### UNITED STATES ENVIRONMENTAL PROTECT I ON AGENCY
WASHIN G TON, D.C. 20460

MEMORANDUM

Date : May 22, 2014 OFF ICE OF CHEMICAL SAF E T Y AND PO LLU TION P R E VENT ION



### SUBJECT: Chlo r fenapyr- Preliminary Human Health Risk Assessment for Registration
Review

PC Code: 129093
Decision No .: 485596
Petition No.: NA DP Barcode: 04 16560 Registration No.: N/A Regulatory Action: Registration Review Risk Assessment
Case No.: 7419 Risk Assessment Ty pe : Single Chemical / Aggregate
TXRNo. : NA CAS No.: 122453-73 -0
40 CFR: §180

. 513 MRID No.: NA



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

., Toxicologist
William D. Wassell, Chemist

Lata Venkateshwara, Environmental Scientist

Risk Assessment Branch 1 (RAB 1)
Health Effec ts Di vis ion (HED; 7509P)

THROUGH: Charles W. Smith III

, 

### Branch Chief 

# c::

-- ·- =-

-- (**~** George 

### F. Kramer, Ph.D., Senior Chemist

## ~~ RAB 1/HED (7509P)

And

Ray Kent, Review 

# ':S**~** Barry O'Keefe, Reviewer 

# B. {) t 

### Risk Assessment Review Commi tte e ( 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 Registra t ion Review of chlorfenapyr ( 4-bromo-2-( 4-chlorophenyl)-1-ethoxymethyl-5-trifluoromethyl-1 H-pyrrole-3- carbonitrile). The hazard characterization, endpoint selec t ion, 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 ).

Page I of56

### 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 Ident ity

. ........................ . ................................................................................... 9
3.2 PhysicaUChem ical 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 (ADM E)

....... . .. .. .. .. .............. 

### 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 Exp osu re and Risk Estimates

..... .. .. ........................ 26

6

. 2.2 Post-application Dermal Exposure and Risk Estimates

.................... .. .. .. .. .. .. .. .. .. 27

Page 2 of 56Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 3 of 56 

### 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

................................ ................................ ................ 56Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 4 of 56 

### 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 AT P 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 (in cluding 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 l iquid 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

- MAR

2003; D275052).

This preliminary risk assessment (PRA) provides information to support the Registration Review
of chlorf enapyr 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 proce ss have been satisfied (A. Dunbar; 26

- MAY

- 2010; D373133).

Hazard Assessment : C hlorfenapyr targets the central nervous system (CNS), inducing neurohistological changes (spongiform myelinopathy of the brain and spinal cord and vacuolization of the brain, s pinal 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 w as 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 effe cts 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 r esult of chlorfenapyr ex posure. 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)

. Pa rental 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 wer e 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 Hu man Health Risk Assessment D416560

Page 5 of 56 

### Given the lack of toxicity in the r at 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 (logK OW



### = 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. Th is 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 s ufficient to assess h uman carcinogenic p otential

. ”

The chlorfenapyr risk assessment team recommends that the 10X Food Quality Protection Act
Saf ety 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 r esidues and 100% crop treated ( CT). As most tolerances f or 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 a pplications 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 chlor f enapyr to be processed. As a result, d efault processi ng 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 analyse s did not include exposure from drinking water as contamination of drinking water with c hlorfenapyr i s 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 Hu man Health Risk Assessment D416560

Page 6 of 56 

### 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 yield ed 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 equipm ent with a pin stream nozzle results in a combined MOE for children (1 to <2 years old) that is above the level o f concern ( LOC )

.

Aggregate Risk: Acute and chronic aggregate risk estimate s are based solely on dietary sources of exposure ; therefore, the exposure estimates provided in the dietary exposure analysis represent acute and chronic agg regate exposure and are not of concern. Short

- and intermediate

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

- application exposu re from the uses of chlorfenapyr in residential settings

. Since the short

- and intermediate

- term endpoint s 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 LO C (MOE = 60)

. Howe ver, 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 poten tial ” ; therefore, a quantitative cancer aggregate risk assessment was not performed.

Occupational Risk: For chlorfenapyr, based on the currently existing labeled use patterns, short

and intermediate

- term occupational exposures are expected. Most occup ational 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 handg un f or greenhouse applications, there are risks of concern (MOEs = 15

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

A n occupational post

- application assessment was conducted for workers entering greenhouses
after treatment of c rops 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 J

ustice: 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 Population s and Low

- Income Populations," http://epa.gov/compliance/ej/resources/policy/exec_order_12898. pdf.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 7 of 56 

### 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 requir ed 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 an alyzed 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 (F AR 

### ). This default value is 25% and is based on an analysis of 19 DFR studies where the F AR 

### valu e 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 F AR 

### value

seen was 47 % or approximately two times higher than the default residue trans fer 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 ≥ 2 00 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 MO Es are less than two times the LOC (i.e., < 2 00) 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 enf orcement 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 ChemistryChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 8 of 56 

### Laboratory for the subject livestock commodity chlorfenapyr methods (i.e. M 2405 for cattle liver, M 2398 for cat tle muscle

, and M2395.01 for cow milk).

