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Chlorfenapyr Proposed Interim Decision - Table of Contents

Contents

I. INTRODUCTION............................................................................ 4

A. Public Comments..............................................................................6

II. USE AND USAGE...........................................................................6

III. SCIENTIFIC ASSESSMENTS........................................................................... 6

A. Human Health..................................................................................6

1. Risk Conclusions......................................................................7

Dietary Assessment.........................................................................7

Residential Assessment.....................................................................7

Aggregate Assessment.....................................................................8

Cumulative Assessment....................................................................8

Occupational Assessment.................................................................. 8

2. Human Incidents.....................................................................9

3. Tolerances.............................................................................9

B. Ecological....................................................................................... 10

1. Risk Conclusions..................................................................... 10

2. Pollinator Studies and Assessments................................................11

C. Endangered Species Assessment............................................................12

D. Endocrine Disruptor Screening Program...................................................12

IV. PROPOSED INTERIM REGISTRATION REVIEW DECISION..................... 13

A. Risk Mitigation and Regulatory Rationale.................................................13

B. Tolerance Amendments.......................................................................17

C. Proposed Interim Registration Review Decision..........................................17

V. NEXT STEPS AND TIMELINE............................................................18

A. Interim Registration Review Decision.....................................................18

B. Implementation of Mitigation Measures...................................................18
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References:

This Preliminary Interim Decision summarizes the Environmental Protection Agency's current 

position based on the following documents:

1. Registration Review: Preliminary Ecological Risk Assessment and Endangered Species 

Effects Determination for Chlorfenapyr. Stephen P. Wente. June 12, 2014.

2. Chlorfenapyr- Preliminary Human Health Risk Assessment for Registration Review. 

Monique M. Perron, William D. Wassell, and Lata Venkateshwara. May 22, 2014.

3. Chlorfenapyr. Revised Occupational and Residential Exposure Registration Review 

Assessment. Lata Venkateshwara. June, 18 2014.

4. Chlorfenapyr. Addendum to Registration Review Preliminary Risk Assessment to Update 

Occupational Post-application Assessment based on Submitted Dislodgeable Foliar Residue 

(DFR) Data. Kelly M. Lowe. March 10, 2015.

5. Chlorfenapyr: Review of Human Incidents. Khin Oo and Shanna Recore. February 25, 

2010.

These and other supporting documents for the chlorfenapyr registration review case may be 

found in the docket EPA-HQ-OPP-2010-0467 at http://www.regulations.gov.
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I. INTRODUCTION

This document is the Environmental Protection Agency’s (EPA or the Agency) Proposed Interim 

Registration Review Decision (PID) for chlorfenapyr (case 7419, PC 129093) and is being issued 

pursuant to 40 CFR sections 155.56 and 155.58. A registration review decision is the Agency's 

determination whether a pesticide meets, or does not meet, the standard for registration in the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The Agency may issue, when it 

determines it to be appropriate, an Interim Registration Review Decision before completing a 

registration review. Among other things, the Interim Registration Review Decision may: 1)

require new risk mitigation measures; 2) impose interim risk mitigation measures; 3) identify 

data or information required to complete the review; and 4) include schedules for submitting the 

required data, conducting the new risk assessment and completing the registration review. For 

further information on chlorfenapyr, additional documents can be found in EPA’s public docket 

(EPA-HQ-OPP-2010-0467) at www.regulations.gov.

FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the 

continuous review of existing pesticides. All pesticides distributed or sold in the United States 

generally must be registered by the EPA based on scientific data showing that they will not cause 

unreasonable risks to human health or to the environment when used as directed on product 

labeling. The registration review program is intended to make sure that, as the ability to assess 

and reduce risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects. Changes in science, public 

policy, and pesticide use practices will occur over time. Through the registration review 

program, the Agency periodically re-evaluates pesticides to make sure that as these changes 

occur, products in the marketplace can continue to be used safely. Information on this program is 

provided as www.epa.gov/oppsrrd1/registration_review/.

In 2006, the Agency implemented the registration review program pursuant to FIFRA section 

3(g) and will review each registered pesticide every 15 years to determine whether it continues to 

meet the FIFRA standard for registration.

Chlorfenapyr is a member of the pyrroles class of insecticide/miticides. It acts by disrupting 

adenosine triphosphate (ATP) production, leading to cell dysfunction in the target organism. 

Chlorfenapyr is registered for application to fruiting vegetables and ornamentals in greenhouses 

only and crack/crevice/spot treatment on indoor and outdoor residential sites (including as a bed 

bug treatment), food/feed handling areas, indoor and outdoor commercial sites (including 

sewers), and indoor medical sites. It is not registered for use on outdoor agricultural crops.

Chlorfenapyr is used to controls mites, caterpillar pests, thrips, fungus gnats, cockroaches, ants, 

and termites. Since chlorfenapyr was first registered in 2001, it was not subject to reregistration.

