Flowers, Evergreens, Flowering plants, Foliage Plants, Fruiting Vegetables, Containerized Plants, Ground Covers, Non-Bearing Nut 

Trees, Non-Bearing Vines, Ornamental Trees and Shrubs

499-544

TC-307 Pylon® TR (Total 

Release miticide/

insecticide)b

PRL Total release 

fogger

0.011 lb ai/3000 ft2

(0.163 lb ai/A)

3

Do not make more than 2 consecutive applications. 

Not for indoor, residential use (e.g., homes, 

apartments, mobile homes).

Re-treatment for fruiting vegetables is 5-7 days.

12 hours

Greenhouse (roses, cut flowers, container stock)

241-374

Pylon® SCb

Backpack

Manuallypressurized 

handwand

Mechanicallypressurized 

handgun

0.0016 lb ai/gal 3

Wait at least 5 to 7 days between each application.

Do not apply this product through any type of 

irrigation system.

12 hours

Greenhouse (vegetable, fruiting, group 8-10d)

241-374

Pylon® SCb

Backpack

Manuallypressurized 

handwand

Mechanicallypressurized

handgun

0.20 lb ai/A

0.04 lb ai/gal

3

This product can be applied up to and including the 

day of harvest.

Wait at least 5 to 7 days between each application.

Do not apply this product through any type of 

irrigation system.

Do not apply this product as an ultra-low volume 

spray.

Do not use on tomato varieties with a diameter of less 

than one inch when mature.

12 hours
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Table 3.3.1. Existing Use Patterns/ Exposure Scenarios for Chlorfenapyr.

Registration Number and 

Product Name Formulationa Application Equipment

Maximum Application 

Rates

Max. No. 

Applications Per 

Season

Use Directions and Limitations REI

Residential and Nonagricultural Uses

Commercial and Food Use Site c and Household/domestic dwellings (indoor and outdoor)

7969-285

Prescription Treatment® brand 

Phantom®

(General Pest-Control 

including bed bugs)

PRL 17.5 oz Aerosol 

can

0.5% ai = 

0.005 lb ai/can Not specified

Spot and/or crack and crevice applications.

For sale to, use and storage only by individuals/firms 

licensed or registered by the state to apply termiticide 

and/or general pest-control products.

Do not use in schools when occupied.

Do not apply directly to food, food packaging, or 

food contact surfaces.

Do not make surface applications to mattresses or 

bedding. Mattress treatments must be confined to the 

seams, folds, and edges only.

Do not use to use to treat soil directly.

Do not reapply to treated area more than every four 

weeks.

Not 

applicable

499-548

TC-314 (Phantom®

Pressurized Insecticide 

Formula 2)

(General Pest-Control, 

including bed bugs, and 

Subterranean Termite Control)

499-556

TC-326 (Phantom®

Pressurized Insecticide with 

IGR)

(General Pest-Control, 

including bed bugs, and

Subterranean Termite Control)

241-392

Phantom®

(General Pest-Control 

including bed bugs)

EC

2 lb ai/gal

Manual- or 

Mechanicallypressurized 

handwand/gun

0.5% dilution = 0.05 lb 

ai/gal

Limited exterior 

applications to doors, 

windows, eaves, attic 

vents: 0.00023 lb ai/ft2

Not specified

For sale to, use and storage only by individuals/firms 

licensed or registered by the state to apply termiticide 

and/or general pest-control products.

Do not reapply more often than every four weeks.

Do not make surface applications to mattresses. 

Mattress treatment must be confined to the seams 

folds and edges only.

Not 

applicable
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Table 3.3.1. Existing Use Patterns/ Exposure Scenarios for Chlorfenapyr.

Registration Number and 

Product Name Formulationa Application Equipment

Maximum Application 

Rates

Max. No. 

Applications Per 

Season

Use Directions and Limitations REI

Nonagricultural outdoor buildings/structures

241-392

Phantom®

(Pre-construction and Postconstruction Termiticide Soil 

Treatments)

EC

2 lb ai/gal

Manual- or 

mechnicallypressurized 

handwand/gun

Inline injection 

with lateral 

dispersal nozzle

Trenching and 

rodding

0.25% dilution = 0.0234 lb 

ai/gal

0.0936 lb ai/ft2

Not Specified

For sale to, use and storage only by individuals/firms 

licensed or registered by the state to apply termiticide 

and/or general pest-control products.

Do not reapply more often than every four weeks.

Liquid and foam applications can be made. If foam 

applications are made, 75% of total application must 

be liquid and 25% can be foam.

All applications are to soil. Drilled holes must be 

plugged following application.

Not 

applicable

a. PRL = pressurized release liquid; SC= soluble-concentrate; EC = emulsifiable-concentrate.

b. HED assumes the product Chlorfenapyr SC (assessed in D288704) to be similar in formulation and application to Pylon, the product listed for use on these sites in the Biological 

and Economics Analysis Division’s (BEAD’s) Label Data Report. 

c. This includes commercial storages/warehouse premises, apartments, food storage areas, homes, hospitals, hotels, meat packing and food processing plants, motels, nursing 

homes, restaurants, and other food handling establishments, schools, hospitals/medical institutions, supermarkets, warehouses and other commercial and industrial buildings, 

sewage systems, and zoos. Food handling establishments include dairies/cheese processing plant equipment (food contact), eating establishments, egg packing plants 

(commercial), feed mills/ feed processing plants, and food/grocery/marketing/storage/distribution facility premise.

d See 40 CFR §180.513.
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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3.4 Anticipated Exposure Pathways

The PRD has requested an assessment of human health risk to support Registration Review of all 

existing registered uses of chlorfenapyr. Humans may be exposed to chlorfenapyr via dietary 

exposure from applications to greenhouse fruiting vegetable crops. There are no residential 

handler uses of chlorfenapyr, but there is potential for post-application exposure in residential 

and non-occupational settings. In an occupational setting, applicators may be exposed while 

handling the pesticide prior to application, as well as during application. There is also potential 

for post-application exposure for workers re-entering treated sites. This risk assessment 

considers all of the aforementioned exposure pathways based on the existing uses of 

chlorfenapyr.

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://epa.gov/compliance/ej/resources/policy/exec_order_12898.pdf). As a part of every 

pesticide risk assessment, the Office of Pesticide Programs (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’s National Health and Nutrition Examination Survey, 

What We Eat in America, (NHANES/WWEIA) and are used in pesticide risk assessments for all 

registered food uses of a pesticide. These data are analyzed and categorized by subgroups based 

on age and ethnic group. Additionally, OPP is able to assess dietary exposure to smaller, 

specialized subgroups and exposure assessments are performed when conditions or 

circumstances warrant. Whenever appropriate, non-dietary exposures based on home use of 

pesticide products and associated risks for adult applicators and for toddlers, youths, and adults 

entering or playing on treated areas post-application are evaluated. Further considerations are 

currently in development as OPP has committed resources and expertise to the development of 

specialized software and models that consider lifestyle and traditional dietary patterns among 

specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

Chlorfenapyr is an insecticide/miticide and a member of the class of chemicals known as 

pyrroles. It is a pro-insecticide that is converted to an active form in target organisms. The 

pesticidal mode of action of the active form functions by uncoupling oxidative phosphorylation 

in mitochondria, which disrupts ATP production leading to cell dysfunction and subsequent 

death of the organism. 

4.1 Toxicology Studies Available for Analysis

The toxicological database for chlorfenapyr is complete and adequate for hazard 

characterization, toxicity endpoint selection, and FQPA SF evaluation. Since the scoping 
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document for Registration Review, data evaluation records (DERs) have been updated for 

several guideline studies to reflect current HED policy. Additionally, 28-day dermal, 90-day 

inhalation, dermal penetration, and DNT studies have been submitted and reviewed. A 

subchronic neurotoxicity study was previously requested, but is no longer required because a 

chronic neurotoxicity study was performed. As part of the revised 40 CFR Part 158 Toxicology 

Data Requirements, an immunotoxicity study is necessary for the currently registered uses; 

however the HED Hazard and Science Policy Council (HASPOC) concluded using a weight-ofevidence approach that this study is not required at this time (U. Habiba, 07-JUN-2013, TXR# 

0056692). 

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

In a rat metabolism study, fecal excretion was the major route of elimination (80% of recovered 

radioactivity) with low recoveries of the radioactive chlorfenapyr in urine and tissues. Most of 

the radioactivity was eliminated within 48 hours of dosing. Female rats had greater recovery of 

radioactivity (about 2X at the low dose) in the fat, carcass, and blood at all doses than did males. 

The highest recovery of radioactivity from a single organ was from the liver (0.15-0.48% of the 

administered dose). Parent compound was the major radioactive component found in excreta, 

accounting for approximately 40-70% of the administered doses. Minor amounts of eight 

primary and conjugated metabolites and four unidentified isolated components were detected, 

each at less than 10% of the dosed radioactivity. Liver and kidney contained several primary and 

conjugated metabolites and only minor levels of the parent compound (8.3% of the 

radioactivity in the sample). Identified metabolites were minimally accumulated in tissues and 

primarily excreted in the urine.

4.2.1 Dermal Absorption

A dermal penetration study (MRID 49315901) has been submitted since the most recent risk 

assessment. The dermal absorption was found to be 13% after 8 hours (based on excreta, cage 

wash, blood, plasma, carcass, application site, and the surrounding skin) and should be applied 

for converting oral doses to dermal equivalent doses to assess the potential risk associated with 

dermal exposures of chlorfenapyr. The application site and surrounding skin were included since 

there is ongoing depletion of the dose from the application site following washing and a 

corresponding increase in excreta over time, which suggests the chemical at the application site 

is bioavailable for further skin absorption. The bioavailable amount may be overestimated as

tape stripping was not performed in the study and, as a result, all of the chemical present at the 

application site was included in the dermal absorption calculation.

4.3 Summary of Toxicological Effects

The CNS is the primary target of chlorfenapyr inducing neurohistological changes in the CNS 

from subchronic and chronic dietary administration in mice and rats. Mice exhibited spongiform 

encephalopathy in the brain and myelin of the spinal cord from subchronic exposure and 

vacuolization of the brain, spinal cord, and optic nerve from chronic exposure. Similar findings 

were noted in male rats after subchronic and chronic exposure. Though the observations in the 

subchronic rat study did not show a clear-dose response, they were considered treatment-related 
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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since they are consistent with effects seen in the other subchronic and chronic studies. In 

addition to neuropathology, rats also exhibited neurobehavioral changes on the day of dosing in 

the acute neurotoxicity study. These findings included changes in gait, locomotion, arousal, and 

lethargy. Decreased motor activity was observed in the acute neurotoxicity study as well as in 

offspring in the DNT study. 

Several rat studies noted effects in the liver at doses similar to or above those where CNS effects 

were seen. The liver was identified in metabolism studies as the single organ to have the highest 

recovery of administered dose. Liver weights were increased in the subchronic oral toxicity and 

28-day dermal toxicity studies at 48 mg/kg/day and 835 mg/kg/day, respectively. Liver tumors 

(adenomas and combined adenomas/carcinomas) were also seen in the combined chronic 

toxicity/carcinogenicity study at approximately 30 mg/kg/day. 

There was evidence of increased quantitative susceptibility to offspring in the database as a result 

of chlorfenapyr exposure. In the two-generation reproduction study, decreased pup weights were 

seen at the mid-dose (22.2 and 24.5 mg/kg/day in males and females, respectively) with early 

pup deaths considered adverse at the HDT (44.0 and 48.3 mg/kg/day in males and females, 

respectively). Parental toxicity (decreased body-weight) was only seen at the HDT. It should be 

noted that postmortem examinations for parental animals in this study did not include the CNS. 

In the DNT study, offspring toxicity (decreased motor activity and increased pup deaths on 

postnatal days 1-4) was seen at 10 mg/kg/day in the absence of maternal toxicity. Additional 

effects on the CNS (vacuolation of white matter in the brain and decreased hippocampus size) 

were also observed in offspring at the HDT in this study (15 mg/kg/day). There was no evidence 

of increased susceptibility to offspring in other developmental studies. In both the rat and rabbit 

developmental toxicity studies, although no maternal or developmental effects were noted up to 

the HDTs (30 mg/kg/day and 225 mg/kg/day in the rabbit and rat, respectively), maternal 

observations are limited in these developmental studies. Consequently, the data from the DNT 

are considered more robust for assessing the effects of chlorfenapyr on the nervous system. 

