Docket Number EPA-HQ-OPP-2014-0341 

www.regulations.gov 

Picaridin 

Combined Work Plan, and Proposed Interim Registration 

Review Decision 

Approved by: 

Date: 

Case Number 7433 

December 2014 

~~p~~ 

Richard P. Keigwin,Jr. 

Director 

Pesticide Re-evaluation Division 

/~- 9·- ~01~ 

•,i,• 
Table of Contents 

Contents 

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

II. STATUTORY AND REGULATORY AUTHORITY ........................................... 4 

III. PICARIDIN CHEMICAL FACTS .. .. . .. . .. .. .... ........ .. ........ . .. . .................... . .. .. ... 5 

IV. USE AND USAGE INFORMATION .. ........ ... ................ ............................ .... 5 

V. RECENT ACTIONS ........... .. ... ....... .. . ................... .. .. ... . · . .. . .. ... . ..... ... .. ......... 6 

VI. SCIENTIFIC ASSESSMENTS .......... ......... . .. .... ..... . ........ . .. . ................. .. .. ... .. 6 

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

1. R.isk Conclusions .......................................................................................................................... 6 

- Hazard Characterization ............................................................................................................ 6 

- Dietary Assessment .................................................................................................................... 6 

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

- Occupational Assessment ......................................................................................................... 7 

- Aggregate Assessment ............................................................................................................... 7 

2. Human Health Incidents ............................................................................................................. 7 

3. Food Tolerances ................... : ....................................................................................................... 7 

B. Ecological Assessment ............................................................................................................................ 8 

1. Environmental Fate and Exposure ............................................................................................ 8 

2. R.isk Conclusions .......................................................................................................................... 8 

- Aquatic Organisms ..................................................................................................................... 8 

- Terrestrial Organisms .............................. : ................................................................................. 8 

3. Ecological Incidents ..................................................................................................................... 8 

C. Endangered Species Assessment ........................................................................................................... 9 

D. Endocrine Disruptor Screening Program ............................................................................... : ............ 9 

VII. COMBINED WORKPLAN AND PROPOSED INTRERIM REGISTRATION REVIEW 

DECISION . ... . ... ... .. .. .. .. ... .. . ............... .. .. .. . .. . .. . .. . .. . .. . .. . .. . ..... ..... . .. . ......... . 10 

- Tolerance Ammendments .... .. ... . ... ... ...... ... .. .. .............. . .. . .. . .. . .. ... ... . .. . ..... . .. 10 

- R.isk Mitigation and Rationale . ... ... ......... . .. .. .. ..... ... . ...... ................ . . .. .. . .. .. .. . . 10 

,.;_ - Interim Registration Review Decision .. .. .... .. . .. . .................... . .. . .. . .. . .. . .. . ..... . .... 10 

VIII. NEXT STEPS AND TIMELINE ..... .. . ..... . ........ . .. ... ... ... .......... ......... .. ... . ....... 1 0 

2 
References: 

Tlus document summarizes the Environmental Protection Agency's current position based on the 

following documents: 

1. Preliminary Environmental rate and Ecological Risk Assessment for the Registration Review of Picaridin. 

Brian Montague and Gabe Rothman. September 22, 2014. 

2. Picaridin Preliminary Human Health Risk Assessment in Support of Registration Review. Karlyn 

Middleton and Zaida Figueroa. December 5, 2014. 

3. Picaridin: Tier I Review of Human Incidents. Elizabeth Evans and Sharma Recore. February 11, 

2014. 

4. BEAD Chemical Profile for Registration Review: Picaridin. David Brassard, Cynthia Doucoure, and 

Derek Berwald. March 20, 2014. 

These and other supporting documents for the picaridin registration review case may be found in 

the docket EPA-HQ-OPP-2014-0341 at http://www.regulations.gov. 

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1. INTRODUCTION 

The docket for picaridin is now open, initiating the first public comment period for this 

registration review (docket number EPA-HQ-OPP-2014-0341). The Environmental Protection 

Agency's (EPA or the Agency) is issuing a combined Work Plan and Proposed Interim Registration 

Review Decision along with Preliminary Ecological and Human Health Risk Assessments for 

picaridin pursuant to 40 CFR Sections 155.50, 155.53, 155.56, and 155.58, followed by a sixty (60) 

day public comment period. This document explains what EPA's Office of Pesticide Programs 

knows about picaridin, highlighting assessment needs and providing an anticipated timeline for 

completing picariclin's review. These documents are being made available for public comment for a 

sixty (60) day period and can found in the docket EPA-HQ-OPP-2014-0341 at 

htq1 : I / www.rcgulntio ns.gov. 