Pursuant to 40 CFR section 155.50, EPA formally initiated registration review for chlorfenapyr

(case 7419). The following summary highlights significant events that have occurred during the 

registration review of chlorfenapyr and can be found in EPA’s public docket, EPA-HQ-OPP2010-0467, accessed at www.regulations.gov:

• June 23, 2010– Publication of chlorfenapyr preliminary work plan (PWP), entitled 

Chlorfenapyr Summary Document Registration Review: Initial Docket June 2010, for a 
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60-day public comment period. The PWP was accompanied by the scoping document and 

problem formulation.

• January 6, 2011 – A final work plan (FWP) for chlorfenapyr, entitled Chlorfenapyr Final 

Work Plan (FWP) for Registration Review: November 2010, was issued. Three public 

comments were received during the 60-day comment period for the chlorfenapyr PWP. 

Comments and label changes submitted by the chlorfenapyr technical registrant resulted 

in a change of the data needs identified in the PWP.

o EPA’s consideration of public comments on the chlorfenapyr FWP are detailed in 

the following two response to comments documents:

 Chlorfenapyr. Public Comments Regarding the Health Effects Division's 

(HED's) Human-Health Assessment Scoping Document in Support of 

Registration Review of 26-MAY-2010. HED's Response to Public 

Comments. Anwar Y Dunbar. November 4, 2010.

 Response to Comments on the Preliminary Problem Formulation for 

Chlorfenapyr. Robert A. Miller and Steve Wente October 28, 2010.

o The FWP modified the PWP in concluding that there is no significant outdoor 

environmental exposure from the use of chlorfenapyr, and that EPA would 

therefore not conduct a comprehensive ecological risk assessment during 

registration review.

 Compost Concerns Resolved: Certain chlorfenapyr product labeling 

previously allowed chlorfenapyr-treated plant material to be composted,

raising concerns about possible environmental exposure from treated plant 

matter. After the chlorfenapyr PWP was issued, the label language 

allowing composting was removed and the following prohibition was 

added: “DO NOT compost any discarded plant materials that have been 

treated with this product.”

 Termiticide Use: EPA initially identified potential environmental exposure 

from the use of chlorfenapyr in construction as a termiticide applied to the 

soil underlying a concrete slab prior to the slab being poured. However, at 

this time EPA does not believe this exposure route is sufficient to warrant 

the collection of additional fate and effects data or the development of an 

ecological risk assessment.

• October 12, 2011 – Generic Data Call-In (GDCI-129093-1034) for chlorfenapyr was

issued.

• July 1, 2014– The Agency published the Registration Review: Preliminary Ecological 

Risk Assessment and Endangered Species Effects Determination for Chlorfenapyr and the 

Chlorfenapyr- Preliminary Human Health Risk Assessment for Registration Review for a 

60-day public comment period. Two comments were received during the comment 

period, and a discussion of these comments follows in section I.A. of this PID.

• July 2015 – The Agency is now publishing the Chlorfenapyr Proposed Interim 

Registration Review Decision, in docket number EPA-HQ-OPP-2010-0467 for a 60-day 
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public comment period. In addition to this document, the Agency is also publishing the 

following supporting documents:

o Chlorfenapyr. Addendum to Registration Review Preliminary Risk Assessment to 

Update Occupational Post-application Assessment based on Submitted 

Dislodgeable Foliar Residue (DFR) Data. Kelly M. Lowe. March 10, 2015.

A. Public Comments

Two comments were received during the comment period for the chlorfenapyr preliminary 

ecological risk assessment and draft human health risk assessment. To address these two 

comments on the preliminary ecological risk assessment, EPA drafted an October 28, 2014 

memo entitled Response to Public Comments on the Registration Review: Preliminary 

Ecological Risk Assessment and Endangered Species Effects-Determination for Chlorfenapyr. 

This document was posted to the chlorfenapyr docket on November 7, 2014. One comment 

(EPA-HQ-OPP-2010-0467-0022) was an anonymous public comment disputing the Agency’s 

finding of no ecological risks of concern for chlorfenapyr due to an incomplete exposure 

pathway. The second was a comment (EPA-HQ-OPP-2010-0467-0023) from the Center for 

Biological Diversity supporting EPA’s No Effect finding for chlorfenapyr under the Endangered 

Species Act (ESA). EPA thanks the Center for Biological Diversity for their comment and 

reiterates the Agency’s finding of a “No Effect” (NE) determination for all listed species as well 

as a No Habitat Modification determination for all designated critical habitats for the currently 

registered uses of chlorfenapyr. 