2.2. 2 Tolerance Recommendations

Tolerances have been established in 40 CFR §1 80. 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, t he tolerance expression for chlorfenapyr should be updated to reflect current Agency policy as follows :

“Tolerances are established for resi dues 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

- (ethoxymethy l)

- 5

- (trifluoromethyl)

- 1 H

- 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 V egetable, 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 an d 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).

 F or mixers/loaders/applicators of liquids using a mechanically

- pressurized handg un for greenhouse applications , there are risks of concern (MOEs = 15

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

 Ba sed 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 risk s of concern with coarse

- stre am applications ofChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 9 of 56 

### 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 In troduction

Chlorfenapyr is a member of the pyrroles class of insecticide/miticides. It controls mites, caterpillar pests, thrips, and fungus gnats on fruiting ve getables 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. Th e 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 phosphor ylation 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

- 1 H

- pyrrole

- 3

- carbonitrile

CAS name 4

- bromo

- 2

- (4

- chlorophenyl)

- 1

- (ethoxymethyl)

- 5

- (trifluoromethyl)

- 1 H

- pyrrole

- 3

- carbonitrile
CAS registry number 122453

- 73

- 0
Registration Review Case No. 7419

Chemical Formula C 15 H 11 BrClF 3 N 2 O

Chemical structureChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 10 of 56 

### 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 pressuriz ed 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. T he pre

harvest 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.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 11 of 56 

### Table 3.3 .1. Existing Use Patterns/ Exposure Scenarios for Chlorfenapyr.

Registration Number and
Product Name Formulation a Application Equipment Maximum Application

R ates Max. No.

Applic ations Per
Season Use Directions and Limitations REI

Greenhouse ornamentals including Bedding Plants, Cut Flowers, Evergreens, Flowering plants, Foliage Plants, Fruiting Vegetabl es, 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
f ogger 0.011 lb ai/3000 ft 2

(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 ® SC b Backpack

Manually

pressurized
handwand

Mechanically

pressurized
hand gun 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 ( v egetable, fruiting, group 8

- 10 d )

241

- 374 Pylon ® SC b Backpack

Manually

pressurized
handwand

Mechanically

pressurized
hand gun 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 hoursChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 12 of 56 

### Table 3.3 .1. Existing Use Patterns/ Exposure Scenarios for Chlorfenapyr.

Registration Number and
Product Name Formulation a Application Equipment Maximum Application
R ates Max. No.

Applic ations 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 surf

aces.

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 applicab le 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

Mechanically

pressurized handwand/gun 0.5% dilution = 0.05 lb ai/gal

Limited exterior applications to doors, windows, eaves, attic
vents: 0.00023 lb ai/ft 2 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 applicableChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 13 of 56 

### Table 3.3 .1. Existing Use Patterns/ Exposure Scenarios for Chlorfenapyr.

Registration Number and
Product Name Formulation a Application Equipment Maximum Application
R ates Max. No.

Applic ations Per
Season Use Directions and Limitations REI

Nonagricultural outdoor buildings/structures

241

- 392
Phantom ® (Pre

- construction and Post

construction Termiticide Soil Treatments) EC

2 lb ai/gal Manual

- or

m echnically

pressurized handwand/gun

Inline injection
with lateral dispersal nozzle

Trenching and rodding 0.25% dilution = 0.0234 lb ai/gal

0.0936 lb ai/ft 2 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 p roduct listed for use on these sites in the Biological
and Economics Anal ysis Division’s ( BEAD’s ) Label Data Report. c. This includes commercial storages/warehouse premises, apartments, food storage areas, homes, hospitals, hotels, meat packi ng and food processing plants, motels, nursing homes, restaurants, and other food hand ling establishments, schools, hospitals/medical institutions, supermarkets, warehouses and other commercial and industrial bu ildings,
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 Hu man Health Risk Assessment D416560

Page 14 of 56 

### 3.4 Anticipated Exposure Pathways

The PRD has requested an a ssessment of human health risk to support Registration R eview 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 ap plication. 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 Environme ntal 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 Popu lations 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 we ll

- 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 assessm ents 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 perf ormed 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

- a pplication 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 subgro ups.