Given the lack of toxicity in the rat and rabbit developmental studies, the early pup deaths in the 

reproduction toxicity and DNT studies are suspected to be the result of postnatal exposure 

through lactation. Chlorfenapyr has a relatively high octanol-water partition coefficient (logKOW

= 4.83) and has been shown to accumulate in milk due to its lipophilic nature in a dietary cow 

study (G. Kramer, 06-AUG-1996, D222004). Additionally, in the rat metabolism study, 

chlorfenapyr was found to accumulate in the fat (0.03-0.35% of the administered dose), such that 

females exhibited greater accumulation than males. This observation suggests chlorfenapyr is 

capable of accumulating in breast milk and likely causing the early pup deaths seen in the 

reproduction toxicity and DNT studies through lactation.

Chlorfenapyr is classified as having moderate acute toxicity via the oral route (Toxicity Category 

II) and low acute toxicity via the dermal and inhalation routes of exposure (Toxicity Category 

III). It is a mild eye irritant, but it is not a dermal irritant or sensitizer. 

Chlorfenapyr did not show any evidence of mutagenicity in in vitro or in vivo studies. The 2003 

Hazard Identification Assessment Review Committee (HIARC) clarified, but did not change the 

1996 cancer classification of “cannot be determined, suggestive” evidence of carcinogenicity for 
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chlorfenapyr. The HIARC indicated that, according to EPA’s July 1999 Draft Guidelines for 

Carcinogen Risk Assessment, the current classification category of “suggestive evidence of 

carcinogenicity, but not sufficient to assess human carcinogenic potential” was a better 

description of the intent of the 1996 Cancer Peer Review Committee.

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

The RAB1 risk assessment team for chlorfenapyr determined that the FQPA SF should be 

reduced to 1X for all exposure scenarios. An acceptable DNT study has been submitted and now 

satisfies the previous data requirement. Although there is evidence of neurotoxicity and 

susceptibility/sensitivity to offspring in the database, the effects are well-characterized with 

clearly established NOAEL/LOAEL values and selected endpoints are protective for the 

observed effects.

4.4.1 Completeness of the Toxicology Database

The existing toxicological database is complete and adequate for characterizing chlorfenapyr

toxicity and quantifying hazard for dietary and occupational exposures. The developmental 

toxicity studies in rats and rabbits, two-generation reproduction toxicity study in rats, and 

neurotoxicity studies in rats (acute, chronic, and DNT) are available to assess potential 

fetal/offspring sensitivity.

4.4.2 Evidence of Neurotoxicity

Although the CNS is the primary target for chlorfenapyr and neurotoxic effects were observed 

across studies (see section 4.3), concern is low since the selected PODs are protective of 

observed neurotoxic effects.

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

Although there is evidence of increased quantitative susceptibility (see section 4.3), concern is 

low since the offspring effects are well-characterized with clearly established NOAEL/LOAEL 

values and the endpoints selected for risk assessment are protective of observed offspring effects.

4.4.4 Residual Uncertainty in the Exposure Database

The exposure databases are sufficient to determine the nature/magnitude of the residue in food. 

Residues in drinking water are not expected from the currently registered uses. The dietary 

exposure analyses are unlikely to underestimate exposure as they incorporated tolerance-level 

residues and 100% CT. The residential post-application exposure assessments are based upon 

the residential Standard Operating Procedures (SOPs). These assessments of exposure are not 

likely to underestimate the resulting estimates of risk from exposure to chlorfenapyr.

4.5 Toxicity Endpoint and Point of Departure Selections

Acute Dietary Endpoint (all populations): The acute reference dose (aRfD) for all populations 
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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was established using the NOAEL of 5 mg/kg/day from the DNT study. The LOAEL of 10 

mg/kg/day is based on increased pup deaths (post-natal days 1-4) and decreased motor activity. 

Exposure through lactation appears to be causing the early pup deaths given no effects were seen 

in the rat and rabbit developmental studies and chlorfenapyr accumulates in milk and fat. As a 

result, the early pup deaths are considered an acute effect. The acute neurotoxicity study is 

supportive of this endpoint (LOAEL = 45 mg/kg/day, NOAEL not established), which yields a 

similar aRfD. Consequently, this endpoint is protective of the general population as well as 

pregnant and nursing females. The aPAD of 0.05 mg/kg/day is derived from the NOAEL of 5 

mg/kg/day and a 100-fold uncertainty factor (UF) (10X for interspecies extrapolation, 10X for 

intraspecies variation, and 1X for FQPA SF).

Chronic Dietary Endpoint (all populations): The DNT and chronic neurotoxicity studies were 

considered co-critical for chronic dietary exposures. These studies are protective of all durations 

of exposure since there is no progression of toxicity with time. The chronic reference dose 

(cRfD) was established using the NOAEL from the DNT study (5 mg/kg/day). The LOAEL for 

the DNT is based on increased pup deaths (post-natal days 1-4) and decreased motor activity. 

The chronic neurotoxicity study LOAEL of 13.6 mg/kg/day (NOAEL = 2.6 mg/kg/day) is based 

on alterations in the myelin of the CNS, which is the target organ of chlorfenapyr, as well as 

body-weight decrements. Lesions of the CNS and skin observed in the mouse carcinogenicity 

study are also supportive of these studies (NOAEL = 2.8 mg/kg/day). The endpoint is 

appropriate for the route and duration of exposure. The cPAD of 0.05 is based on the NOAEL of 

5 mg/kg/day from the DNT study and a 100-fold UF (10X for interspecies extrapolation, 10X for 

intraspecies variation, and 1X for FQPA SF). 

Short- and Intermediate-Term Incidental Oral Endpoint: The DNT study was selected to 

evaluate incidental oral exposures (NOAEL = 5 mg/kg/day). The LOAEL of 10 mg/kg/day is 

based on increased pup deaths (post-natal days 1-4) and decreased motor activity. The 

reproduction toxicity study is supportive of this endpoint with a similar NOAEL of 

approximately 5 mg/kg/day. This study was chosen because it is appropriate for the route of 

exposure, duration, and population of concern. Exposure through lactation appears to be causing 

the early pup deaths given no effects were seen in the rat and rabbit developmental studies and 

chlorfenapyr accumulates in milk and fat. The LOC for incidental oral exposure scenarios is 100 

(10X for interspecies extrapolation, 10X for intraspecies variation, and 1X for FQPA SF). No 

long-term exposure is expected.

Short- and Intermediate-Term Dermal Endpoint: The DNT study was selected to evaluate 

dermal exposures (NOAEL = 5 mg/kg/day). The LOAEL of 10 mg/kg/day is based on increased 

pup deaths (post-natal days 1-4) and decreased motor activity. The reproduction toxicity study is 

supportive of this endpoint with a similar NOAEL of approximately 5 mg/kg/day. This study is 

protective of pregnant and nursing females and appropriate for the duration of concern. 

Exposure through lactation appears to be causing the early pup deaths given no effects were seen 

in the rat and rabbit developmental studies and chlorfenapyr accumulates in milk and fat. The 

route-specific dermal study was not chosen since the DNT provided a lower POD and there was 

increased susceptibility to offspring observed in the DNT and reproduction toxicity studies. The 

LOC for short- and intermediate-term dermal exposure scenarios is 100 (10X for interspecies 

extrapolation, 10X for intraspecies variation, and 1X for FQPA SF when applicable). No long-
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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term exposures are expected based on the use pattern of chlorfenapyr. Since an oral study was 

selected, a dermal absorption factor of 13% should be applied for all dermal exposure scenarios.

Short- and Intermediate-Term Inhalation Endpoint: The DNT study was selected to evaluate 

inhalation exposures (NOAEL = 5 mg/kg/day). The LOAEL of 10 mg/kg/day is based on 

increased pup deaths (post-natal days 1-4) and decreased motor activity. The reproduction 

toxicity study is supportive of this endpoint with a similar NOAEL of approximately 5 

mg/kg/day. This study is protective of pregnant and nursing females and appropriate for the 

duration of concern. Exposure through lactation appears to be causing the early pup deaths given 

no effects were seen in the rat and rabbit developmental studies and chlorfenapyr accumulates in 

milk and fat. The DNT study provides a lower POD than the route-specific inhalation study. 

Additionally, the inhalation study was not chosen since only adults were evaluated and there was 

increased susceptibility to offspring observed in the DNT and reproduction toxicity studies. The 

LOC for short- and intermediate-term inhalation exposure scenarios is 100 (10X for interspecies 

extrapolation, 10X for intraspecies variation, and 1X for FQPA SF when applicable). No longterm exposures are expected based on the use pattern of chlorfenapyr. Inhalation exposure is 

assumed to be equivalent to oral exposure.

4.5.1 Recommendation for Combining Routes of Exposures for Risk Assessment

Based upon common effects and the use of a DNT study for oral, dermal, and inhalation routes, 

these exposures can be combined for all residential (dermal, incidental oral, and inhalation) and 

occupational (dermal and inhalation) scenarios for all durations. 

4.5.2 Cancer Classification and Risk Assessment Recommendation

Chlorfenapyr is classified as “suggestive evidence of carcinogenicity, but not sufficient to assess 

human carcinogenic potential.” A quantitative cancer risk assessment is not required.

4.5.3 Summary of Points of Departure and Toxicity Endpoints Used in Human Health 

Risk Assessment

Table 4.5.3.1. Summary of Toxicological Doses and Endpoints for Chlorfenapyr for Use in Dietary and NonOccupational Human-Health Risk Assessments.

Exposure/ 

Scenario POD Uncertainty/FQPA SF

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary 

(All 

populations)

NOAEL = 

5 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Acute Rfd =

0.05 mg/kg/day

aPAD = 

0.05 mg/kg/day

Developmental Neurotoxicity 

Study (Rat)

LOAEL = 10 mg/kg/day based on 

increased pup deaths (post-natal days 

1-4) and decreased motor activity.
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Table 4.5.3.1. Summary of Toxicological Doses and Endpoints for Chlorfenapyr for Use in Dietary and NonOccupational Human-Health Risk Assessments.

Exposure/ 

Scenario POD Uncertainty/FQPA SF

RfD, PAD, LOC 

for Risk 

Assessment

Study and Toxicological Effects

Chronic 

Dietary (All 

Populations)

NOAEL = 

5 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Chronic Rfd =

0.05 mg/kg/day

cPAD = 

0.05 mg/kg/day

Developmental Neurotoxicity 

Study (Rat)

LOAEL = 10 mg/kg/day based on 

increased pup deaths (post-natal days 

1-4) and decreased motor activity.

Chronic Neurotoxicity Study (Rat)

NOAEL = 2.6 mg/kg/day.

LOAEL = 13.6 mg/kg/day based on 

alterations of the myelin of the CNS 

and decreased water consumption in 

male rats, decreased food 

consumption in females, and 

decreased body-weight in both sexes.

Incidental Oral 

Short-Term 

(1-30 days) and 

IntermediateTerm 

(1-6 months)

NOAEL = 

5 mg/kg/day

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential LOC 

for MOE = 100

Developmental Neurotoxicity 

Study (Rat)

LOAEL = 10 mg/kg/day based on 

increased pup deaths (post-natal days 

1-4) and decreased motor activity.

Dermal ShortTerm 

(1-30 days) and 

IntermediateTerm 

(1-6 months)

NOAEL = 

5 mg/kg/day

Dermal absorption 

factor = 13%

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential LOC 

for MOE = 100

Developmental Neurotoxicity 

Study (Rat)

LOAEL = 10 mg/kg/day based on 

increased pup deaths (post-natal days 

1-4) and decreased motor activity.

Inhalation 

Short-Term 

(1-30 days) and 

Intermediateterm 

(1-6 months)

NOAEL = 

5 mg/kg/day

Inhalation assumed 

equivalent to oral 

UFA = 10X

UFH = 10X

FQPA SF = 1X

Residential LOC 

for MOE = 100

Developmental Neurotoxicity 

Study (Rat)

LOAEL = 10 mg/kg/day based on 

increased pup deaths (post-natal days 

1-4) and decreased motor activity.

Cancer (oral, 

dermal, 

inhalation)

Classified as “suggestive evidence of carcinogenicity, but not sufficient to assess human 

carcinogenic potential.” A cancer risk assessment is not required.

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. 
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Table 4.5.3.2. Summary of Toxicological Doses and Endpoints for Chlorfenapyr for Use in Occupational 

Human-Health Risk Assessments.