II. USE AND USAGE

Chlorfenapyr is a member of the pyrroles class of insecticide/miticides, which works by 

disrupting ATP production in the target pests, leading to cell dysfunction. Chlorfenapyr is 

registered for application to fruiting vegetables and ornamentals in greenhouses only and 

crack/crevice/spot treatment on indoor and outdoor residential sites (including as a bed bug 

treatment), food/feed handling areas, indoor and outdoor commercial sites, and indoor medical 

sites. It is not registered for use on outdoor agricultural crops. Outdoor uses are limited to 

crack/crevice/spot treatments and use as a termiticide applied to soil prior to the pouring of 

concrete slabs in construction.

III. SCIENTIFIC ASSESSMENTS

A. Human Health 

A summary of the Agency’s human health risk assessment is presented below. The Agency used 

the most recent Agency science policies and risk assessment methodologies to prepare a 

quantitative risk assessment in support of the registration review of chlorfenapyr. For a detailed 

discussion of the human health assessment for chlorfenapyr, see Chlorfenapyr- Preliminary 

Human Health Risk Assessment for Registration Review dated May 22, 2014 and Chlorfenapyr. 
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Addendum to Registration Review Preliminary Risk Assessment to Update Occupational Postapplication Assessment based on Submitted Dislodgeable Foliar Residue (DFR) Data dated 

March 10, 2015. Both documents are available in the public docket EPA-HQ-OPP-2010-0467, 

which can be accessed at http://www.regulations.gov/.

1. Risk Conclusions

Dietary Assessment:

There are no dietary risk estimates of concern for chlorfenapyr from either acute or chronic 

exposure. In addition, there are no existing or proposed uses of chlorfenapyr expected to result 

in contamination of drinking water. Acute and chronic dietary analyses were conducted using

tolerance-level residues and 100% crop treated (CT).

Dietary risk incorporates both exposure to and toxicity of a given pesticide, and is expressed as a 

percentage of a level of concern. The level of concern is the dose predicted to result in no 

unreasonable adverse health effects to any human population subgroup, including sensitive 

members of such population subgroups. This level of concern is referred to as the population 

adjusted dose (PAD), which reflects the reference dose (RfD), either acute or chronic, adjusted to 

account for the FQPA safety factor.

The acute dietary exposure for chlorfenapyr 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 for chlorfenapyr 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. 

Estimated risks that are less than 100% of the PAD are below EPA’s level of concern.

Residential Assessment:

Because there are no registered or proposed residential handler uses of chlorfenapyr, a residential 

handler exposure assessment was not conducted. Although certain chlorfenapyr products are 

approved for use in residential settings, these products are intended for use by homeowners 

themselves. This distinction is made on chlorfenapyr product labelling. All four chlorfenapyr 

registrations currently approved for use in household/domestic dwellings feature label language 

stating that the product is “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.”

There is, however, potential for residential post-application exposure from chlorfenapyr. The 

residential post-application exposure assessment calculated that there was one residential 

chlorfenapyr exposure scenario with risks of concern: combined risk from post-application 

incidental oral, dermal, and inhalation exposure for children (1 to <2 years old) with coarsestream applications for indoor bed bug treatment. This scenario resulted in a potential risk of 

concern with a margin of exposure (MOE) of 62, based on the assumption of a dermal absorption 

factor (DAF) of 13%. For chlorfenapyr, EPA’s Level of Concern (LOC) is ≥ 100. This means 

that EPA considers MOE values lower than 100 to be a potential risk of concern for 

chlorfenapyr. MOEs at or above the LOC are not of concern.
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Aggregate Assessment:

Non-Cancer Risks: Short- and intermediate-term aggregate risks for chlorfenapyr are based on a 

combination of dietary and residential assessment data, while acute and chronic aggregate risk 

estimates for chlorfenapyr are based solely on dietary sources of exposure. Because there are no 

dietary risk estimates of concern for chlorfenapyr, there are no acute and chronic aggregate 

exposures of concern.

There was, however, one scenario of potential concern for short- and intermediate-term exposure 

to chlorfenapyr. Short and intermediate-term aggregate risk assessments were performed 

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

residential settings. Since the short- and intermediate-term endpoints and points of departure 

(PODs) are the same, the short-term aggregate assessment is protective of intermediate-term 

exposure. EPA found that the short-term aggregate MOE for adults is greater than EPA’s LOC 

(MOEs ≥ 100), and is therefore not a risk of concern. The same safety finding was not made for 

risks to young children exposed to chlorfenapyr. For children (1 to <2 years old), the short-term 

aggregate exposure with coarse-stream applications yields an aggregate MOE of 60. This value 

of 60 is less than the LOC of 100 and therefore a risk of potential concern.

Cancer Risks: Chlorfenapyr is classified as “suggestive evidence of carcinogenicity, but not 

sufficient to assess human carcinogenic potential.” Therefore, a quantitative cancer aggregate 

risk assessment was not performed.

Cumulative Assessment:

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

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

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

metabolite produced by other substances, so a cumulative risk assessment has not been 

conducted.