4.0 Hazard Characterization and Dose

- Response Assessment

Chlorfenapyr is an insecticide/miticide and a member of the class o f 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 sele ction, and FQPA SF evaluation. Since the scopingChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 15 of 56 

### 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 t he HED Hazard and Science Policy Council ( HASPOC) concluded using a weight

- of

evidence 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 an d 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 derm al absorption was found to be 13 % after 8 hours ( based on excreta, cage wash, blood, plasma, carcass, application site, and th e surrounding skin) and should be applied for converting oral doses to dermal equivalent doses to assess the potential risk associated with
der mal exposures of chlorfenapyr. The application site and surrounding skin were included since there is ongoing de pletion 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 overestimate d 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

- r elatedChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 16 of 56 

### 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 chan ges 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 of fspring 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 a t the HDT (44.0 and 48.3 mg/kg/day in males and females, respectively). Pa rental 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 th e 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 h ippocampus 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 n o 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 r obust 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 e xposure through lactation. Chlorfenapyr has a relatively high octanol

- water partition coefficient (logK OW 

### = 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 forChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 17 of 56 

### chlorfenapyr. The HIARC indicated that, according to EPA’s July 1999 Draft Guidelines fo r Carcinogen Risk Assessment , the current classifi cation category of “suggestive evidence of carcinogenicity, but not s ufficient to assess h uman carcinogenic p otential” was a better description of the intent of the 1996 Cancer Peer Review Committee.

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

T he RAB1 risk assessment team for chlorfenapyr determined that the FQPA SF should be
reduced t o 1X for all exposure scenarios. An acceptable DNT study has been submitted and now satisfies the pr evious 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
toxic i ty 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

a cross studies (see section 4.3 ), concern is low since the selected PODs are protective of
observed neurotoxic effects.

4.4.3 Evidence of Sensitivity/Susceptibili ty in the Developing or Young Animal

Although there is evidence of increased quantitative s usceptibility (see section 4.3 ), concern is
low since the offspring effects are well

- characterized with clearly established NOAEL /LOAEL
values and the endpoints sel ected for risk assessm ent 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 resi dential 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 D eparture Selections

Acute Dietary Endpoint (all populations): The acute reference dose (aRfD) for all populationsChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 18 of 56 

### 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. Expos ure 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 ac ute 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 neuroto xicity studies were
considered co

- critical for chronic dietary exposures. These studies are protective of all durations of exposure since there is n o progression of toxicity with time. The chronic reference dose (cRfD) was established using the NOAEL fro m 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 myeli n 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 In cidental 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 stud y is supportive of this endpoint with a similar NOAEL of approximately 5 mg/kg/day. This study was chosen because it is approp riate for th e 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 sc enarios 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 m ilk and fat. The

route

- specific dermal study was not chosen since the DNT prov ided 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 Hu man Health Risk Assessment D416560

Page 19 of 56 

### 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 reproducti on 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 fo r interspecies
extrapo lation, 10X for intraspecies variation , and 1X for FQPA SF when applicable ). No long

term exposures are expected based on the use pattern of chlorfenapyr . I nhalation 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 s ufficient to assess h uman carcinogenic p otential

. ” A qu antitative 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 Non

Occupational 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 UF A = 10X

UF H = 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

.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 20 of 56 Table 4.5. 3 .1. Summary of Toxicological Doses and Endpoints for Chlorfenapyr for Use in Dietary and Non

Occupational 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 UF A = 10X

UF H = 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
Intermediate

Term (1

- 6 months) NOAEL =

5 mg/kg/day UF A = 10X

UF H = 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 Short

Term (1

- 30 days) and
Intermediate

Term (1

- 6 months) NOAEL =

5 mg/kg/day

Dermal absorption
factor = 13 % UF A = 10X

UF H = 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
Intermediate

term (1

- 6 months) NOAEL =

5 mg/kg/day

Inhalation assumed equivalent to oral UF A = 10X

UF H = 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 “ s uggestive e vidence of c arcinogenicity, but n ot s ufficient to a ssess h uman

c arcinogenic p otential

. ” 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

- obs erved adverse

- effect level. LOAEL = lowest

- observed adverse

- effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population

- adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 21 of 56 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
Intermediate

Term (1

- 6 months) NOAEL =

5 mg/kg/day

Dermal absorption
factor = 13 % UF A = 10X

UF H = 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
Intermediate

term (1

- 6 months) NOAEL =

5 mg/kg/day

Inhalation assumed equivalent to oral UF A = 10X

UF H = 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 “ s uggestive e vidence of c arcinogenicity, but n ot s ufficient to a ssess h uman

c arcinogenic p otential

. ” 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

- ob served adverse

- effect level. LOAEL = lowest

- observed adverse

- effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivity among members of the human population (intraspecies). MOE = margin of exposure. LOC = level of concern.



### 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 toxici ty. 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 rat ios 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 dec i sion for chlorfenapyr, EPA revi ewed 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 Disr uptor 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 su bstance 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 ED SP where EPAChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 22 of 56 

### 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 betw een 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 pestic ide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 1 

### and 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 inc orporate 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

- dealky lation 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 assessmen ts 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 d rinking 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 upda ted 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)

- 1 H

- 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/

.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 23 of 56 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 Assessment 1

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: Greenh ouse 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 rat e 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, a nd 0.60

- 0.65 ppm in/on treated jalapeño peppers. Supporting data showed that re sidues generally declined with corresponding
increase s in the PHI.