Exposure/ 

Scenario POD UFs LOC for Risk Assessment Study and Toxicological Effects

Dermal

Short-Term 

(1-30 days) 

and 

IntermediateTerm 

(1-6 months)

NOAEL = 

5 mg/kg/day

Dermal absorption 

factor = 13%

UFA = 10X

UFH = 10X

Occupational LOC 

for MOE = 100

Developmental Neurotoxicity 

Study (Rat)

LOAEL = 10 mg/kg/day based on 

increased pup deaths (post-natal 

days 1-4) and decreased motor 

activity.

Inhalation 

Short-Term 

(1-30 days) 

and 

Intermediateterm 

(1-6 months)

NOAEL = 

5 mg/kg/day

Inhalation assumed 

equivalent to oral

UFA = 10X

UFH = 10X

Occupational LOC 

for MOE = 100

Developmental Neurotoxicity 

Study (Rat)

LOAEL = 10 mg/kg/day based on 

increased pup deaths (post-natal 

days 1-4) and decreased motor 

activity.

Cancer (oral, 

dermal, 

inhalation)

Classified as “suggestive evidence of carcinogenicity, but not sufficient to assess human 

carcinogenic potential.” A cancer risk assessment is not required.

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

the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = 

no-observed adverse-effect level. LOAEL = lowest-observed adverse-effect level. UF = uncertainty factor. UFA = extrapolation 

from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population 

(intraspecies). MOE = margin of exposure. LOC = level of concern. 

4.6 Endocrine Disruptor Screening Program

As required by Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and Federal Food, 

Drug, and Cosmetic Act (FFDCA), EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic, and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its reregistration decision for chlorfenapyr, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p), chlorfenapyr is 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 
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will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list 

of chemicals identified for EDSP screening was published on June 14, 20131and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.2

5.0 Dietary Exposure and Risk Assessment 

For this risk assessment, a new dietary exposure/risk assessment was conducted to incorporate 

updates according to current HED policy.

The nature of the residue in plants and livestock is adequately understood based on acceptable 

metabolism studies conducted on cotton, citrus, lettuce, potato, tomato, ruminants, and poultry. 

Metabolism of chlorfenapyr in plants proceeds via: 1) N-dealkylation of the parent compound; 

and 2) oxidation of the dealkylated metabolite. 

5.1 Residues of Concern Summary and Rationale

The permanent tolerance expression for all commodities is in terms of parent only; however, 

chlorfenapyr dietary risk assessments should include, in addition to the parent, two chlorfenapyr 

metabolites (CL 303,268 and 325,195) for ruminant meat byproducts and four chlorfenapyr 

metabolites (CL 303,268; 325,195; 152,835; and 325,157) for poultry meat byproducts (see 

Table 5.1.1) (G. Otakie; 10-JUL-1996; D227383). Residues in drinking water are not of concern 

for chlorfenapyr, as contamination of drinking water sources is not expected to occur based on 

current use patterns.

The tolerance expression for chlorfenapyr needs to be updated to reflect current Agency policy

as follows: 

“Tolerances are established for residues of chlorfenapyr, including its metabolites and 

degradates, in or on the commodities in the table below. Compliance with the tolerance 

levels specified below is to be determined by measuring only chlorfenapyr, 4-bromo-2-

(4-chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile, in or 

on the commodity.”

 

1

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

2 See http://www.epa.gov/endo/.
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Table 5.1.1. Summary of Metabolites and Degradates to be included in Risk Assessment and Tolerance 

Expression.

Matrix Residues Included in Tolerance Expression 

for Compliance Monitoring Residues Included in Risk Assessment1

Plants

Primary

Crop Chlorfenapyr Chlorfenapyr

Rotational 

Crop Not Applicable Not Applicable

Livestock (Ruminant) Chlorfenapyr

Chlorfenapyr for ruminant except byproducts. 

Parent, two chlorfenapyr metabolites (CL 303,268 

and 325,195) for ruminant meat byproducts only.

Livestock (Poultry) Chlorfenapyr

Chlorfenapyr for poultry except byproducts. 

Parent, and four metabolites CL 303,268, 325,195, 

152,835 and 325,157 for poultry meat byproducts 

only.

Drinking Water Not Applicable Not Applicable

1 Metabolite nomenclature:

CL 303,268 is 4-bromo-2-(p-chlorophenyl)-5-(trifluoromethyl)-pyrrole-3-carbontrile.

CL 325,195 is 2-(p-chlorophenyl)-5-hydroxy-4-oxo-5-(trifluoromethyl)-2-pyrrolidine-3-carbonitrile.

CL 152,835 is {[2-(p-chlorophenyl)-3-cyano-5-(trifluoromethyl)pyrrol-1-yl]methoxy}-acetic acid.

CL 325,157 is {[3-bromo-5-(p-chlorophenyl)-4-cyano-2-(trifluoromethyl)pyrrol-1-yl]methoxy}-acetic acid.

5.2 Food Residue Profile

Fruiting Vegetables: Greenhouse trials were conducted on tomatoes, bell peppers, and jalapeño

peppers. The 2 lb/gal SC formulation of chlorfenapyr was foliarly applied five times to these 

crops, with a 5-day retreatment interval, at 0.18-0.21 lb ai/A per application for a total rate of 

~1.0 lb ai/A (~1.7X the maximum proposed seasonal rate of 0.6 lb ai/A for greenhouse-grown 

fruiting vegetables). At the proposed 0-day PHI, residues of chlorfenapyr were 0.23-0.34 ppm 

in/on treated tomatoes, 0.31-0.39 ppm in/on treated bell peppers, and 0.60-0.65 ppm in/on treated 

jalapeño peppers. Supporting data showed that residues generally declined with corresponding 

increases in the PHI. 

Food Handling Establishments: BASF submitted data depicting the magnitude of chlorfenapyr 

residues resulting from application in a food-handling establishment to support a revised 

application request for nonfood indoor use of chlorfenapyr. Residues were less than the LOQ 

(<0.01 ppm) in/on two samples each of covered and uncovered composited meal samples 

collected 1, 4, 8, and 12 hours after one or two applications of chlorfenapyr at 0.5% ai in 1 gallon 

of spray suspension/1000 square feet. Residues of chlorfenapyr were less than the LOQ (<0.01 

ppm) in/on four samples each of covered and uncovered untreated composited meals (residue 

values of <1.44 to <1.65 ppb were reported). 

5.3 Water Residue Profile

There are no existing or proposed uses of chlorfenapyr expected to result in contamination of 

drinking water.
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5.4 Dietary Risk Assessment

5.4.1 Description of Residue Data Used in Dietary Assessment

An acute and chronic dietary (food only) risk assessment was conducted using the Dietary 

Exposure Evaluation Model - Food Consumption Intake Database (DEEM-FCID), Version 3.16, 

which uses 2003-2008 food consumption data from the U.S. Department of Agriculture’s 

NHANES/WWEIA. The analyses were conducted in support of registration review.

The acute dietary exposure analysis (food only) for all population subgroups, including infants 

and children, was unrefined and used tolerance-level residues and 100% CT. As per HED 

policy, tolerances for food/feed handling establishments are not included in the acute dietary 

assessment unless the food/feed handling establishment is the only use. This is not the case for 

chlorfenapyr. DEEM (ver. 7.81) processing factors were set to 1 for all commodities except 

tomato. Registered uses of chlorfenapyr on fruiting vegetables are for applications to greenhouse 

grown commodities. Greenhouse grown tomatoes are not typically considered to be processed; 

however, there is potential for imported tomatoes that have been treated with chlorfenapyr to be 

processed. As a result, default processing factors for tomato juice (1.5X), paste (5.4X), puree 

(3.3X), and dried (14.3X) were used in dietary analyses to account for imported tomato 

commodities. 

The chronic dietary exposure analysis (food only) for the all population subgroups was unrefined 

and used tolerance-level residues and 100% CT. As most tolerances for chlorfenapyr are for 

food or feed handling establishment uses and residues are expected to be incurred after 

processing, DEEM (ver. 7.81) processing factors were set to 1 for all commodities except 

tomato. Registered uses of chlorfenapyr on fruiting vegetables are for applications to greenhouse 

grown commodities. Greenhouse grown tomatoes are not typically considered to be processed; 

however, there is potential for imported tomatoes that have been treated with chlorfenapyr to be 

processed. As a result, default processing factors for tomato juice (1.5X), paste (5.4X), puree 

(3.3X), and dried (14.3X) were used in dietary analyses to account for imported tomato 

commodities. 

5.4.2 Acute Dietary Risk Assessment

The acute risk estimate utilizes 14% (0.006871 mg/kg/day) of the aPAD for the U.S. population 

at the 95th percentile of exposure. The most highly exposed population subgroup was children 3 

to 5 years old, which utilized 35% (0.017323 mg/kg/day) of the aPAD at the 95th percentile of 

exposure. Thus, acute dietary exposure to chlorfenapyr for all population subgroups is not of 

concern. 

5.4.3 Chronic Dietary Risk Assessment

The chronic risk estimate utilizes 3.8% (0.001900 mg/kg/day) of the cPAD for the U.S. 

population. The most highly exposed population subgroup was children 1 to 2 years old, which 

utilized 9.4% (0.004715 mg/kg/day) of the cPAD. Thus, chronic dietary exposure to 

chlorfenapyr for all population subgroups is not of concern. 
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5.4.4 Cancer Dietary Risk Assessment

Chlorfenapyr is classified as suggestive evidence of carcinogenicity, but not sufficient to assess 

human carcinogenic potential. Therefore, a quantitative cancer dietary exposure assessment is 

not required for chlorfenapyr.

5.4.5 Summary Table

Table 5.4.5.1. Summary of Dietary (Food Only) Exposure Risk for Chlorfenapyra.

Population Subgroup

Acute Dietary (95th Percentile) Chronic Dietary

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure(mg/kg/day) % cPAD

General U.S. Population 0.006817 14 0.001900 3.8

All Infants (<1 year old) 0.007366 15 0.001462 2.9

Children 1-2 years old 0.017222 34 0.004715 9.4

Children 3-5 years old 0.017323 35 0.004633 9.3

Children 6-12 years old 0.010166 20 0.002838 5.7

Youth 13-19 years old 0.006091 12 0.001761 3.5

Adults 20-49 years old 0.005838 12 0.001658 3.3

Adults 50-99 years old 0.005115 10 0.001378 2.8

Females 13-49 years old 0.005574 11 0.01545 3.1

a The values for the highest exposed population for each type of risk assessment are bolded.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

6.1 Residential Handler Exposure

HED uses the term “handlers” to describe those individuals who are involved in the pesticide 

application process. There are four labels [EPA Reg. No. 7969-285 Prescription Treatment®

brand Phantom®, EPA Reg. No. 499-548 TC-314 (Phantom® Pressurized Insecticide Formula 2), 

EPA Reg. No. 499-556 TC-326 (Phantom® Pressurized Insecticide with IGR), and EPA Reg. 

No. 241-392 Phantom®] that have uses in residential settings. These uses are for general pestcontrol (including bed bugs) and allow for spot and crack/crevice applications in residential sites

(for example, surfaces beneath cabinets and sinks, windows, and mattress seams). However, 

there are currently no registered residential uses that permit residential handlers to use the 

products – all labels indicate that products are “for sale to, use and storage only by 

individuals/firms licensed or registered by the state to apply termiticide and/or general pestcontrol products.” Therefore, residential handler assessments were not conducted.

6.2 Post-Application Exposure

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

an environment that has been previously treated with chlorfenapyr. The quantitative 

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

scenarios: 

 Post-application inhalation exposure to adults and children (1 to <2 years old) after 
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indoor perimeter/spot/crack and crevice applications.

 Post-application dermal exposure to adults and children (1 to <2 years old) after indoor 

perimeter/spot/crack and crevice applications.

 Post-application incidental oral exposure to children (1 to <2 years old) after indoor 

perimeter/spot/crack and crevice applications.

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

Appendix in the 2012 Residential SOPs3. While not the only lifestage potentially exposed for 

these post-application scenarios, the lifestage that is included in the quantitative assessment is 

health protective for the exposures and risk estimates for any other potentially exposed lifestage. 

Based on the suggested retreatment interval for the proposed product and the use pattern, it is 

anticipated that exposures will be short-term in duration only. The short-term assessment has 

assumed no dissipation (i.e., day zero residues) for the entire exposure duration (up to 30 days). 

In addition, the short- and intermediate-term PODs are the same; therefore, the short-term 

assessment is expected to be protective of any repeated exposure for longer than 30 days.