Occupational Assessment:

For chlorfenapyr, based on the currently existing labeled use patterns, short and intermediateterm occupational exposures are expected. An occupational assessment for chlorfenapyr was part 

of the Chlorfenapyr - Preliminary Human Health Risk Assessment for Registration Review, dated 

May 22, 2014. Both handler and post-application assessments were conducted.

• Handler Risk: Most occupational handler risk estimates resulted in MOEs greater than the 

LOC at baseline or label specified levels of personal protective equipment (PPE), and 

therefore, are not of concern1

. However, several exposure scenarios required additional 

 1 Note on Termiticide – Crack and Crevice Treatment: For this use scenario, there was an oversight in table 9.1.1 of 

the 2014 human health risk assessment. It was not noted that the values presented were for single layer with gloves 

rather than for a baseline level of PPE. For applicators using ready-to-use aerosol cans for application as a 

termiticide crack and crevice treatment, combined MOEs were below the LOC of 100 at baseline levels of PPE 

(MOE of 56). Current PPE, which includes a single layer of clothing (i.e. a long-sleeved shirt, long pants, and shoes 

plus socks, but no gloves or respirator), yields this total MOE value of 56. If gloves are added, a total MOE of 130 

will be reached and the use scenario will no longer be of concern.
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PPE to reach total MOEs greater than the LOC. For the use scenario of 

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

greenhouse applications, there are risks of concern (MOE = 26) even with maximum PPE 

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

• Post-Application Risk: An occupational post-application assessment was conducted for 

workers entering greenhouses after treatment of crops and/or ornamentals. Using a 

default Dislodgeable Foliar Residue (DFR) value of 0.56, risk estimates for all postapplication scenarios were not of concern. 

Since the default DFR value yielded dermal MOEs less than two times the LOC (i.e., < 200) 

based on default values for the fraction of application rate available for transfer after a foliar 

application, the 2014 human health risk assessment for chlorfenapyr called for the submission of 

a DFR study. The chlorfenapyr registrant provided a DFR study, which was reviewed and found 

acceptable for use in registration review by the Agency. On the basis of this new DFR data, EPA 

revised its occupational post-application assessment for chlorfenapyr in the March 10, 2015 

memo Chlorfenapyr. Addendum to Registration Review Preliminary Risk Assessment to Update 

Occupational Post-application Assessment based on Submitted Dislodgeable Foliar Residue 

(DFR) Data. Updated short- and intermediate-term occupational post-application exposure 

scenarios were calculated for currently registered uses of chlorfenapyr:

• Post-Application Risk: All use scenarios resulted in MOEs greater than the LOC of 100 

(ranging from 880 to 28,000) on day 0 (12 hours after application) and are therefore not 

of concern to EPA. MOEs for all occupational post-application non-cancer exposure 

scenarios increased from those calculated in the 2014 human health risk assessment, 

indicating that risks were even lower than previously believed. 

• Handler Risk: Occupation handler risk was not discussed in the 2015 memo. The 

Agency’s characterization for this risk category remains unchanged from the 2014 

chlorfenapyr assessment.

2. Human Incidents

Human incidents involving chlorfenapyr are described in the February 25, 2010 memo 

Chlorfenapyr: Review of Human Incidents. An analysis of the OPP Incident Data System (IDS) 

database from 2002 to 2010 found two incidents, and an analysis of the Centers for Disease

Control and Prevention/National Institute for Occupational Safety and Health (CDC/NIOSH)

Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) database found 

six incidents from the time range of 1998-2006. Based on the low severity and low number of 

incident cases, there does not appear to be a concern at this time that would warrant further 

investigation. The Agency will continue to monitor the incident information and if a concern is 

triggered, additional analysis will be included in a future risk assessment.

3. Tolerances

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. Due to 

 
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updates in crop grouping, existing tolerances for vegetable, fruiting group 8 (1.0 ppm) needs to 

be revised to vegetable, fruiting, group 8-10.

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

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

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

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

an issue.

B. Ecological

A summary of the Agency’s ecological risk assessment is presented below. The Agency used 

the most updated Agency science policies and risk assessment methodologies to prepare a 

qualitative risk assessment in support of the registration review of chlorfenapyr. For a detailed 

discussion of the ecological assessment for chlorfenapyr, see Registration Review: Preliminary 

Ecological Risk Assessment and Endangered Species Effects Determination for Chlorfenapyr, 

dated June 12, 2014, available in the public docket EPA-HQ-OPP-2010-0467, which can be

accessed at http://www.regulations.gov/. 

The Agency also completed an endangered species assessment for chlorfenapyr. Based on 

incomplete exposure pathways for all chlorfenapyr uses, the Agency made a No Effects (NE) 

determination for all listed species as well as a No Habitat Modification determination for all 

designated critical habitats for the currently registered uses of chlorfenapyr.