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, a proposed interim 

registration review decision before completing a registration review. Among other things, the 

proposed interim registration review decision may require new risk mitigation measures, impose 

interim risk mitigation measures, identify data or information required to complete the review, and 

include schedules for submitting the required data, conducting the new risk assessment and 

completing the registration review. 

Picariclin is a broad-spectrum insect repellent registered for use against biting flies, chiggers, 

fleas, mosquitoes, and ticks. Picaridin is labeled for use on human skin and footwear. There is also 

one registered product for use on horses. Picariclin was first registered in the United States in 2000. 

Picaridin is not registered for any agricultural, non-agricultural, or greenhouse applications. For 

further information about picariclin, additional documents can be found in EPA's public docket 

(EPA-HQ-OPP-2014-0341) at W\Vw.regulations.gov. 

II. STATUTORY AND REGULATORY AUTHORITY 

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. 

All pesticides distributed or sold in the U.S. generally must be registered by EPA, based on scientific 

data showing that they will not cause unreasonable risks to human health or the environment when 

used as directed on product labeling. The registration review program is intended to make sure that, 

as the ability to assess risk evolves and as policies and practices change, all registered pesticides 

continue to meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided at www.cpa.gov /oppsrrdl /registration review/. 

The Agency is implementing the registration review program pursuant to Section 3(g) of 

FIFRA, and will review each registered pesticide every 15 years to determine whether it continues to 

meet the FIFRA standard for registration. The regulations governing registration review begin at 40 

CFR 155.40. The Agency will consider benefits information and data as requited by FIFRA. The 

public phase of registration review begins when the initial docket is opened for each case. The 

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docket is the Agency's opportunity to state what it knows about the pesticide and what additional 

risk analyses and data or information it believes are needed to make a registration review decision. 

III. PICARIDIN CHEMICAL FACTS 

Table 1: Chemical facts for Picaridin 

PC code 070705 

Case Number 7433 

CAS Number 119515-38-7 

Year fl.rst registered 2000 

Pesticide Type Insect repellent 

Chemical class Piperidine 

Reregistration Eligibility Because it was registered after November 1984, picaridin was not 

Decision (RED) subject to reregistration. 

Tolerance Reassessment Not applicable 

Eligibility Decision 

(IRED) 

Cumulative group Not applicable. The Agency has not determined that picaridin shares 

a common mechanism of toxicity with other chemical substances. 

40 CFR Citation There are no registered picaridin food/ feed uses and no established 

tolerances for picaridin 

Dual-use Conventional pesticidal uses only 

Non-pesticidal uses No non-pesticidal uses of picaridin 

Pesticide Re-evaluation Ricardo Jones, jones.ricardo@epa.gov, (703) 347-0493 

Division, Chemical Review 

Manager 

Registration Division, Kevin Sweeney, sweeney.kevin@epa.gov, (703) 305-5063 

Product Manager 

IV. USE AND USAGE INFORMATION 

Picaridin is reported to be widely used by consumers as an insect repellant. Picaridin is an 

alternative to DEET and is second after DEET in total U.S. use. Available data on picaridi.n show 

that it accounted for the 15% of total insect repellant consumption in 2009, and 14.33% of total 

consumption in 2011 (EPA Proprietary Data, 2010 and 2012). 

The use of insect repellents such as picaridin is intended to provide personal and public 

health benefits. Application of picaridin insect repellents to the skin is intended to help prevent bites 

from mosquitoes, ticks and other biting insects that may vector diseases such as Lyme disease, West 

Nile virus, malaria, yellow fever, dengue fever, and encephalitis. See the BEAD Chemical Profile for 

Registration Retliew: Picaridin in the registration review docket for more details. 

Summary of Use 

Table 2: Picaridin Use and Usage Information 

I For use on the human body and on horses to repel mosquitos, ticks, 

biting flies, deer flies, gnats, no-see-urns, chiggers and fleas. 

5 
Use Sites Picaridin is registered for use on human skin, hair, footwear, and 

horses. 

Summary of Usage Approximately 2.2 million lbs. of active ingredient were used in 

2009, and 2.1 million lbs. in 2011. 