Food Handling Establishments: BASF submitted data depicting the magnitude of chlorfenapyr
residues resul ting 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
col lected 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 n o existing or proposed uses of chlorfenapyr expected to r esult in contamination of drinking water

.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 24 of 56 

### 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 fo od 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 u nrefined and used tolerance

- level r esidues 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 typica lly considered to be processed; however, there is potential for imported tomatoes that have been treated with chlor f enapyr 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 tol erance

- level residues and 100% CT. As most tolerances for chlorfenapyr ar e 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 a pplications 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 chlor f enapyr to be processed. As a result, default processi ng 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 95 th 

### percentil e 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 aPA D at the 95 th 

### 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.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 25 of 56 

### 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 chlorfen apyr.

5.4.5 Summary Table

Table 5.4.5

. 1. Summary of Dietary (Food Only ) Exposure Risk for Chlorfenapyr a

.

Population Subgroup Acute Dietary (95 th 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 f our 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 ® 

### ] tha t have uses in residential settings. These uses are for general pest

control (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,

t here are currently no registered residential uses that permit resid ential handlers to use the products

– all labels indicate that products are “f or sale to, use and storage only by individuals/firms licensed or registered by the state to apply te rmiticide and/or general pest

control 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 environ ment 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) afterChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 26 of 56 

### 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 SOPs 3 

### . While not the only lifestage potent ially 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 i nterval 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).

I n 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

- applica tion inhalation exposure occurs while occupying living spaces within a residence after a pesticide treatment has occurred

. Post

- application inhalation exposure to chlorfenapyr

ca n result from the registered perime ter/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 assumptio n and factor is detailed in the 2012
Residential SOPs 3 

### and 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 expo sure and dose can be found i n Appendix C and/or the
2012 Residential SOPs 3



### .

All post

- application inhalation scenarios resulted in MOEs greater than the LOC for children and
adult s and, therefore, are not of concern. Table 6.2.1 .1 summarizes the post

- appl ication 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 M Label (mg) a Inhalation Dose

(mg/kg/day) b,c Short

- term Inhalation MOE d

Adult 11,350 0.000 1 50,000

Child 1 to < 2 years old 0.000 3 7 13, 000

a. Mass of active ingredient applied determined from product label (mg).
b. Inhalation Dose (mg/kg/day) = Exposure (mg/day) * Inhalation abso rption factor (unitless) / Body

- Weight (kg).

c. Exposure (mg/day) = IR*M Label * 1

- [((ACH * e

- k*ET )

– (K e - ACH

ET ))]
ACH * V

room ACH

- k
d . Inhalation MOE = NOAEL (5 mg/kg/da y) / Inhalation dose (mg/kg/day ).

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

- exposure

- sop.htmlChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 27 of 56 

### 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 purpose s 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

as sumption 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 de tailed in the 2012
Residential SOPs 3 

### and summarized in the most recent ORE memo (L. Venkateshwara; 8

- MAY

2014; D417598)

. The algorithms used to estimate residential post

- application dermal exposure and dose can be found in Appendix C and/or the 2012 Residential SOPs 3



### .

Table 6.2.2 .1 summarizes the dermal post

- application exposure and risk estimates from the

p erimeter/ sp ot/

b ed b ug 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 DepR a ( μ g/cm 2 ) Dermal Dose b (mg/kg/day) Dermal MOE c

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 0.00 68 740

Child 1 to < 2 years old 0.0056 890

Hard Surfaces Adult 0.0023 2, 2 00

Child 1 to < 2 years old 0.0037 1, 3 00

Crack and Crevice

Carpet Adult

0.3 0.0018 2,7 00

Child 1 to < 2 years old 0.0015 3, 3 00Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 28 of 56 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 DepR a ( μ g/cm 2 ) Dermal Dose b (mg/kg/day) Dermal MOE c

Hard Surfaces Adult 0.00061 8,1 00

Child 1 to < 2 years old 0.001 0 4

, 9 00

a. DepR = Deposited residue based on default assumptions in HED’s Residential SOPs.
b. Dose (mg/kg/day) = Deposited re sidue (μ g/cm 2 ) * Fraction transferred * Transfer coefficient (cm 2 /hr) * Exposure time (hr/day) * Conversion factor (0.001 mg/μ g) * Dermal Absorption Factor ( 13 %) / Body

- Weight ( 69 kg for adults and 11 kg for children 1 to < 2 years old).

c. MOE = P O D (mg/kg/day) / Dose (mg/kg/ day), where Short

- t erm dermal PO D = 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 ( μ g/cm