6.2.1 Post-application Inhalation Exposure and Risk Estimates

Post-application inhalation exposure occurs while occupying living spaces within a residence 

after a pesticide treatment has occurred. Post-application inhalation exposure to chlorfenapyr 

can result from the registered perimeter/spot/crack and crevice pest-control use (including 

control of bed bugs) from the volatilization of the pesticide after application. 

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

post-application inhalation risk assessment. Each assumption and factor is detailed in the 2012 

Residential SOPs3and summarized in the most recent occupational and residential exposure 

(ORE) memo (L. Venkateshwara; 8-MAY-2014; D417598). The algorithms used to estimate 

residential post-application inhalation exposure and dose can be found in Appendix C and/or the 

2012 Residential SOPs3.

All post-application inhalation scenarios resulted in MOEs greater than the LOC for children and 

adults and, therefore, are not of concern. Table 6.2.1.1 summarizes the post-application 

inhalation exposure and risk from the indoor uses of chlorfenapyr.

Table 6.2.1.1. Post-application Inhalation Exposure and Risk Estimates for Children 

and Adults.

Lifestage MLabel (mg)a

Inhalation Dose 

(mg/kg/day)b,c

Short-term 

Inhalation MOEd

Adult

11,350

0.0001 50,000

Child 1 to < 2

years old 0.00037 13,000

a. Mass of active ingredient applied determined from product label (mg). 

b. Inhalation Dose (mg/kg/day) = Exposure (mg/day) * Inhalation absorption factor (unitless) / Body-Weight (kg).

c. Exposure (mg/day) = IR*MLabel * 1 - [((ACH * e-k*ET) – (K e

-ACHET))]

 ACH * Vroom ACH-k

d. Inhalation MOE = NOAEL (5 mg/kg/day) / Inhalation dose (mg/kg/day). 

 

3 Available: http://www.epa.gov/pesticides/science/residential-exposure-sop.html
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6.2.2 Post-application Dermal Exposure and Risk Estimates

Post-application dermal exposure can result from pesticide residue transfer to the skin of 

individuals who contact previously treated indoor surfaces (e.g., carpets, floors, furniture, and 

other surfaces) during standard activities. For purposes of assessing dermal post-application 

exposure resulting from the use of chlorfenapyr to treat indoor pests (including bed bugs), HED 

has performed an indoor surface (i.e., perimeter/spot/bed bug and crack and crevice) assessment 

in addition to performing an assessment for treated mattresses. For the bed bug use, applications 

are allowed for mattresses (seams, folds, and edges). The label does not allow for surface 

applications to mattresses. The assessment for the mattress application is based on an 

assumption regarding the amount of product applied per area (i.e., a twin-size bed). 

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

post-application dermal risk assessment. Each assumption and factor is detailed in the 2012 

Residential SOPs3and summarized in the most recent ORE memo (L. Venkateshwara; 8-MAY2014; D417598). The algorithms used to estimate residential post-application dermal exposure 

and dose can be found in Appendix C and/or the 2012 Residential SOPs3.

Table 6.2.2.1 summarizes the dermal post-application exposure and risk estimates from the 

perimeter/spot/bed bug use of chlorfenapyr. All post-application dermal scenarios resulted in 

MOEs greater than the LOC for children and adults and, therefore, are not of concern.

Table 6.2.2.2 summarizes the post-application dermal exposure and risk from the bed bug use on 

mattresses. All post-application dermal scenarios for the bed bug use on mattresses resulted in 

MOEs greater than the LOC and are not of concern. 

Table 6.2.2.1. Post-application Dermal Exposure and Risk Estimates for Adults and Children 1 to < 2 

years old for the Use of Chlorfenapyr.

Surface Type Lifestage DepRa (μg/cm2)

Dermal Dose b

(mg/kg/day) Dermal MOEc

Perimeter/Spot/Bed bug (coarse)

Carpet

Adult

4.5

0.028 180

Child 1 to < 2 

years old 0.023 220

Hard Surfaces

Adult 0.0092 540

Child 1 to < 2 

years old 0.015 330

Perimeter/Spot/Bed bug (pin-stream)

Carpet

Adult

1.1

0.0068 740

Child 1 to < 2 

years old 0.0056 890

Hard Surfaces

Adult 0.0023 2,200

Child 1 to < 2 

years old 0.0037 1,300

Crack and Crevice

Carpet

Adult

0.3

0.0018 2,700

Child 1 to < 2 

years old 0.0015 3,300
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Table 6.2.2.1. Post-application Dermal Exposure and Risk Estimates for Adults and Children 1 to < 2 

years old for the Use of Chlorfenapyr.

Surface Type Lifestage DepRa (μg/cm2)

Dermal Dose b

(mg/kg/day) Dermal MOEc

Hard Surfaces

Adult 0.00061 8,100

Child 1 to < 2 

years old 0.0010 4,900

a. DepR = Deposited residue based on default assumptions in HED’s Residential SOPs.

b. Dose (mg/kg/day) = Deposited residue (μg/cm2) * Fraction transferred * Transfer coefficient (cm2/hr) * Exposure time 

(hr/day) * Conversion factor (0.001 mg/μg) * Dermal Absorption Factor (13 %) / Body-Weight (69 kg for adults and 11 kg 

for children 1 to < 2 years old).

c. MOE = POD (mg/kg/day) / Dose (mg/kg/day), where Short-term dermal POD = NOAEL of 5 mg/kg/day and LOC = 100 

for adults and children (1 to < 2 years old).

Table 6.2.2.2. Post-application Dermal Exposure and Risk Estimates for Adults and 

Children 1 to < 2 years old for Bed Bug Mattress Use.

Surface Type Lifestage

Deposited 

Residue 

(μg/cm2)

a

Dermal Dose 

(mg/kg/day)b Dermal MOEc

Mattress

Adult

24.3

0.013 380

Child 1 to <2

years old 0.03 160

a. Residue value determined based on application rate (0.05 lb ai/gal) and assumptions for area treated and amount applied (see 

Appendix and Residential SOPs).

b. Dermal dose (mg/kg/day) = Surface residue (μg/cm2) * Surface area / Body-weight Ratio (cm2/kg) * Fraction of body that contacts 

residue (0.5) * Conversion factor (0.001 mg/μg) * Fraction transferred (0.06) * Protection factor (0.5) * Dermal Absorption Factor (13 

%).

c. MOE = POD (NOAEL = 5 mg/kg/day) / Dose (mg/kg/day), mg/kg/day and LOC = 100 for adults and children 1 to < 2 years old).

6.2.3 Post-application Incidental Oral Exposure and Risk Estimates

Post-application incidental oral exposure resulting from hand-to-mouth and object-to-mouth 

activities can occur as a result of the indoor perimeter/spot/bed bug application and the bed 

bug/mattress use. Only incidental oral exposures resulting from the indoor surface application 

have been assessed here since they are considered to be protective of the mattress application for 

the following reasons: (1) a protection factor of 0.5 is assumed for the mattress exposures due to 

the presence of a bed sheet over the mattress, and (2) the replenishment interval for hand-tomouth activity is assumed to be less while a child is sleeping than while they are awake. 

Table 6.2.3.1 summarizes the MOEs for hand-to-mouth transfer of pesticide residues from the 

indoor perimeter/spot/bed bug use. All hand-to-mouth post-application exposure scenarios 

resulted in MOEs higher than 100 and are therefore not of concern.

Table 6.2.3.2 summarizes the MOEs for object-to-mouth exposure of pesticide residues from the 

indoor perimeter/spot/bed bug use. All object-to-mouth post-application exposure scenarios 

resulted in MOEs higher than 100 and are therefore not of concern.
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Table 6.2.3.1. Post-application Incidental Oral (Hand-to-Mouth) Exposure and Risk 

Estimates for Children for Perimeter/Spot/Bed Bug Use of Chlorfenapyr.

Surface Type

Dermal 

Exposurea

(mg/day)

Faihandsb SAH

c

(cm2)

HRd

(mg/cm2)

Oral Dosee

(mg/kg/day)

Incidental Oral 

MOEf

Perimeter/Spot/Bed bug (coarse)

Carpet

4.5 0.15 150

0.0010 0.026 190

Hard Surfaces 0.0006 0.009 570

Perimeter/Spot/Bed bug (pin-stream)

Carpet

1.1 0.15 150 0.0002

0.0065 770

Hard Surface 0.0021 2,300

Crack and Crevice – Carpets

Carpet

0.3 0.15 150 0.0001

0.0018 2,800

Hard Surface 0.00059 8,500

a. Dermal exposure value from Table 6.2.2.1.

b. Fraction of ai on hands.

c. Surface area of the hand (cm2).

d. Hand residue loading (mg/cm2) = (Faihands * Dermal exposure) / (SAH * 2).

e. Oral Dose (mg/kg/day) = Exposure (mg/day)/ Body-Weight (11 kg); where Exposure (mg/day) = HR * (FM * SAH) * (ET * 

N_Replen) * [1-(1-SE)(Freq_Replen / N_Replen)].

f. MOE = POD (mg/kg/day) / Daily Dose (mg/kg/day); incidental oral POD = NOAEL = 5 mg/kg/day and LOC =100.

Table 6.2.3.2. Post-application Incidental Oral (Object-to-Mouth) Exposure and Risk 

Estimates for Perimeter/Spot/Bed Bug Use of Chlorfenapyr.

Surface Type DepRa

(μg/cm2)

Fo

b ORc Oral Dosed

(mg/kg/day)

Incidental Oral 

MOEe

Perimeter/Spot/Bed bug (coarse)

Carpet

4.5

0.06 0.270 0.004 1,400

Hard Surfaces 0.08 0.360 0.002 2,100

Perimeter/Spot/Bed bug (pin-stream)

Carpet

1.1

0.06 0.066 0.0009 5,800

Hard Surface 0.08 0.088 0.0006 8,700

Crack and Crevice – Carpets

Carpet

0.3

0.06 0.018 0.0002 21,000

Hard Surface 0.08 0.024 0.0002 32,000

a. DepR = Deposited residue 

b. Fraction of residue transferred to an object (unitless).

c. Chemical residue loading on the object (μg/cm2) = Deposited residue (μg/cm2) * Fo.

d. Oral Dose (mg/kg/day) = Exposure (mg/day)/ Body-Weight (11 kg). 

e. MOE = POD (mg/kg/day) / Daily Dose (mg/kg/day); incidental oral POD = NOAEL = 5 mg/kg/day and LOC = 100.
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6.3 Combined Residential Risk Estimates (Multiple Exposure Scenarios)

There is the potential for post-application dermal, oral, and inhalation exposure for children and 

post-application dermal and inhalation exposure for adults resulting from use of chlorfenapyr as 

an indoor perimeter/spot/bed bug and bed bug/mattress use. As indicated previously, the dermal, 

incidental oral, and inhalation endpoints are the same and have the same LOCs; therefore, these 

routes were combined for a total MOE. 

The incidental oral scenarios (i.e., hand-to-mouth and object-to-mouth) should be considered 

inter-related and it is likely that they occur interspersed amongst each other across time. 

Combining these scenarios with the dermal and inhalation exposure scenarios would be overly 

conservative because of the conservative nature of each individual assessment. Therefore, the 

post-application exposure scenarios that were combined for children 1 to < 2 years old are the 

dermal, inhalation and hand-to-mouth scenarios. This combination should be considered a 

protective estimate of children’s exposure to pesticides used indoors.

A summary of the combined MOEs for the bed bug scenario is provided in Table 6.3.1. The 

combined residential estimate for indoor perimeter/spot/bed bug and mattress applications for 

adults is greater than the LOC and is therefore not a concern. For children (1 to <2 years old), 

the combined MOE with coarse-stream applications yields a combined MOE less than the LOC. 

However, use of equipment with a pin-stream nozzle though results in a combined MOE for 

children (1 to <2 years old) that is above the LOC. 