1. Risk Conclusions

As described in the Introduction (Section 1) of this Proposed Interim Decision, potential 

concerns regarding environmental exposure from (1) chlorfenapyr’s termiticide use in 

construction settings and (2) from the formerly permitted composting of chlorfenapyr-treated 

plant materials were addressed in the 2011 chlorfenapyr Final Work Plan. Aside from 

chlorfenapyr’s termiticide use, all other chlorfenapyr use sites are indoors and result in no 

complete environmental exposure pathways, or are crack and crevice treatments with little 

potential for outdoor release. EPA therefore concluded that there were incomplete 

environmental exposure pathways for all chlorfenapyr uses.

As noted in EPA’s 2014 memo Response to Public Comments on the Registration Review: 

Preliminary Ecological Risk Assessment and Endangered Species Effects-Determination for 

Chlorfenapyr, the Agency’s use of the phrase “incomplete exposure pathway” should not be 

mistaken for the idea of no (zero) exposure. The Agency uses the phrase “incomplete exposure 

pathway” to indicate that any potential exposure to an ecological receptor (non-target organism) 

through registered (legal) uses of a pesticide would be far below the level necessary to cause 

harm to that receptor. Based on incomplete exposure pathways for all chlorfenapyr uses, the 

Agency made a No Effects (NE) determination for all listed species as well as a No Habitat 
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Modification determination for all designated critical habitats for the currently registered uses of 

chlorfenapyr. In addition, risks of concern are unexpected for non-listed species. 

Because no complete exposure pathway was identified for chlorfenapyr, ecological risks from 

chlorfenapyr were not assessed quantitatively in the chlorfenapyr preliminary ecological risk 

assessment. If in the future chlorfenapyr is considered for additional uses that could result in 

environmental releases, further analysis will need to be undertaken to determine potential effects 

to non-target organisms, including listed species and their designated critical habitat.

2. Pollinator Studies and Assessment

When initially scoping the registration review for chlorfenapyr, EPA did not identify the need for 

any additional studies to evaluate potential effects on pollinators. However, since the issuance of 

the June 2014 Guidance for Assessing Pesticide Risks to Bees[1], EPA has begun to require these 

data where applicable. EPA is currently determining whether additional pollinator data are 

needed for active ingredients in registration review whose dockets opened prior to June 2014. 

For those active ingredients where EPA determines that additional pollinator exposure and 

effects data are necessary to help make a final registration review decision, EPA intends to issue 

a DCI to obtain these data. In the near future, EPA will provide further information and 

guidance on this effort. The pollinator studies that could be required are included in Table 1 

below. The Agency will require data it believes are needed to help inform the pollinator risk 

assessment.

Table 1. Potential Pollinator Data Requirements

Guideline # Study

850.3020* Acute contact toxicity study with adult honey bees

850.3030* Honey bee toxicity of residues on foliage

850.3040** Field testing for pollinators

Non-Guideline* 

(OECD 213)

Honey bee adult acute oral toxicity

Non-Guideline* 

(OECD 237)

Honey bee larvae acute oral toxicity

Non-Guideline* Honey bee adult chronic oral toxicity

Non-Guideline* Honey bee larvae chronic oral toxicity

NonGuideline** Residues in pollen and nectar/field residue analysis

NonGuideline** 

(OECD 75)

Semi-field testing for pollinators (tunnel or colony feeding 

studies)

*Tier 1 (Laboratory-based studies)

**Tier 2 and 3 (Semi-field and full field colony-level studies) The need for a higher tier test for pollinators will be determined 

based upon lower-tiered tests and/or other lines of data and the need for a refined pollinator risk assessment.

 [1] http://www2.epa.gov/sites/production/files/2014-

06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf
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C. Endangered Species Assessment

There is no reasonable expectation for registered uses of chlorfenapyr to cause direct or indirect 

adverse effects to threatened and endangered species. No adverse modification of critical habitat 

is expected from the use of chlorfenapyr. EPA has made a “no effect” determination under the 

Endangered Species Act (ESA) for all listed species as well as a “no habitat modification” 

determination for all designated critical habitats for the currently registered uses of chlorfenapyr. 

The Agency has therefore concluded that consultation with the Fish and Wildlife Service and the 

National Marine Fisheries Service under ESA section 7(a)(2) is not required. EPA anticipates 

conducting no further analysis of potential risks to endangered or threatened species, unless data 

or information are obtained during the Registration Review process that would indicate such an 

assessment would be needed to inform the Agency’s decision.

D. Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

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

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

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

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

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

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

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

taxonomic groups. As part of its most recent registration decision for chlorfenapyr, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

chlorfenapyr is subject to the endocrine screening part of the Endocrine Disruptor Screening 

Program (EDSP). 

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

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

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

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

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

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

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

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

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

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

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

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

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of 
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chemicals identified for EDSP screening was published on June 14, 20132 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.3 

In this proposed interim decision, EPA is making no human health or environmental safety 

findings associated with the EDSP screening of chlorfenapyr. Before completing this 

Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination.