2 ) a Dermal Dose

(mg/kg/day) b Dermal MOE c

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/cm 2 ) * Surface area / Body

- weight Ratio (cm 2 /kg) * Fraction of body that contacts residue (0.5) * Conversion factor (0.001 mg/ μ g) * Fraction transferred (0.06) * Pro tection factor (0.5) * Dermal Absorption Factor (13 %).

c. MOE = PO D (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
activit ies can occur as a result of the indoor p erimeter/ sp ot/ b ed b ug application and the bed bug/mattress use. Only incidental oral exposures resulting from the in door 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

- to

mouth 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 p er imeter/spot/bed bug use. All hand

- to

- mouth post

- application exposure scenarios
resulted in MOEs higher than 1 00 and are t herefore not of concern.

Table 6.2. 3.2 summarizes the MOEs for object

- to

- mouth exposure of pesticide residues from the
indoor p erimeter/spot/bed bug use. All object

- to

- mouth post

- application exp osure scenarios
resulted in MOE s higher than 100 a nd are therefore not of concern.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 29 of 56 Table 6.2.3.1

. Post

- application Incidental Oral (Hand

- to

- Mouth) Exposure and Risk
Estimates for Childre n for Perimeter/Spot/Bed Bug Use of Chlorfenapyr.

Surface Type Dermal

Exposure a (mg/day) F aihands b SA H c (cm 2 ) HR d

(mg/cm 2 ) Oral Dose e

(mg/kg/day) Incidental Oral

MOE f

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 0.006 5 770

Hard Surface 0.0021 2,300

Crack and C revice

– Carpets

Carpet

0.3 0.15 150 0.0001 0.001 8 2,800

Hard Surface 0.0005 9 8,500

a. Dermal e xposure value from Table 6 .2.2.1

. b. Fraction of ai on hands.

c. Surface area of the hand (cm 2 ).
d. Hand r esidue l oading (mg/cm 2 ) = (F aihands * Dermal exposure) / (SA H * 2).

e. Oral Dose (mg/kg/day) = Exposure (mg/day)/ Body

- Weight (11 kg) ; where Exposure (mg/day) = HR * ( F M * SA H ) * (ET * N_Replen) * [1

- (1

- SE) (Freq_Replen / N_Replen) ].
f. MOE = PO D (mg/kg/day) / Daily Dose (mg/kg/day); incidental oral PO D = NOAEL = 5 mg/kg/day and LOC = 1 00

.

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 DepR a

(μ g/cm 2 ) F o b OR c Oral Dose d (mg/kg/day) Incidental Oral
MOE e

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 C revice

– 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. C hemical residue loading on the object (μ g/cm 2 ) = Deposited residue (μ g/cm 2 ) * Fo.
d. Oral Dose (mg/kg/day) = Exposure (mg/day)/ Body

- Weight (11 kg)

.
e. MOE = PO D (mg/kg/day) / Daily Dose (mg/kg/d ay); incidental oral PO D = NOAEL = 5 mg/kg/d ay and LOC = 100.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 30 of 56 

### 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 p erimeter/spot/bed bug and bed bug/mattress use. A s 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 c onsidered
inter

- related and it is likely that they occur interspersed amongst each other across time. Combining these scenarios with the dermal and inhalation exposure scenario s would be overly
conservative because of the conservative nature of each indiv idual 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 expo sure 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 t herefore 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, u se 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 MOE b Combined MOE c

Short

- and Intermediate

- term

Adult Dermal

– Perimeter/Spot/Bed Bug (coarse) 0.02 8 180

120 Inhalation

– Perimeter/Spot/Bed Bug 0.0001 50,000

Dermal

- bed bug/mattress 0.01 3 380

Adult Dermal

– Perimeter/Spot/Bed Bug ( pin

- stream ) 0.0068 740

250 Inhalation

– Perimeter/Spot/Bed Bug 0.00 0 1 50,000

Dermal

- bed bug/mattress 0.013 380

Child (1 to <2 years old) De rmal

- Perimeter/Spot/Bed Bug (c oarse) 0.023 220

6 2 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

1 2 0 Inhalation

– Perimeter/Spot/Bed Bug 0.00037 13

, 000

Hand

- to

- Mout h

– 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/MOE Dermal

– Perimeter/Spot/Bed Bug ) + (1/MOE Dermal

– bed bug mattress ) + (1/MOE Inhalation )]

Child (1 to <2 years old) Combined MOE = 1/ [(1/MOE Dermal

– Perimeter/Spot/Bed Bug ) + (1/MOE Dermal

– bed bug mattress ) + (1/MOE Inhalation ) + (1/MOE Hand

- to

- Mouth )]Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 31 of 56 

### 6.4 Residential Risk Estimates for Use in Aggregate Assess ment

Table 6.4. 1 reflects the residential risk estimates that are recommended for use in the aggregate
assessment for c hlorfenapyr

.