Table 6.3.1. Combined Residential Exposure and Risk Estimates 

Population Post-application Scenarios Daily Dose

(mg/kg/day)a MOEb Combined MOEc

Short-and Intermediate-term

Adult

Dermal – Perimeter/Spot/Bed Bug (coarse) 0.028 180

Inhalation – Perimeter/Spot/Bed Bug 0.0001 50,000 120

Dermal - bed bug/mattress 0.013 380

Adult

Dermal – Perimeter/Spot/Bed Bug (pin-stream) 0.0068 740

Inhalation – Perimeter/Spot/Bed Bug 0.0001 50,000 250

Dermal - bed bug/mattress 0.013 380

Child (1 to <2 

years old)

Dermal - Perimeter/Spot/Bed Bug (coarse) 0.023 220

62

Inhalation – Perimeter/Spot/Bed Bug 0.00037 13,000

Hand-to-Mouth – Perimeter/Spot/Bed Bug (coarse) 0.027 190

Dermal – bed bug/mattress 0.03 160

Child (1 to <2 

years old)

Dermal - Perimeter/Spot/Bed Bug(pin-stream) 0.0056 890

120

Inhalation – Perimeter/Spot/Bed Bug 0.00037 13,000

Hand-to-Mouth – Perimeter/Spot/Bed Bug (pin-stream) 0.0065 770

Dermal – bed bug/mattress 0.03 160

Bolded values are below the LOC of 100.

a. For calculations of Daily Dose, see Tables 6.2.2.1, 6.2.2.2, 6.2.3.1, and 6.2.3.2.

b. MOE = NOAEL (5 mg/kg/day) / Dose (mg/kg/day).

c. Adult Combined MOE = 1/ [(1/MOEDermal – Perimeter/Spot/Bed Bug) + (1/MOEDermal – bed bug mattress) + (1/MOEInhalation)]

Child (1 to <2 years old) Combined MOE = 1/ [(1/MOEDermal – Perimeter/Spot/Bed Bug) + (1/MOEDermal – bed bug mattress) + (1/MOEInhalation) + 

(1/MOEHand-to-Mouth)]
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6.4 Residential Risk Estimates for Use in Aggregate Assessment

Table 6.4.1 reflects the residential risk estimates that are recommended for use in the aggregate 

assessment for chlorfenapyr.

 The recommended residential exposure for use in the adult aggregate assessment reflects 

combined post-application dermal and inhalation exposure from indoor applications 

(surfaces and mattresses) to control bed bugs.

 The recommended residential exposure for use in the children 1 to <2 years old aggregate 

assessment reflects combined post-application dermal, inhalation, and hand-to-mouth 

exposures from indoor applications (surfaces and mattresses) to control bed bugs.

Table 6.4.1. Recommendations for the Residential Exposures for the Chlorfenapyr Aggregate Assessment.

Lifestage Exposure 

Scenario

Dose (mg/kg/day)1 MOE2

Dermal3Inhalation Oral Total Dermal Inhalation Oral Total

Adult 

Male/Female

Postapplication 

exposure 

from indoor 

bed bug 

applications 

(coarse)

0.041 0.0001 N/A 0.041 120 50,000 N/A 120

Postapplication 

exposure 

from indoor 

bed bug 

applications 

(pin-stream)

0.020 0.0001 N/A 0.020 250 50,000 N/A 250

Child

Postapplication 

exposure 

from indoor 

bed bug 

applications 

(coarse)

0.053 0.00037 0.027 0.08 90 13,000 190 62

Postapplication 

exposure 

from indoor 

bed bug 

applications 

(pin-stream)

0.0356 0.00037 0.0065 0.042 140 13,000 770 120

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

applicable).

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

where applicable.

3Dermal values represent the sum of post-application exposure from perimeter/spot/bed bug and bed bug/mattress.

6.5 Spray Drift

A spray drift assessment is not included because chlorfenapyr is not registered on use sites that 

are likely to result in spray drift. As stated above, chlorfenapyr is registered for use only on 

greenhouse food and non-food crops, and as an insecticide/termiticide for use on indoor and 
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outdoor residential sites, food/feed handling areas, indoor and outdoor commercial sites 

(including sewers), and indoor medical sites. 

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and 

risks from three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from relevant sources are added together and compared to quantitative 

estimates of hazard (e.g. a NOAEL or PAD), or the risks themselves can be aggregated. When 

aggregating exposures and risks from various sources, HED considers both the route and 

duration of exposure.

For chlorfenapyr, aggregate exposure and risk assessments were assessed for the following 

scenarios: acute aggregate exposure, short- and intermediate-term aggregate exposure, and 

chronic aggregate exposure. Chlorfenapyr is classified as “suggestive evidence of 

carcinogenicity, but not sufficient to assess human carcinogenic potential”; therefore, a cancer 

aggregate risk assessment was not performed.

7.1 Acute Aggregate Risk

The acute aggregate risk is equivalent to the acute dietary risk estimates. The acute dietary 

exposure estimates are not of concern to HED (<100% aPAD) for the general U.S. population 

and all population subgroups (see Section 5.4.2).

7.2 Short- and Intermediate-Term Aggregate Risk

Short-term (1 to 30 day) and intermediate-term (1 to 6 months) aggregate risk assessments are 

necessary since there is potential for post-application exposure from the uses of chlorfenapyr in 

residential settings. Since the short-term assessment assumed no dissipation (i.e., day-zero 

residues) for the entire exposure duration (up to 30 days), and the short- and intermediate-term 

PODs are the same, the short-term assessment is expected to be protective of intermediate-term 

exposure durations. 

For the short-term aggregate risk assessment, potential residential exposures were combined with 

dietary exposures. Specifically, the short-term aggregate assessment for adults combines dietary 

exposures with potential combined post-application dermal and inhalation exposures from indoor 

applications (surfaces and mattresses) to control bed bugs. For children 1 to <2 years old , the 

short-term aggregate assessment combines dietary exposure with potential combined postapplication dermal, inhalation, and incidental oral exposure from indoor applications (surfaces 

and mattresses) to control bed bugs. See Table 6.4.1 for more information on the residential risk 

estimates that are recommended for use in the aggregate assessment for chlorfenapyr. 

The short-term residential exposure estimates were aggregated with the average dietary exposure

to provide a worst-case estimate of short-term aggregate risk for adults and children (1 to <2 

years old). The short-term aggregate MOEs for adults are greater than the LOC and are therefore 

not of concern. For children (1 to <2 years old), the short-term aggregate exposure with coarse-
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stream applications yields an aggregate MOE less than the LOC. However, use of equipment 

with a pin-stream nozzle though results in an aggregate MOE for children (1 to <2 years old) that 

is above the LOC. Short-term aggregate MOEs are protective of intermediate-term exposure 

durations. 

Table 7.2.1. Short- and Intermediate-Term Aggregate Risk Calculations for Chlorfenapyr.

Population

Subgroups

Short-Term Scenario

NOAEL

(mg/kg/day) LOC1 Max Exposure2(mg/kg/day)

Average Dietary 

Exposure

(mg/kg/day)

Residential 

Exposure3

(mg/kg/day)

Aggregate MOE

(dietary and 

residential)4

Adult (coarse) 5 100 0.05 0.001900 0.041 120

Adult

(pin-stream) 5 100 0.05 0.001900 0.020 228

Children 1 to <2

years old

(coarse)

5 100 0.05 0.004715 0.08 60

Children 1 to <2

years old

(pin-stream)

5 100 0.05 0.004715 0.042 110

The bolded value is below the LOC of 100.

1The LOC (target MOE) includes 10X for interspecies extrapolation and 10X for intraspecies variation.

2 Maximum exposure (mg/kg/day) = NOAEL/LOC.

3 Residential exposure = post-application dermal and inhalation exposure for adults and post-application dermal, inhalation, and

incidental oral exposure for children 1 to <2 years old. 

4 Aggregate MOE = [NOAEL ÷ (Avg. Dietary Exposure + Residential Exposure)]. 

7.3 Chronic Aggregate Risk

There are no chronic residential exposure scenarios; therefore, the chronic aggregate risk is

equivalent to the chronic dietary risk estimate. The chronic dietary exposure estimates are not of 

concern to HED (<100% cPAD) for the general U.S. population and all population subgroups

(see Section 5.4.3).

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

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

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that chlorfenapyr has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s OPP concerning common mechanism determinations and 

procedures for cumulating effects from substances found to have a common mechanism on 

EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

9.1 Short- and Intermediate-Term Handler Risk
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HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

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

that can potentially be used, occupational handler dermal and inhalation exposures are expected 

from the existing uses of chlorfenapyr. The quantitative exposure/risk assessment developed for 

occupational handlers is based on the following scenarios that cover all the registered uses of 

chlorfenapyr: 

 Mixing/loading/applying liquids via injector (termiticide).

 Mixing/loading/applying liquids via mechanically-pressurized handgun.

 Applying pressurized liquids via ready-to-use aerosol cans.

 Mixing/loading/applying liquids via manually-pressurized handwand.

 Mixing/loading/applying liquids via backpack sprayer.

In addition to the above exposure scenarios, there is also a total release fogger product registered 

for use in greenhouses. An assessment of handler exposure from the use of total release foggers 

was not performed because dermal and inhalation exposure is expected to be negligible based on 

the use pattern for this method of application. A total release fogger is an aerosol pesticide 

device designed to automatically release its total content in one operation for the purpose of 

creating a permeating fog within a space to deliver the pesticide throughout the space. 

Therefore, total release aerosols do not need any other application equipment (PR NOTICE 98-6, 

1998). As a common integrated pest management (IPM) and preventive safety practice, if 

multiple foggers are to be activated, the labels typically recommend that the handler “start at the 

far end of the area, opposite from the exit door, activating and placing cans as you move across 

the area until you have reached the exit door.” Once the handler has left the area, the labels also 

direct users to stay out of the treated area for a certain amount of time and to ventilate the area 

before re-entry. Appropriate safety directions and re-entry restrictions should be included on the 

label.

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

handler risk assessments. Each assumption and factor is detailed in the most recent ORE memo 

(L. Venkateshwara; 8-MAY-2014; D417598). The algorithms used to estimate non-cancer 

exposure and dose for occupational handlers can be found in Appendix C.

Most occupational handler inhalation risk estimates resulted in MOEs greater than the LOC at 

baseline or with PPE, and therefore, are not of concern. The following is a summary of the 

occupational handler combined risk estimates:

 For mixers/loaders/applicators (MLAs) of liquids using an injector for termiticide 

applications, combined MOEs were above the LOC of 100 at baseline (single layer of 

clothing, no gloves, no respirator).
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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 For MLAs of liquids using a backpack or manually-pressurized handwand for 

applications to greenhouse ornamentals, combined MOEs were above the LOC of 100 at 

baseline.

 For applicators using ready-to-use aerosol cans, combined MOEs were above the LOC of 

100 with a single layer of clothing and gloves, but no respirator.

 For MLAs of liquid using a manually-pressurized handwand for application to 

greenhouse vegetables, combined MOEs were above the LOC of 100 with a single layer 

of clothing and gloves, but no respirator.

 For MLAs of liquids using a manually-pressurized handwand for applications to indoor 

environments such as food handling establishments, warehouses, and residential living 

spaces, combined MOEs were above the LOC of 100 with a single layer of clothing, 

gloves and a PF5 respirator.

 For mixers/loaders/applicators of liquids using a mechanically-pressurized handgun for 

termiticide applications to structures, combined MOEs were above the LOC of 100 with a 

single layer of clothing, gloves and a PF5 respirator.

 For mixers/loaders/applicators of liquids using a mechanically-pressurized handgun for 

greenhouse applications, combined MOEs did not reach the LOC of 100 even with 

maximum PPE (i.e., double layer, gloves and PF10 respirator).

 
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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Table 9.1.1. Occupational Handler Non-Cancer Exposure and Risk Estimates for Chlorfenapyr.

Exposure 

Scenario Crop or Target

Dermal Unit 

Exposure (μg/lb 

ai)1

Inhalation

Unit Exposure 

(μg/lb ai)1 Maximum

Application 

Rate2

Area 

Treated or 

Amount 

Handled 

Daily3

Dermal Inhalation Total

Mitigation Level

(Baseline unless 

specified)

Mitigation Level

(Baseline unless 

specified)

Dose4

(mg/kg/day) MOE5 Dose6(mg/kg/day) MOE7 MOE8

Mixer/Loader/Applicator

Injector 

(termiticide) Structural (termiticide) 1,300 2 0.0234 lb ai/gal 124 gal9 0.0071 700 0.0000925 54,000 690

 Backpack

Greenhouse (ornamentals) 13,200 140 0.0016 lb ai/gal 40 gal 0.00159 3,100 0.00013 38,000 2,900

Greenhouse (fruiting vegetables) 13,200 140 0.04 lb ai/gal 40 gal 0.0390 130 0.00325 1,500 120

ManuallyPressurized 

Handwand

Greenhouse (ornamentals) 100,000 30 0.0016 lb ai/gal 40 gal 0.0121 410 0.0000278 180,000 410

Greenhouse (fruiting vegetables) 100,000 30 0.04 lb ai/gal

40 gal

0.301 17 0.000696 7,200 17

430 (SL with G) 0.0013 3,800 2,500 

Crack and crevice – residential 

living spaces, food handling 

establishments, warehouses

29,000

1,100

0.05 lb ai/gal

0.109 46

0.0319 160

36

8,600 (SL with G) 0.0324 150

77

220 (PF5 R) 0.00638 780 150

MechanicallyPressurized 

Handgun

Greenhouse (ornamentals) 3,500 120 0.0016 lb ai/gal 1000 gal 0.0106 470 0.00278 1,800 370

Greenhouse (fruiting vegetables)

3,500 120

0.04 lb ai/gal 1000 gal

0.264 19 0.0696 72 15

2,500 (SL with G) 24 (PF5R) 0.188 27 0.0139 360 20

1,600 (DL with G) 12 (PF10R) 0.121 41 0.00696 720 26

Structural (termiticide)

1,800

79 0.0234 lb ai/gal 1000 gal

0.0793 63

0.0268 190

47

640 (SL with G) 0.0283 180 92

365 (DL with G) 0.0161 310 120

Applicator

Ready-to-use 

Aerosol cans Crack and crevice (termiticide) 190,000 1,300 0.005 lb ai/can 20 cans 0.0358 140 0.00188 2,700 130

Bolded values are below the LOC of 100.