IV. PROPOSED INTERIM REGISTRATION REVIEW DECISION

A. Risk Mitigation and Regulatory Rationale

Ecological Risks:

The Agency has made a No Effects (NE) determination for chlorfenapyr under ESA section 7 for 

all listed species as well as a No Habitat Modification determination for all designated critical 

habitats for the currently registered uses. Also, no effects are expected for non-listed species. 

Therefore, no ecological risk mitigation for chlorfenapyr is being proposed by the Agency at this 

time.

Human Health Risks:

Non-cancer risks of concern from chlorfenapyr were identified for residential post-application 

exposure and occupational handler exposure. Risk mitigation for chlorfenapyr focuses on these 

two areas of concern. 

Mitigation for Residential Post-Application Risks of Concern

Residential post-application exposure assessments and aggregate exposure assessments

calculated that there was one residential chlorfenapyr use scenario with risks of concern: 

combined (post-application incidental oral, dermal, and inhalation) residential exposure for 

children (1 to <2 years old) from residential applications of chlorfenapyr using a coarse-stream 

application of product. The combined residential risk scenario for children 1 to <2 years old 

yielded an MOE of 62. When dietary exposure is added in to calculate aggregate risk, the MOE 

is 60.

In the human health risk assessment, EPA noted that if this use pattern was amended so that the 

chlorfenapyr product is applied using a pin-stream nozzle rather than a coarse-stream 

application, this scenario would no longer be a risk concern (MOE of 110). However, the 

chlorfenapyr registrant has proposed an alternative mitigation strategy. The registrant has 

proposed removing applications of chlorfenapyr to mattresses from all product labels. The 

Agency supports this action and is proposing the removal of chlorfenapyr mattress uses.

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

chemicals.

3 http://www.epa.gov/endo/
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With the removal of the mattress application, the combined residential risk estimate for indoor 

perimeter/spot/bed bug use for children (1 to <2 years old) increases from an MOE of 62 to 100 

and would no longer be of concern. The corresponding aggregate risk MOE will increase from 

60 to 92 after the removal of mattress uses. This MOE remains of concern since it is less than 

EPA’s LOC of 100.

To refine the aggregate risk assessment, the registrant proposed refining EPA’s dietary 

assessment for chlorfenapyr. EPA’s human health risk assessment for chlorfenapyr assumes

tolerance-level residues and a crop treatment factor of 100% for tomatoes, but chlorfenapyr is 

approved for tomato use only in greenhouses, not field-grown tomatoes. Based on USDA 

acreage data for field- and greenhouse-grown tomato, the registrant suggested that the percentage 

of US-grown tomatoes with the potential to be treated with chlorfenapyr is significantly less than 

100%.

However, tomato production per acre can be higher for greenhouse-grown tomatoes than for 

outdoor field-grown tomatoes. EPA found that in 2009, the most recent year for which 

production-based greenhouse tomato data were available, USDA’s Census of Horticulture 

Specialties reported that 3,207,177 hundredweights (cwt.) of tomato production occurred “under 

protection,” or in greenhouses. That value can be compared to 32,781,000 cwt. reported as the 

production of fresh market tomatoes “in the open” (grown in outdoor fields) in USDA’s National 

Agricultural Statistics Service (NASS) Vegetables Final Estimates 2008-2012. Assuming all 

greenhouse tomato production goes into the fresh market, about 8.9% of US fresh tomato 

production by weight is from greenhouses. Making the further assumption that all greenhousegrown tomatoes are treated with chlorfenapyr, an upper bound value for the percentage of 

tomatoes that are treated with chlorfenapyr can therefore conservatively be expected to be 8.9%, 

more than 11x lower than the 100% PCT value used in EPA’s dietary risk assessment for 

chlorfenapyr.

Although considering dietary risks is an important part of EPA’s risk assessment process for 

chlorfenapyr, the main exposure pathway driving risks of concern for chlorfenapyr is dermal. As 

stated above, with a 100% crop treatment factor for tomato and the cancellation of mattress uses 

for chlorfenapyr, the resulting aggregate risk MOE for children (1 to <2 years old) is 92. In 

addition to being influenced by the conservativeness of EPA’s dietary assessment for 

chlorfenapyr, this MOE value of 92 is also likely to be conservative given the nature of the 

dermal data currently available for chlorfenapyr.