 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 MOE 2

Dermal 3 Inhalation Oral Total Dermal Inhalation Oral Total

Adult
Male /Female Post

application

exposure from indoor bed bug applications (coarse) 0.0 41 0.0001 N/A 0.041 120 50,000 N/A 120

Post

application

exposure from indoor bed bug applications (pin

- stream) 0.020 0.0001 N/A 0.020 250 50,000 N/A 250

Child Post

application

exposure from indoor bed bug applications (coarse) 0.0 5 3 0.00037 0.02 7 0.08 90 13,000 190 62

Post

application

exposure from indoor bed bug applications ( pin

- stream ) 0.0 356 0.00037 0.006 5 0.04 2 140 13,000 770 12 0

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

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

3 Dermal 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/te rmiticide for use on indoor andChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 32 of 56 

### 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 consid er 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 quantit ative
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 f or the following
scenarios: acute aggregate exposure , s hort

- and intermediate

- term aggregate exposure, and chronic aggregate exposure. Chlorfenapyr is classified as “ s uggestive e vidence of

c arcinogenicity, but n ot s ufficient to a ssess h uman c arcinogenic p otential” ; therefore

, a cancer aggregate ri sk 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 ar e not of concern to HED (<100% a PAD ) 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

neces sary since there is po tential for post

- application exposure from the uses of chlorfenapyr in residential settings . Since the short

- term assessment as sumed 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, t he 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 post

application dermal, inhalation, and incidental oral exposure from indoor applications (surfaces and mattresses) to control bed bugs . See Table 6. 4 .1 for more informatio n 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 MOE s 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

-Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 33 of 56 

### stream applic ations yields an aggregate MOE less than the LO C. However, u se 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) LOC 1 Max Exposure 2 (mg/kg/day) Average Dietary

Exposure (mg/kg/day) Residential

Exposure 3 (mg/kg/day) Aggregate MOE

(dietary and residential) 4

Adult (coarse) 5 100 0.05 0.001900 0.0 41 120

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 0.0 8 60

Children 1 to < 2 years old (pin

- stream) 5 100 0.05 0.004715 0.0 42 110

The bolded value is below the LOC of 100.

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

2 Maximum e xposur e (mg/kg/day) = NOAEL/LOC

. 3 Residential e xposure = 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 A ggregate Risk

There are no chronic residential exposure scenarios; therefore, the chronic aggregate risk is equival ent 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 mecha nism of toxicity finding as to chlorfenapyr and any other substances and chlorfenapyr does not appear to produce a toxic
metaboli te produced by other substances. For the purposes of this tolerance action, there fore, 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 ha ve 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 com mon 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 RiskChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 34 of 56 

### HED uses the term handlers to describe those individuals who are involved in the pesti cide 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 equ ipment 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

- pres surized 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

wa s not performed because dermal and inhalation exposure i s 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 wi thin 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 fog gers 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 l eft 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. A ppropriate safety directions and re

- entry restrictions should be included on the
label.

A series of assump tions 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

- cance r 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 Hu man Health Risk Assessment D416560

Page 35 of 56 

###  Fo r 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 wi th 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 respi rator.

 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 clothin g, 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 respira tor.

 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 Hu man Health Risk Assessment D416560

Page 36 of 56 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
Rate 2 Area

Treated or
Amount
Handled Daily 3 Dermal Inhalation Total

Mitigation Level (Baseline unless specified) Mitigation Level

(Baseline unless specified) Dose 4 (mg/kg/day) MOE 5 Dose 6 (mg/kg/day) MOE 7 MOE 8

Mixer/Loader/Applicator
Injector (termiticide) Structural (termiticide) 1,300 2 0.0234 lb ai/gal 124 gal 9 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

Manually

Pressurized
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

Mechanically

Pressurized 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 r egistered 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/l b 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/In halation 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 Hu man Health Risk Assessment D416560

Page 37 of 56 

### 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 re

entry exposure). Such exposures may occ ur 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 ac tivity, 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 fo r 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 pr imarily 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 ex posure 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,
2010 4



### . The Agency is in the process of evaluating the SAP report as well as avail able post

application 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

- applicatio n 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

- applica tion 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.htmlChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 38 of 56 

### ORE memo (L. Venkateshwara; 8

- MAY

- 2014; D417598)

. The algorithms used to estimate non

cancer 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 1 20 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 (cm 2 /hr) DFR/TTR 1 Dermal Dose (mg/kg/day) 2 MOE 3

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 0.01 6 310

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, Non

bearing 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/cm 2 ; where F = 0.25 and D = 0.10 per day

2 Daily Dermal Dose = [DFR (μg/cm 2 ) × 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/cm 2 ) × TC × 0.001 mg/μg × 8 hrs/day × dermal absorption factor ( 13 %)]  BW 69 kg).