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

2 Based on all registered labels (See Appendix D).

3 Exposure Science Advisory Council Policy #9.1.

4 Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/gal or can) × Amount Handled Daily (gal or can/day) × DAF (13%) ÷ BW (69 kg).

5 Dermal MOE = Dermal NOAEL (5 mg/kg/day) ÷ Dermal Dose (mg/kg/day).

6 Inhalation Dose = Inhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/gal or can) × Amount Handled Daily (gal or can/day) ÷ BW (69 kg).

7 Inhalation MOE = Inhalation NOAEL (5 mg/kg/day) ÷ Inhalation Dose (mg/kg/day). 

8 Total MOE = 1 ÷ (1/Dermal MOE) + (1/Inhalation MOE)

9 The unit treated for injector are from Memo D. Smegal and T. Leighton, 20 June 2000, D266562 indicates an average of 124 gallons per residence for termiticide treatments.
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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9.2 Occupational Post-Application Exposure

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

9.2.1 Occupational Post-application Inhalation Exposure/Risk Estimates

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

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

inhalation toxicity (Toxicity Category III), low vapor pressure (1.0 x 10-7 mm Hg @ 25 ̊C), and 

the low registered use rate (0.04-0.2 lb ai/A). However, 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 FIFRA Scientific 

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

20104. The Agency is in the process of evaluating the SAP report as well as available postapplication inhalation exposure data generated by the Agricultural Reentry Task Force (ARTF)

and may, as appropriate, develop policies and procedures, to identify the need for and, 

subsequently, the way to incorporate occupational post-application inhalation exposure into the 

Agency's risk assessments. If new policies or procedures are put into place, then the Agency 

may revisit the need for a quantitative occupational post-application inhalation exposure 

assessment for chlorfenapyr.

The Worker Protection Standard for Agricultural Pesticides contains requirements for protecting 

workers from inhalation exposures during and after greenhouse applications through the use of 

ventilation requirements [40 CFR §170.110, (3) (Restrictions associated with pesticide 

applications)].

Commercial applicators do not typically return to the treated areas after an indoor commercial 

pesticide application (sites such as warehouses, food handling establishments, and hotels, etc.) 

and thus an occupational post-application inhalation exposure assessment was not performed for 

commercial applicators.

9.2.2 Occupational Post-application Dermal Exposure/Risk Estimates

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

post-application risk assessments. Each assumption and factor is detailed in the most recent 

 

4 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html
Chlorfenapyr Preliminary Human Health Risk Assessment D416560

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ORE memo (L. Venkateshwara; 8-MAY-2014; D417598). The algorithms used to estimate noncancer exposure and dose for occupational post-application workers can be found in Appendix C.

The short- and intermediate-term post-application exposure scenarios associated with the 

registered uses of chlorfenapyr are summarized in Table 9.2.2.1. All scenarios resulted in MOEs 

greater than the LOC of 100 (ranging from 120 to 2,600) on day 0 (12 hours after application) 

and, therefore, are not of concern to HED.

Table 9.2.2.1. Occupational Post-application Non-Cancer Exposure and Risk Estimates for Chlorfenapyr.

Crop/Site Activities

Transfer 

Coefficient 

(cm2/hr)

DFR/TTR1 Dermal Dose 

(mg/kg/day)2 MOE3

Short and Intermediate-Term

Floriculture Crop 

(cut flowers)

Container Moving, Pinching, Hand 

Pruning, Hand Weeding, Scouting, 

Transplanting, 

230

0.56

0.002 2,600

Irrigation (hand set) 1,900 0.016 310

Hand Harvesting 4,800 0.041 120

Greenhouse Vegetables

Transplanting, Irrigation (hand 

watering) 230 0.002 2,600

Hand harvesting, Pinching, 

Pollination, Hand Pruning, 

Scouting, Turing, Tying/training, 

Hand Weeding, Propagating, Hand 

Pruning, Scouting

1200 0.010 490

Greenhouse 

Ornamental, Nonbearing Plant

Hand harvesting, Hand Pruning, 

Scouting, Container Moving, Hand 

Weeding, Transplanting, Pinching, 

Tying/Training, Grafting, 

Propagating

230 0.002 2,600

1 DFR = Application Rate × F × (1-D)t × 4.54E8 μg/lb × 2.47E-8 acre/cm2; where F = 0.25 and D = 0.10 per day 

2 Daily Dermal Dose = [DFR (μg/cm2) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption (13%)]  BW (69 kg).

3 MOE = POD (5 mg/kg/day) / Daily Dermal Dose. Daily Dermal Dose = [DFR (μg/cm2) × TC × 0.001 mg/μg × 8 hrs/day × dermal 

absorption factor (13 %)]  BW 69 kg).

Restricted Entry Interval

The REIs specified on existing labels are based on the acute toxicity of chlorfenapyr. 

Chlorfenapyr is classified as Toxicity Category III or IV via the dermal route and skin irritation 

potential. It is not a skin sensitizer. Under 40 CFR 156.208 (c) (2) (iii), active ingredients

classified as Acute III or IV for acute dermal, eye irritation, and primary skin irrigation are 

assigned a 12-hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim 

REI of 12 hours on the currently registered labels is adequate to protect agricultural workers 

from post-application exposures to chlorfenapyr. 
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10.0 References

Recent RA

G. Kramer, et al., 10-MAR-2003; D275052

Scoping Document

A. Dunbar; 26-MAY-2010; D373133

HASPOC Memo

U. Habiba, 07-JUN-2013, TXR# 0056692

ORE Memo

L. Venkateshwara, 8-MAY-2014, D417598

Dietary Memo

W. Wassell, 20-MAY-2014, D417599

cc: M. Perron, W. Wassell, L. Venkateshwara

RDI: RAB1 (22-MAY-2014) 

M.M. Perron:S10955:PY-S:(703)347-0395:7509P:RAB1
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Appendix A. Toxicology Profile 

A.1 Toxicology Data Requirements

Study requirements (40 CFR 158.340) for chlorfenapyr are presented below. Use of the new 

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

Study

Technical

Required Satisfied

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

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

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

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

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

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

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 90-Day Oral Toxicity (rodent) ......................................

870.3150 90-Day Oral Toxicity (nonrodent) ................................

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

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

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

yes

yes

yes

no

yes

yes

yes

yes

--

yes

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

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

870.3800 Reproduction and Fertility Effects ................................

yes

yes

yes

yes

yes

yes

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

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

870.4200a Carcinogenicity (rat)......................................................

870.4200b Carcinogenicity (mouse) ...............................................

870.4300 Combined Chronic Toxicity/Carcinogenicity ...............

yes

yes

yes

yes

yes

yes1

yes

yes1

yes

yes

870.5100 Mutagenicity—Bacterial Reverse Mutation Test..........

870.5300 Mutagenicity—Mammalian Cell Gene Mutation Test..

870.5xxx Mutagenicity— Structural Chromosomal Aberrations..

870.5xxx Mutagenicity—Other Genotoxic Effects.......................

yes

yes

yes

yes

yes

yes

yes

yes

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

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

870.6300 Developmental Neurotoxicity .......................................

yes

yes

yes

yes

yes2

yes

870.7485 Metabolism and Pharmacokinetics................................

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

870.7800 Immunotoxicity .............................................................

yes

no

no3

yes

--

--

1

 The combined chronic toxicity/carcinogenicity study satisfies the requirement of the study. 

2

 A chronic neurotoxicity study was performed and fulfills the requirement for a subchronic neurotoxicity study.

3

 HED HASPOC concluded that the immunotoxicity study was not required at this time (U. Habiba, 07-JUN-2013; 

TXR#0056692). 
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A.2 Toxicity Profiles

Table A.2.1. Acute Toxicity Profile – Chlorfenapyr.

Guideline 

No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral (rat) 42770207

42884201

441 mg/kg, males

1152 mg/kg, females

626 mg/kg, combined

II*

870.1200 Acute dermal (rabbit) 42770208 >2000 mg/kg III

870.1300 Acute inhalation (rat) 42770209

0.83 mg/L, males

>2.7 mg/L, females

1.9 mg/L, combined 

III

870.2400 Acute eye irritation (rabbit) 42770210

Corneal opacity, iritis, 

and conjunctivitis 

present at 48 hours. All 

rabbits normal by Day 7.

III

870.2500 Acute dermal irritation (rabbit) 42770211 Non-irritating IV

870.2600 Skin sensitization (guinea pig) 42770212 Non-sensitizer Not applicable

*Based on most sensitive sex

Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile - Chlorfenapyr.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3100 90-Day Oral 

Toxicity in Rodents 

(rat)

42770219 (1993)

Acceptable/guideline

0, 150, 300, 600, 900, 1200 

ppm

0, 11.7, 24.1, 48.4, 72.5, 94.5 

mg/kg/day

NOAEL =24.1 mg/kg/day.

LOAEL = 48.4 mg/kg/day based on spongiform 

myelopathy in the brain and spinal cord of male 

rats, and increased liver weight in males and 

females, increased absolute liver weight in females 

and decreased hemoglobin in females.

870.3100 90-Day Oral 

Toxicity in Rodents 

(mouse)

43492830 (1994)

Acceptable/guideline

0, 40, 80, 160, 320 ppm

M: 0, 7.1, 14.8, 27.6, 62.6 

mg/kg/day

F: 0, 9.2, 19.3, 40, 78 

mg/kg/day

NOAEL = 14.8/19.3 mg/kg/day (M/F).

LOAEL = 27.6/40.0 mg/kg/day (M/F) based on 

increased spleen weights (absolute and relative).

Spongiform encephalopathy and significant changes 

in blood chemistry observed in both sexes at the 

HDT.

870.3150 90-Day Oral 

Toxicity in NonRodent (dog)

42770220 (1993)

Acceptable/guideline

0, 60, 120, ~247* ppm

M: 0, 2.1, 3.9, 6.7 mg/kg/day

F: 0, 2.2, 4.5, 6.8 mg/kg/day

*high dose animals received 

300 ppm during days 1-15, 

240 ppm during days 15-25 

and 200 ppm during days 25-

93

NOAEL = 6.7/6.8 mg/kg/day (M/F).

LOAEL not established.
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile - Chlorfenapyr.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.3200 28-Day Dermal 

Toxicity (rat)

46654702 (2005)

Acceptable/guideline

0, 100, 300, 1000 ppm

0, 72.1, 205.5, 835 mg/kg/day

NOAEL = 205.5 mg/kg/day.

LOAEL = 835 mg/kg/day based on clinical signs 

consisting of slight to moderate urine smearing of 

the anogenital region for several days in female rats 

and liver weight increases (absolute and relative) in 

both sexes.

870.3465 90-Day Inhalation 

Study (rat)

46654701 (2005)

Acceptable/guideline

0, 5, 20, 40, 80 mg/m3

NOAEL = 20 mg/m3.

LOAEL = 40 mg/m3 based on visually accelerated 

respiration, increased white blood cell and 

lymphocyte counts, and changes in clinical 

parameters in both sexes.

Mortality observed in males at 80 mg/m3.

870.3700a Prenatal 

Developmental in 

Rodent (rat)

42884202 (1993)

0, 25, 75, 225 mg/kg/day

Maternal NOAEL = 225 mg/kg/day.