The 13% dermal penetration factor used to calculate human health risk estimates for 

chlorfenapyr is derived from an in vivo rat dermal penetration study (MRID 49315901) that did 

not include tape stripping. Without tape stripping, all test material measured at the application 

site is included in the DAF calculation, potentially overestimating the amount of chemical that is 

bioavailable. The 13% DAF value used for chlorfenapyr does not incorporate either in vitro rat 

or in vitro human dermal absorption data, as these data are currently unavailable. DAF values 

derived solely from rat data tend to be more conservative than DAF values which incorporate 

data from dermal absorption studies conducted using human tissue. This is due to the higher 

permeability of rat skin relative to human skin.
15

Taking into consideration these factors characterizing the nature of chlorfenapyr’s dermal and 

dietary risks of concern, and after the removal of all mattress uses from chlorfenapyr labels, EPA 

is not proposing additional mitigation at this time to address residential risks from chlorfenapyr 

use.

However, the Agency notes that this safety finding for residential uses of chlorfenapyr (after the 

removal of mattress uses) is sensitive to small changes in EPA’s understanding of risks from this 

chemical. Because aggregate exposure to chlorfenapyr is right at the acceptable limit, EPA’s 

safety finding could be affected by minor changes to estimates of dietary consumption or postapplication residential exposure. Furthermore, the finding that chlorfenapyr’s current use pattern 

already reaches the maximum acceptable level of residential exposure at which EPA doses not 

expect unreasonable risks of adverse health effects from chlorfenapyr’s use (i.e. there is 

essentially a full “risk cup” for chlorfenapyr) means that no additional exposure scenarios (new 

uses) will be allowed for this chemical. 

Should the chlorfenapyr registrant wish to refine the residential risk estimate, the Agency advises 

that they select one or all of the following options:

1) The DAF used for calculating risk estimates for chlorfenapyr (13%) is currently based on 

an in vivo dermal penetration study conducted in rats with no tape stripping. As a result, 

all test material measured at the application site is included in the DAF calculation. A 

new study in rats could be conducted with tape stripping. Tape strips 1 and 2 are not 

included in current DAF calculations for chlorfenapyr since the material on these strips 

are considered non-penetrating. Therefore, a new study with tape strips could potentially 

reduce the DAF depending on the amount of test material found in tape strips 1 and 2.

2) The registrant could also consider submitting a dermal triple pack to refine the DAF, 

which consists of in vivo rat, in vitro rat, and in vitro human dermal absorption 

studies. The triple pack offers greater precision in estimating human dermal absorption 

by accounting for differences between in vitro and in vivo absorption rates, as well as for 

species differences between rats and humans. Should the registrant choose to conduct a 

dermal triple pack, all three studies in the triple pack should be conducted using identical 

protocols, test material, and doses. The registrants have already submitted an in vivo rat 

study, one of the three components of a dermal triple pack. This dermal penetration 

study (MRID 49315901) was used to calculate the 13% DAF used in EPA’s human 

health risk assessment for chlorfenapyr. Though EPA notes the tape stripping issue 

mentioned in the previous bullet point, MRID 49315901 was found to be an acceptable 

study for use in risk assessment.

3) The indoor surface residues used in the chlorfenapyr assessment represent default values 

taken from the Residential SOPs. The registrant could consider producing an indoor 

surface residue study that is representative of how chlorfenapyr will be used in a 

home. Such a study should be conducted so that it assesses indoor surface residues for 

multiple days after a chlorfenapyr application so that degradation/dissipation could be 

captured.

In all cases, the Agency recommends the registrant consult the Agency in their attempts to refine 

the chlorfenapyr risks, including submission of study protocols for review prior to conducting 

any study.
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Mitigation for Occupational Handler Risks of Concern

As described in the Chlorfenapyr - Preliminary Human Health Risk Assessment for Registration

Review, risks of concern are expected for certain short and intermediate-term occupational 

exposures for handlers.

For the use scenario of termiticide - crack and crevice treatment (EPA Reg. No. 499-548) using 

ready-to-use aerosol cans, gloves must be added to the PPE to reach a total MOE above EPA’s 

level of concern. Gloves are currently included as a PPE requirement all other chlorfenapyr enduse products except EPA Reg. No. 499-548. Current PPE on EPA Reg. No. 499-548, which 

includes a single layer of clothing (i.e. a long-sleeved shirt, long pants, and shoes plus socks, but 

no gloves or respirator), yields a total MOE of 56. If gloves are added, a total MOE of 130 will 

be reached and the use scenario will no longer be of concern.

• Mitigation Action: Gloves are proposed to be added to chlorfenapyr labelling permitting 

this use scenario.

For several handler risk exposure scenarios, additional PPE is needed on the Phantom® label 

(EPA Reg. No. 241-392) to reach MOEs greater than the LOC of 100. The submission of 

additional dermal data may impact the Agency’s future risk conclusions. Based on EPA’s 

current understanding of occupational risk from chlorfenapyr, the following PPE mitigation for 

chlorfenapyr (listed by use scenario) is proposed:

• Termiticide – Structural Treatment:

o For mixers/loaders/applicators (MLAs) of liquids using a mechanicallypressurized handgun for termiticide applications to structures, current levels of 

PPE yield combined MOEs below EPA’s level of concern4. This risk must be 

mitigated (to a total MOE of 120) by changing PPE for this labeled use scenario 

to include a double layer of clothing and gloves. The label currently requires 

gloves and a single layer of clothing.