### Re stricted 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), a ctive ingredients classified as Acute III or IV for acute dermal, eye irritation

, and prim ary 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 chlorfenap yr.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 39 of 56 

### 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:RAB1Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 40 of 56 

### A ppendix 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 yes 1

yes
yes 1

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

yes 2

yes 870.7485 Metabolism and Pharmacokinetics

................................ 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity

................................ ............................. yes

no

no 3 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).Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 41 of 56 

### A.2 Toxicity Profile s

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 co rd of male

rats, and increased liver weight in males and females, increased absolute liver weight in females
and decreas ed 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 Non

Rodent (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

.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 42 of 56 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 increase s (absolute and relative) in
both sexes.

870.3465 90

- Day Inhalation

Study (rat) 46654701 (2005)

Acceptable/guideline 0, 5, 20, 40, 80 mg/m 3 NOAEL = 20 mg/m 3

. LOAEL = 40 mg/m 3 based on visually accelerated respiration, increased white blood cell and lymphocyte counts, and changes in cl inical parameters in both sexes.

Mortality observed in males at 80 mg/m 3

. 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 high

dose in the F 2 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) base d on decreased body

- weight.

870.4200a Carcinogenicity (rat) See 870.4300 See 870.4300Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 43 of 56 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/da y (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 base d 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 adenom as/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 t est 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 ass a y 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

conce ntration range of 3.5

- 14.1 μg/mL +S9. High er 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

.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 44 of 56 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 C NS 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 mo tor 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

r adioactivity 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 chlo rfenapyr 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/cm 2 and 0.0217 mg/cm 2 At 8, 24, and 120 hours, dermal absorption (tissues, excreta, surrounding skin, and application site) for the 2.4 mg/cm 2 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/cm 2 dose was 13.1%, 10.7 %, and
15.1 %, respectively.Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 45 of 56 

### 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 K ow = 67,670 (log K
ow = 4.83) at 25  C

pH 7.16; 1% aqueous slurry at 24  CChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 46 of 56 

### 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 do se 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 u sing 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 oc cupational 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:

DFR t 

### =AR * F* (1

- D) t 

### * ( 4 .54E8 ug
lb ) * ( 2.47E

- 8 A

cm 2 

### )Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 47 of 56 

### where:

DFR t 

### = dislodgeable foliage residue on day "t" (μg/cm 2 

### ),
AR = a pplication r ate (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 = e xposure (mg ai/day),
TC = t ransfer coefficient (cm 2 

### /hr),

DFR t 

### = d islodgeable f oliar r esidue on day “t” (μg/cm 2 

### ), and

ET = e xposure t ime (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 = e xposure (mg ai/day),
AF = absorption fa ctor (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 t o the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational post

- application workers

. All MOE values a re calculated using the following formula:

MOE= POD

ADD

where:
MOE = margin of exposure: value used by HED to represent risk estimates (unitl ess),
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 vaporsChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 48 of 56 

### The following algorithm is used to determine post

- application inhalation exposure from indoor
surface

- directed sprays:

E = IR ∗ M label 

### ACH ∗ V

room 

### [ 1

− ( ( ACH ∗ e − k ∗ ET 

### )

− ( k ∗ e − ACH ∗ ET



### ACH

− k ) ]

where : E = exposure (mg/day);

IR = inhalation rate (m 3 

### /hr);

M label 

### = mass of active ingredient applied, determined from product label (mg);

V room 

### = volume of room (m 3 

### );
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 act ive ingredient applied can be calculated using the following formula:

M label 

### = AR ∗ A ∗ CF 1

where:

M label 

### = mass of active ingredient applied, determined from product label (mg);
AR = application rate (e.g., lb ai/ft 2 

### , lb ai/gal);
A = area treated or amount handled (e.g., ft 2 

### /day, gal/day); and
CF1 = conversion factor (4.54x10 5 

### 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 calcu lating such a decay rate based on work done by Chinn (1981). Chinn developed the following relationship between the volatility, or saturation concentration (C sat 

### ), of a chemical and the time required for 90% of the chemical to evaporate (EvapT):

Ev a pT = 10 [ 7

. 3698

− 0

. 9546 ∗ log 10 ( C sat ) ]



### where : EvapT = evaporation time (sec); and
C sat 

### = saturation concentration (mg/m 3 

### ).

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 ) ∗ CF 1
EvapTChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 49 of 56 

### 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 pestic ide applied, not the concentration of the pesticide in the air; therefore, the reviewer must check that the input for mass applied (M label 

### ) is predicting an air concentration less than or equal to the saturation concentration. The following equation can b e used to calculate the theoretical mass applied that would result in an air concentration that reaches the saturation concentration for a pesticide (M Csat 