Maternal LOAEL not established.

Developmental NOAEL = 225 mg/kg/day.

Developmental LOAEL not established.

870.3700b Prenatal 

Developmental in 

Non-Rodent (rabbit)

42770222 (1993)

0, 5, 15, 30 mg/kg/day

Maternal NOAEL = 30 mg/kg/day.

Maternal LOAEL not established.

Developmental NOAEL = 30 mg/kg/day.

Developmental LOAEL not established.

870.3800 Reproduction and 

Fertility Effects (rat)

43492836 (1994)

Acceptable/guideline

0, 60, 300, 600 ppm

M: 0, 4.5, 22.2, 44.0 

mg/kg/day

F: 0, 5.0, 24.5, 48.3 

mg/kg/day

Parental NOAEL = 22.2/24.5 mg/kg/day (M/F).

Parental LOAEL = 44.0/48.3 mg/kg/day (M/F) 

based on decreased body-weight.

Offspring NOAEL = 4.5/5.0 mg/kg/day (M/F).

Offspring LOAEL = 22.2/24.5 mg/kg/day (M/F) 

based on decreased pup weights. 

Pup deaths were considered adverse at the highdose in the F2 generation.

Reproductive NOAEL=44.0/48.3 mg/kg/day (M/F).

Reproductive LOAEL not established.

870.4100a Chronic Toxicity

(rodent) See 870.4300 See 870.4300

870.4100b Chronic Toxicity

(dog)

43492834 (1194)

Acceptable/guideline

0, 60, 120, 240 ppm

M: 0, 2.1, 4.0, 8.7 mg/kg/day

F: 0, 2.3, 4.5, 10.1 mg/kg/day

NOAEL = 4.0/4.5 mg/kg/day (M/F).

LOAEL = 8.7/10.1 mg/kg/day (M/F) based on 

decreased body-weight.

870.4200a Carcinogenicity (rat) See 870.4300 See 870.4300
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile - Chlorfenapyr.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.4200b Carcinogenicity 

(mouse)

43492838 (1994)

Acceptable/guideline

0, 20, 120, 240 ppm

M: 0, 2.8, 16.6, 34.5 

mg/kg/day

F: 0, 3.7, 21.9, 44.5 

mg/kg/day

NOAEL = 2.8/3.7 mg/kg/day (M/F).

LOAEL = 16.6/21.9 mg/kg/day (M/F) based on

brain vacuolation and scabbing of the skin (males).

No evidence of carcinogenicity.

870.4300 Combined Chronic 

Toxicity/

Carcinogenicity (rat)

43492837 (1994)

Acceptable/guideline

0, 60, 300, 600 ppm

M: 0, 2.9, 15.0, 30.8 

mg/kg/day

F: 0, 3.6, 18.6, 37.0 

mg/kg/day

NOAEL = 15 mg/kg/day (males).

LOAEL = 30.8 mg/kg/day based on anemia in 

males.

NOAEL = 3.6 mg/kg/day (females).

LOAEL = 18.6 mg/kg/day based on decreased 

body-weight in females.

Classification: “Suggestive Evidence of 

Carcinogenicity, but Not Sufficient to Assess 

Human Carcinogenic Potential” based on 

significant trends in liver tumors (adenomas and 

combined adenomas/carcinomas), malignant 

histiocytic sarcomas, and testicular cell tumors in 

male rats and uterine polyps in female rats seen at 

the highest dose.

870.5100 Bacterial reverse 

mutation

42770223 (1993)

Acceptable/guideline

Negative for reverse mutation in S. typhimurium 

strains TA 98, TA 100, TA 1535, TA 1537, TA 

1538 and E. coli strain WP2 uvrA – exposed up to 

cytotoxicity (50 μg/plate, +/- S9).

870.5300 In vitro mammalian 

cell gene mutation

42770224, 43187601 (1993)

Acceptable/guideline

Independently performed tests were negative up to 

a cytotoxic and precipitating concentration (500 

μg/mL) in the presence of S9 activation or the 

solubility limit (250 μg/mL) without S9 activation.

870.5375 In vitro mammalian 

chromosome 

aberration

43492843 (1994)

Acceptable/guideline

The test was negative up to 100 μg/mL –S9 or 25 

μg/mL +S9; higher doses with or without S9 

activation were cytotoxic.

870.5385 In vitro chromosome 

aberration assay in 

Chinese hamster 

lung cells

43492839 (1994)

Acceptable/guideline

The test was negative up to a precipitating level 

without S9 activation (225 μg/mL) or a 

concentration range of 3.5-14.1 μg/mL +S9. Higher 

S9-activated doses (≥28 μg/mL) were cytotoxic.

870.5395 Mammalian 

micronucleus 

(mouse)

42770225, 43187602

(1993, 1994)

Acceptable/guideline

The test was negative in mice administered single 

oral gavage doses of 7.5-30 mg/kg (males) or 5-20 

mg/kg (females). Clinical toxicity (deaths in males 

and diarrhea in females) was seen at the highest 

dose tested. There was however no evidence of 

cytotoxicity for the target organ.

870.5550 Unscheduled DNA 

synthesis

42770226 (1993)

Acceptable/guideline

Negative for inducing unscheduled DNA synthesis 

in primary rat hepatocyte cultures exposed up to 

severely toxic concentrations (≥30 μg/mL).

870.6200a Acute Neurotoxicity 

Screening Battery 

(rat)

43492829 (1994)

Acceptable/guideline

0, 45, 90, 180 mg/kg

NOAEL = not established.

LOAEL = 45 mg/kg/day based on decreased motor 

activity on day of dosing.
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Table A.2.2. Subchronic, Chronic, and Other Toxicity Profile - Chlorfenapyr.

Guideline 

No. Study Type

MRID No. (year)/ 

Classification /Doses Results

870.6200b Chronic

Neurotoxicity 

Screening Battery 

(rat)

43492833 (1994)

Acceptable/guideline

0, 60, 300, 600 ppm

M: 0, 2.6, 13.6, 28.2 

mg/kg/day

F: 0, 3.4, 18.0, 37.4 

mg/kg/day

NOAEL = 2.6/3.4 mg/kg/day (M/F).

LOAEL = 13.6/18.0 mg/kg/day (M/F) based on the 

presence of alterations in the myelin of the CNS in 

male rats, decreased body-weight, food efficiency, 

absolute food consumption (females) and water 

consumption (males).

870.6300 Developmental 

Neurotoxicity Study

(rat)

46740201 (2006)

Acceptable/non-guideline

0, 5, 10, 15 mg/kg/day

Maternal NOAEL = 15 mg/kg/day.

Maternal LOAEL not established.

Developmental NOAEL = 5 mg/kg/day.

Developmental LOAEL = 10 mg/kg/day based on 

increased pup deaths and decreased motor activity.

At high dose, vacuolation of the white matter and 

decreased hippocampus size were observed in 

several areas of the brain at PND 22.

Classified as non-guideline pending positive control 

data.

870.7485 Metabolism and 

Pharmacokinetics

(rat)

43492844 (1994)

Acceptable/guideline

20, 200 mg/kg/day

Low recoveries of the radioactive dose in urine and 

tissues indicated limited absorption. More than 

80% of the doses were eliminated in the feces. 

Most of the radioactivity was eliminated in the 

feces and urine within 48 hours of dosing. After 7 

days, 89-121% of the dosed radioactivity was 

recovered. At sacrifice, female rats had greater 

recovery (about twice) in the carcass, blood, and fat 

at all doses than did males. The highest recovery of 

radioactivity from a single organ was from the liver 

(0.15-0.48% of dose). Parent compound was the 

major component found in excreta (40-70% of 

administered doses). Based on the metabolites 

identified, the major deposition route of orally 

administered chlorfenapyr is fecal excretion of 

unaltered parent compound. Metabolites are 

minimally accumulated in tissue and excreted 

primarily in urine.

870.7600 In vivo dermal 

penetration

(rat)

49315901 (2005)

Acceptable/guideline 

Formulation concentrate (BAS 

306 02 I) at 2.4 mg/cm2and 

0.0217 mg/cm2

At 8, 24, and 120 hours, dermal absorption (tissues, 

excreta, surrounding skin, and application site) for 

the 2.4 mg/cm2 dose was 6.4%, 3.9%, and 3.6%, 

respectively.

At 8, 24, and 120 hours, dermal absorption (tissues,

excreta, surrounding skin, and application site) for 

the 0.0217 mg/cm2 dose was 13.1%, 10.7%, and 

15.1%, respectively.
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Appendix B. Physical/Chemical Properties

Table B.1. Physical and Chemical Properties for Chlorfenapyr.

Parameter Value Reference

Color light tan or light yellow

Memo, G. 

Kramer et al., 12-

FEB-1998; 

D221320

Physical State powdered solid

Odor characteristic of halides and ketones

Melting Point melting point apparatus 100-101 C

Boiling Point n/a; technical grade of the active ingredient (TGAI) is a 

solid

Density, Bulk Density, or 

Specific Gravity

0.543 g/mL tapped bulk density 0.355 g/mL untapped bulk 

density

Solubility

 Solvent Solubility at 25oC

deionized water 0.12 mg/L

water, pH 4 0.13 mg/L

water, pH 7 0.14 mg/L

water, pH 10 0.12 mg/L

hexane 0.89 g/100 mL

methanol 7.09 g/100 mL

acetonitrile 68.4 g/100 mL

toluene 75.4 g/100 mL

acetone 114 g/100 mL

dichloromethane 141 g/100 mL

Vapor Pressure <1.0 x 10-7 mm Hg at 25C

Dissociation Constant since there are no ionizable groups in the chlorfenapyr 

structure, no dissociation will occur (PAI)

Octanol/Water Partition 

Coefficient Kow = 67,670 (log Kow = 4.83) at 25C

pH 7.16; 1% aqueous slurry at 24C
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Appendix C: Summary of Occupational and Residential Algorithms 

Occupational Non-cancer Handler Algorithms

Potential daily exposures for occupational handlers are calculated using the following formulas:

E=UE * AR * A * 0.001 mg/ug

where:

E = exposure (mg ai/day),

UE = unit exposure (μg ai/lb ai),

AR = maximum application rate according to label (lb ai A or lb ai/gal), and

A = area treated or amount handled (e.g., A/day, gal/day).

The daily doses are calculated using the following formula:

ADD= 

E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = exposure (mg ai/day),

AF = absorption factor (dermal and/or inhalation), and

BW = body-weight (kg).

Margin of Exposure: Non-cancer risk estimates for each application handler scenario are 

calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to 

the daily dose of concern. The daily dermal and inhalation dose received by occupational 

handlers are compared to the appropriate POD (i.e., NOAEL) to assess the risk to occupational 

handlers for each exposure route. All MOE values are calculated using the following formula:

MOE= 

POD

ADD

where:

MOE = margin of exposure: value used by HED to represent risk estimates (unitless),

POD = point of departure (mg/kg/day), and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).

Occupational Non-cancer Post-application Algorithms

Potential daily exposures for occupational post-application workers are calculated using the 

following formulas:

DFRt=AR * F* (1-D)t* (4.54E8

ug

lb) * (2.47E-8

A

cm2

)
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where:

DFRt = dislodgeable foliage residue on day "t" (μg/cm2),

AR = application rate (lb ai/acre),

F = fraction of ai retained on foliage or 25% (unitless),

D = fraction of residue that dissipates daily or 10% (unitless), and

t = number of days after application day (days).

E=TC * DFR t* ET * 0.001

mg

ug

where:

E = exposure (mg ai/day),

TC = transfer coefficient (cm2/hr),

DFRt = dislodgeable foliar residue on day “t” (μg/cm2), and

ET = exposure time (hours/day).

The daily doses are calculated using the following formula:

ADD= 

E * AF

BW

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = exposure (mg ai/day),

AF = absorption factor (dermal and/or inhalation), and

BW = body-weight (kg).

Margin of Exposure: Non-cancer risk estimates for each scenario are calculated using a MOE, 

which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal dose 

received by occupational post-application workers is compared to the appropriate POD (i.e.,

NOAEL) to assess the risk to occupational post-application workers. All MOE values are 

calculated using the following formula:

MOE= 

POD

ADD

where:

MOE = margin of exposure: value used by HED to represent risk estimates (unitless),

POD = point of departure (mg/kg/day), and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).