 Mitigation Action: A double layer of clothing is proposed to be added to 

chlorfenapyr labels permitting this use scenario.

• General Crack and Crevice Treatment:

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

indoor environments such as residential living spaces, food handling 

establishments, and warehouses, the total MOE fails to exceed the LOC of 100 at 

baseline levels of PPE. The total MOE rises to 150 when PPE is amended to 

include a single layer of clothing, gloves and a PF5 respirator. The label currently 

requires gloves and a single layer of clothing.

 Mitigation Action: A PF5 respirator is proposed to be added to

chlorfenapyr labels permitting this use scenario. The Agency notes that 

label language for EPA Reg. No. 241-392 already includes a requirement 

that all termiticide handlers must wear a PF5 respirator when working in a 

non-ventilated space. This labelling amendment would expand that 

 4 Note that for this use scenario, table 9.1.1 in the 2014 human health risk assessment correctly presents the new 

MOE values with updated PPE, but the text in the bullet on pg. 35 incorrectly states single layer with gloves and 

PF5 respirator when it should say double layer with gloves and no respirator.
17

requirement to all crack and crevice treatment uses of the product, 

occurring in both ventilated or non-ventilated spaces.

Furthermore, for the use scenario of mixers/loaders/applicators of liquids using a mechanicallypressurized handgun for greenhouse applications to fruiting vegetables, there are risks of 

concerns (total MOE = 26) even with maximum PPE (i.e., double layer, gloves and PF10 

respirator). The registrant proposed mitigating this risk by increasing applicator PPE to a double 

layer of clothing with gloves plus a PF5 respirator, and by modifying application parameters to 

increase the spray dilution from 0.04 lb. ai/gallon to 0.013 lb. ai/gal. However, applying these 

measures would result in a combined MOE (dermal + inhalation) of 82, which still falls below 

the Agency’s LOC of 100. EPA is therefore proposing the removal of this use scenario from 

chlorfenapyr labels.

• Mitigation Action: The Agency proposes that all use scenarios of 

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

greenhouse applications to fruiting vegetables be removed from chlorfenapyr labels. 

Applicators wishing to perform greenhouse applications should substitute either a 

backpack or manually-pressurized handwand for a mechanically-pressurized handgun.

Comments are welcome from the public on all mitigation measures proposed for chlorfenapyr in 

this Proposed Interim Decision during the 60-day public comment period following the 

publication of this document. Comments are especially welcome from greenhouse production 

stakeholders. Again, these mitigation actions are based on EPA’s current understanding of risks

from chlorfenapyr. The submission of additional dermal data on this chemical may lead the 

Agency to reconsider its mitigation strategy.

B. Tolerance Amendments

Although EPA has determined that there are no adverse human health effects from all food uses 

of chlorfenapyr, the Agency will pursue changes to the tolerance classifications for chlorfenapyr 

due to updates in crop grouping. 

EPA will pursue the following changes to the tolerances of chlorfenapyr in 40 CFR § 180.513: 

• The existing tolerances for vegetable, fruiting group 8 (1.0 ppm) will be revised to 

vegetable, fruiting, group 8-10.

EPA will conduct rulemaking to implement these tolerance changes, in accordance with FFDCA.

C. Proposed Interim Registration Review Decision

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Proposed 

Interim Registration Review Decision. Except for the EDSP and pollinator components of this 

case, the Agency has made the following Proposed Interim Registration Review Decision: (1) no 

additional data are required at this time (though dermal data is recommended); and (2) changes 

to the affected registrations and their labeling are needed at this time.
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In this proposed interim registration review decision, EPA is making no human health or 

environmental safety findings associated with the EDSP screening of chlorfenapyr. The 

Agency’s final registration review decision for chlorfenapyr will depend upon the results of an 

EDSP FFDCA section 408(p) determination.

V. NEXT STEPS AND TIMELINE

A. Interim Registration Review Decision

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Proposed 

Interim Registration Review Decision, and placing it in the chlorfenapyr registration review 

docket (EPA-HQ-OPP-2010-0467) for public comment for 60 days. A Federal Register Notice 

will announce the availability of this Proposed Interim Registration Review Decision for 

chlorfenapyr and initiate a 60-day comment period. If there are no significant comments or 

additional information submitted to the docket during the comment period that leads the Agency 

to change its proposed interim decision, EPA will issue an Interim Registration Review Decision

for chlorfenapyr (case 7419). 

B. Implementation of Mitigation Measures

Registrants are to submit amended labels that include the label changes summarized in Section 

IV of this Proposed Interim Decision to the Agency within 60 days following issuance of the 

Interim Registration Review Decision in final form.