### ):

M C sat 

### = C

sat 

### ∗ ( ACH

− k ) ∗ V

k

M Csat 

### should be compared to M label



### .

 If M label 

### > M Csat 

###  M label 

### will predict an air concentration higher than the saturation
concentration. Use M Csat 

### in the exposure calculation.

 If M label 

### < M Csat 

### ,  M label 

### will not predict an air concentration higher than the saturation
concentration. Use M label 

### 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 (inhal ation); 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

(m 3 /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

V room Volume of room

(m 3 ) 33

Variables Specific to Post

- application Inhalation Exposure to Pesticide VaporsChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 50 of 56 Table C.1. Indoor Environments

– Inputs for Residential Post

- application Inhalation Exposure

. Algorithm
Notation Exposure Factor

(units) Point Estimate(s)

C sat Saturation concentration

(mg/m 3 ) 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

M label 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 ∗ CF 1

where : E = exposure (mg/day);

TR = indoor surface transferable residue (μg/cm 2 

### );
TC = transfer coefficient (cm 2 

### /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 ∗ F ai



### where : TR = indoor surface transferable residue (μg/cm 2 

### ); DepR = deposited residue (  g/cm 2 

### ), based on (in order of preference):

(1) Chemical

- specific residue deposition data (  g/cm 2 

### ), (2) Application rate (lb ai/area), or (3) Default residue bas ed on type of application (  g/cm 2 

### ); and

F ai 

### = 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

BWChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 51 of 56 

### 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/cm 2 ) - Estimated: DepR * F ai

DepR Deposited residue

(  g/cm 2 ) - Estimated based on default residue related to type of application

F ai Fraction of DepR as TR

following application Carpets 0.06 a

Hard surfaces 0.08 a

TC Transfer Coefficient

(cm 2 /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 ∗ F

ai 

### ∗ PF ∗ AF ∗ CF 1

where:

D = Dermal dose (mg/kg

- day);

DR = Deposited residue (mg/cm 2 

### );
SA/BW = Surface area / Body

- Weight Ratio (cm 2 

### /kg);

F = Fraction of body that contacts residue;

CF1 = Conversion factor (mg/  g);
AF = Absorption factor;

F ai 

### = 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/cm 2 ) B ased on default residue valuesChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 52 of 56 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 (cm 2 /kg) Adult 280

Children 1 < 2 years old 640

F Fraction of body that contacts residue 0.5

F ai 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 ∗ ( F

M 

### ∗ SA H 

### ) ∗ ( ET ∗ N

_ Replen ) ∗ ( 1

− ( 1

− SE ) Freq

_ HtM
N

_ Replen 

### ) ]

where:

E = exposure (mg/day);

HR = hand residue loading (mg/cm 2 

### );

F M 

### = fraction hand surface area mouthed / event (fraction/event);

ET = exposure time (hr/day);
SA H 

### = surface area of one hand (cm 2 

### ); 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).

a nd

HR = Fai h ands 

### ∗ DE

SA H 

### ∗ 2

where : HR = hand residue loading (mg/cm 2 

### );
Fai hands 

### = fraction ai on hands compared to total surface residue from jazzercise study (unitless);

DE = dermal exposure (mg); and
SA H 

### = typical surface area of one hand (cm 2 

### ).

and

Dose, normalized to body

- weight, is calculated as:Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 53 of 56 

### 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)

Fai hands 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/cm 2 ) Calculated

SA H Surface area of one hand (cm 2 ) Children 1 < 2 years old 150

AR Application rate

(mass active ingredient per unit area) 11,350

F M 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 ∗ CF 1 ∗ SAM O 

### ∗ ( ET ∗ N

_ Replen ) ∗ ( 1

− ( 1

− SE ) Freq

_ OtM
N

_ Replen 

### )

where:

E = exposure (mg/day);

OR = chemical residue loading on an object (  g/cm 2 

### );

CF1 = weight unit conversion factor (0.001 mg/  g);
SAM O 

### = area of the object surface that is mouthed (cm 2 

### /event);Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 54 of 56 

### 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 ∗ F O



### where : OR = chemical residue loading on the object (μg/cm 2 

### ); DepR = deposited residue (μg/cm 2 

### ); and

F O 

### = fraction of residue transferred to an objec t (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

F O Fraction of residue

transferred to an object Carpets 0.06 a

Hard surfaces 0.08 a

SAM O Surface area of object mouthed

(cm 2 /event) 10

N_Replen Replenishment intervals per hour

(intervals/hour) 4

SE O 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 11Chlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 55 of 56 

### Appendix D. Registered C hlorfenapyr End

- Use Products

Table D.1. Registered C h lorfenapyr 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 CorporationChlorfenapyr Preliminary Hu man Health Risk Assessment D416560

Page 56 of 56 

### 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 f rom 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 website 5



### .

5 http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/pestici des/science/post

- app

- exposure

- data.html