Residential Non-cancer Handler Algorithms

Residential Non-cancer Post-application Algorithms

Exposure to pesticide vapors 
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The following algorithm is used to determine post-application inhalation exposure from indoor 

surface-directed sprays:

E =

IR ∗ Mlabel

ACH ∗ Vroom [1 − (

(ACH ∗ e

−k∗ET) − (k ∗ e−ACH∗ET

ACH − k

)]

where:

E = exposure (mg/day);

IR = inhalation rate (m3/hr);

Mlabel = mass of active ingredient applied, determined from product label (mg);

Vroom = volume of room (m3);

ACH = air exchanges per hour (1/hr);

k = first order decay rate (1/hr); and

ET = exposure time (hr).

In the above equation, a mass of pesticide is applied to a surface and the emission of the 

pesticide from the surface is assumed to decline over time due to dissipation of the pesticide (i.e., 

emission from the treated surface and removal due to the air exchange rate). The mass of active 

ingredient applied can be calculated using the following formula:

Mlabel = AR ∗ A ∗ CF1

where:

Mlabel = mass of active ingredient applied, determined from product label (mg);

AR = application rate (e.g., lb ai/ft2, lb ai/gal); 

A = area treated or amount handled (e.g., ft2/day, gal/day); and

CF1 = conversion factor (4.54x105 mg/lb).

The exposure equation models an emission rate that decreases over time, which is based on a 

first-order decay rate constant (k). Evans (1994) proposed calculating such a decay rate based on 

work done by Chinn (1981). Chinn developed the following relationship between the volatility, 

or saturation concentration (Csat), of a chemical and the time required for 90% of the chemical to 

evaporate (EvapT): 

EvapT = 10[7.3698−0.9546∗ log10(Csat)]

where:

EvapT = evaporation time (sec); and

Csat = saturation concentration (mg/m3).

Evans proposed the following equation to calculate the decay rate (or dissipation rate) that 

defines the change in the emission rate based on the evaporation time described by Chinn:

k =

ln(0.1) ∗ CF1

EvapT
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where:

k = first order decay rate (1/hr),

CF1 = conversion factor (sec/hr), and

EvapT = evaporation time (sec).

The exposure equation above is based on the mass of pesticide applied, not the concentration of 

the pesticide in the air; therefore, the reviewer must check that the input for mass applied (Mlabel) 

is predicting an air concentration less than or equal to the saturation concentration. The 

following equation can be used to calculate the theoretical mass applied that would result in an 

air concentration that reaches the saturation concentration for a pesticide (MCsat): 

MCsat =

Csat ∗ (ACH − k) ∗ V

k

MCsat should be compared to Mlabel. 

 If Mlabel > MCsat  Mlabel will predict an air concentration higher than the saturation 

concentration. Use MCsat in the exposure calculation. 

 If Mlabel < MCsat,  Mlabel will not predict an air concentration higher than the saturation 

concentration. Use Mlabel in the exposure calculation. 

Once the post-application inhalation exposure is calculated, the inhalation dose normalized to 

body-weight is calculated as:

D =

E ∗ AF

BW

where:

D = dose (mg/kg-day);

E = exposure (mg/day);

AF = absorption factor (inhalation); and

BW = body-weight (kg).

Table C.1. Indoor Environments – Inputs for Residential Post-application Inhalation Exposure.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

Generic Variables Used in Calculating Post-application Inhalation Exposure

IR Inhalation rate 

(m3/hour)

Adult 0.64

Children 1 < 2 years old 0.33

ACH Air changes per hour 

(hr-1)

0.45

BW Body-weight

(kg)

Adult 69

Children 1 < 2 years old 11

Vroom

Volume of room 

(m3)

33

Variables Specific to Post-application Inhalation Exposure to Pesticide Vapors
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Table C.1. Indoor Environments – Inputs for Residential Post-application Inhalation Exposure.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

Csat

Saturation concentration

(mg/m3)

Calculated

VP Vapor pressure 

(mmHg) 1.0 x 10-7 mm HG @ 25 ̊C

MW Molecular weight 

(g/mol) 407.6

R

Gas constant 

(L-atm/mol-K) 0.0821 

T

Temperature of the air

(kelvin, K) 298

Mlabel

Mass of active ingredient applied 

(mg) [input]

k First order decay rate Calculated

ET Exposure time 

(hr./day)

Adult 16

Children 1 < 2 years old 18

Post-Application Dermal Exposure Algorithm (hard surfaces and carpets)

The algorithm to calculate exposure is as follows:

E = TR ∗ TC ∗ ET ∗ CF1

where:

E = exposure (mg/day);

TR = indoor surface transferable residue (μg/cm2);

TC = transfer coefficient (cm2/hr); 

ET = exposure time (hr/day); and

CF1 = conversion factor (0.001 mg/μg).

If chemical-specific TR data are available, this is preferred and should be used to calculate 

exposure. However, if chemical-specific TR data are not available, then TR can be calculated 

using the following formula:

TR = DepR ∗ Fai

where:

TR = indoor surface transferable residue (μg/cm2);

DepR = deposited residue (g/cm2), based on (in order of preference):

(1) Chemical-specific residue deposition data (g/cm2),

(2) Application rate (lb ai/area), or

(3) Default residue based on type of application (g/cm2); and

Fai = fraction of ai available for transfer from carpet or hard surface (unitless).

Absorbed dermal dose, normalized to body-weight, are calculated as:

D =

E ∗ AF

BW
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where:

D = dose (mg/kg-day);

E = exposure (mg/day);

AF = absorption factor; and

BW = body-weight (kg).

Table C.2. Indoor Environments (Hard Surfaces and Carpets) – Inputs for Residential Post-application Dermal 

Exposure.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

TR Transferable residue

(g/cm2)

-Estimated: DepR * Fai

DepR Deposited residue

(g/cm2)

-Estimated based on default residue 

related to type of application

Fai

Fraction of DepR as TR 

following application

Carpets 0.06a

Hard surfaces 0.08a

TC Transfer Coefficient

(cm2/hr)

Adult 6,800

Children 1 < 2 years old 1,800

ET Exposure Time (hrs/day)

Adults

Carpets 8

Hard 

Surfaces 2

Children 1 < 2 

years old

Carpets 4

Hard 

Surfaces 2

BW Body-weight (kg) Adult 69

Children 1 < 2 years old 11

Post-Application Dermal Exposure Algorithm (mattresses)

The algorithm to calculate absorbed dose is as follows:

D = DR ∗

SA

BW ∗ F ∗ Fai ∗ PF ∗ AF ∗ CF1

where:

D = Dermal dose (mg/kg-day);

DR = Deposited residue (mg/cm2);

SA/BW = Surface area / Body-Weight Ratio (cm2/kg);

F = Fraction of body that contacts residue;

CF1 = Conversion factor (mg/g);

AF = Absorption factor;

Fai = fraction of ai available for transfer from treated mattress; and

PF = Protection factor to account for the presence of a single layer of 

fabric (e.g. bed sheet) between the treated material and individual.

Table C.3. Indoor Environments (mattresses) – Inputs for Residential Post-application Dermal Exposure.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

DR Deposited residue

(g/cm2)

Based on default residue values
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Table C.3. Indoor Environments (mattresses) – Inputs for Residential Post-application Dermal Exposure.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

SA/BW

Surface area / Body-Weight 

Ratio

(cm2/kg)

Adult 280

Children 1 < 2 

years old 640

F Fraction of body that contacts residue 0.5

Fai Fraction of DR available for transfer 0.06

PF Protection Factor 0.5

Post-application Hand-to-Mouth Exposure Algorithm

Exposure from hand-to-mouth activity is calculated as follows (based on algorithm utilized in 

SHEDS-Multimedia):

E = [HR ∗ (FM ∗ SAH) ∗ (ET ∗ N_Replen) ∗ (1 − (1 − SE)

Freq_HtM

N_Replen )]

where:

E = exposure (mg/day);

HR = hand residue loading (mg/cm2);

FM = fraction hand surface area mouthed / event (fraction/event);

ET = exposure time (hr/day);

SAH = surface area of one hand (cm2);

N_Replen = number of replenishment intervals per hour (intervals/hour);

SE = saliva extraction factor (i.e., mouthing removal efficiency); and

Freq_HtM = number of hand-to-mouth contacts events per hour (events/hour).

and

HR =

Faihands ∗ DE

SAH ∗ 2

where:

HR = hand residue loading (mg/cm2);

Faihands = fraction ai on hands compared to total surface residue from jazzercise 

study (unitless);

DE = dermal exposure (mg); and

SAH = typical surface area of one hand (cm2).

and

Dose, normalized to body-weight, is calculated as:
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D =

E

BW

where:

D = dose (mg/kg-day);

E = exposure (mg/day); and

BW = body-weight (kg).

Table C.4. Indoor Environments – Inputs for Residential Post-application Hand-to-Mouth Exposure.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

Faihands

Fraction of ai on hands from jazzercise study

(unitless) 0.15

DE Dermal exposure calculated in Section 5.2.2 (mg) Calculated

HR Residue available on the hands 

(mg/cm2)

Calculated

SAH Surface area of one hand (cm2) Children 1 < 2 years old 150

AR Application rate

(mass active ingredient per unit area) 11,350

FM

Fraction of hand mouthed per event 

(fraction/event) 0.13

N_Replen Replenishment intervals per hour

(intervals/hr) 4

ET Exposure time

(hours per day)

Children 1 < 2 

years old

Carpets 4

Hard Surfaces 2

SE Saliva extraction factor

(fraction) 0.48

Freq_HtM

Hand-to-mouth events 

per hour

(events/hr)

Children 1 < 2 years old 20

BW Body-Weight

(kg) Children 1 < 2 years old 11

Post-application Object-to-Mouth Exposure Algorithm

Exposure from object-to-mouth activity is calculated as follows (based on algorithm utilized in 

SHEDS-Multimedia):

E = OR ∗ CF1 ∗ SAMO ∗ (ET ∗ N_Replen) ∗ (1 − (1 − SE)

Freq_OtM

N_Replen )

where:

E = exposure (mg/day);

OR = chemical residue loading on an object (g/cm2);

CF1 = weight unit conversion factor (0.001 mg/g);

SAMO = area of the object surface that is mouthed (cm2/event);
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ET = exposure time (hr/day);

N_Replen = number of replenishment intervals per hour (intervals/hour);

SE = saliva extraction factor (i.e., mouthing removal efficiency); and

Freq_OtM = number of object-to-mouth contact events per hour (events/hour).

and

OR = DepR ∗ FO

where:

OR = chemical residue loading on the object (μg/cm2);

DepR = deposited residue (μg/cm2); and

FO = fraction of residue transferred to an object (unitless).

and

Oral dose, normalized to body-weight, is calculated as:

D =

E

BW

where:

D = dose (mg/kg-day);

E = exposure (mg/day); and

BW = body-weight (kg).

Table C.5. Indoor Environments – Inputs for Residential Post-application Object-to-Mouth Exposure.

Algorithm 

Notation

Exposure Factor

(units) Point Estimate(s)

AR Application rate

(mass active ingredient per unit area) input

FO

Fraction of residue 

transferred to an object

Carpets 0.06a

Hard surfaces 0.08a

SAMO

Surface area of object mouthed

(cm2/event) 10

N_Replen Replenishment intervals per hour

(intervals/hour) 4

SEO Saliva extraction factor 0.48

ET Exposure Time

(hours per day)

Children 1 < 

2 years old

Carpets 4

Hard Surfaces 2

Freq_OtM

Object-to-mouth events 

per hour

(events/hour)

Children 1 < 2 years old 14

BW Body-Weight

(kg) Children 1 < 2 years old 11
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Appendix D. Registered Chlorfenapyr End-Use Products

Table D.1. Registered Chlorfenapyr End-Use Products.

EPA Reg. No. Formulation 

Type

Product Label Name Company

241-366 -- Chlorfenapyr Technical BASF Corporation

241-374 EC Pylon® Miticide-Insecticide BASF Corporation

241-392 EC Phantom Termiticide Insecticide BASF Corporation

499-544 PRL TC-307 Whitmire Micro-Gen Research 

Laboratories, Inc

499-548 PRL TC-314 Whitmire Micro-Gen Research 

Laboratories, Inc

499-556 PRL TC-326 Whitmire Micro-Gen Research 

Laboratories, Inc

7969-285 PRL Prescription Treatment® Brand 

Phantom® Pressurized Insecticide BASF Corporation
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Appendix E. 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, which include studies from 

the Pesticide Handlers Exposure Database (PHED) 1.1, the Agricultural Handler Exposure Task 

Force (AHETF) database, and the ARTF database 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 website5. 

 

5 http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html