Formulation Type(s) Formulations include aerosol or pump spray, towelettes/wipe, and 

cream/lotion. 

Application Method(s) Pi.caridin i.s generally applied using aerosol sprays, non-aerosol 

sprays, creams, lotions, and towelettes. 

Technical Registrant(s) Lanxess Corporation (39967) 

No. of Registrations 28 - FIFRA Section 3 registrations 

Restricted Use No 

V. RECENT ACTIONS 

There are no recent registration actions for picaridin. 

VI. SCIENTIFIC ASSESSMENTS 

A. Human Health Assessment 

The human health exposure and toxicological database is adequate for registration review of 

picaridin. The Agency does not need additional studies in order to characterize the human health 

exposure, hazard and risk from picaridin. Because no additional human health or toxicity data are 

needed for the registration review of picaridin, the Agency has determined that it is appropriate to 

conduct a preliminary human health risk assessment for picaridin. A summary of the Agency's 

preliminary human health risk assessment is presented below. For detailed discussions see: Picaridin 

Preliminary Human Health RiskAmssment in Support of Registration Review, dated December 5, 2014, in 

the public docket (EPA-HQ-OPP-2014-0341) which can be accessed at W\V\v.regulations.goY. 

1. Risk Conclusions 

I-:lazard Charaderization 

In previous assessments the Agency identified toxicological endpoints for picaridin. 

However, new toxicological data for picaridin indicate that the primary toxicological effects (in the 

kidney) observed in oral and dermal toxicity studies in rates are species specific, and are not relevant 

for humans. In addition, the Agency has reviewed the picaridi..n data base and using a weight-ofevidence approach, (i.e., considering physical, chemical characteristics, use and exposure), has 

determined that neither inhalation toxicity nor immunotoxicity data are required for picaridin 

(Hazard and Science Policy Council (HASPOC) 1XR# 0056905; Feb., 2013). Therefore, with no 

toXicological endpoints identified in the hazard database, a qualitative human health analysis is 

considered appropriate for picaridin. 

Dietary Assusment 

Picaridin is not registered for any food or· feed uses, and its use is not expected to 

contaminate drinking water; therefore no dietary (for or drinking water) analysis was completed. 

6 
Residential Assessment 

Picaridin is registered for use directly on human skin. Picaridin products can be applied 

several times in one day, and used for several days, weeks or longer depending on the personal 

activity pattern and/ or geographic area. Use is expected to result in both dermal and inhalation 

exposure, as well as incidental oral (hand-to-mouth) exposure. However, the toxicity database 

indicated no endpoints applicable to the oral, dermal, or inhalation routes of exposure. Therefore, a 

residential assessment for picaridin was not completed 

Occupational Assessment 

There is no occupational exposure associated with registered uses of picaridin. Therefore an 

occupational assessment for picaridin was not completed. 

Aggregate Assessment 

Because neither a dietary or residential assessment were completed, an aggregate assessment 

for picaridin was not completed. 

2. Human Health Incidents 

The Office of Pesticide Programs (OPP) Incident Data System (IDS) was used to retrieve 

pesticide incident data on picaridin. The IDS records incidents in one of two modules: Main IDS 

and Aggregate IDS. Main IDS contains incidents resulting in higher severity outcomes and provides 

more detail with regard to case specifics. Aggregate IDS contains incidents resulting in less severe 

human incidents (minor, unknown, or no effects outcomes). From January 1, 2009 to January 15, 

2014, there were 26 incidents involving picaridin reported in the database. These incidents were 

classified as moderate severity, not life threatening and the person returned to his/her pre-exposure 

state of health with no additional residual disability. In the Aggregate IDS, from January 1, 2009 to 

January 15, 2014, there were 214 reported incidents involving picaridin. These incidents were 

classified as minor severity a~d the symptoms resolved rapidly and usually involved skin, eye or 

respiratory irritation. 

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) databases were also queried. The NIOSH SENSOR-Pesticides 1998-2010 data 

identified 22 cases involving picaridin, 19 involving a single active ingredient and three involving 

multiple active ingredients. Of the 19 cases involving the single active ingredient, 18 cases were low 

in severity, largely involving dermal or eye irritation. One case was moderate in severity, and 

involved direct application of a product containing picaridin to the face of an infant. 

Reports of adverse health effects allegedly due to a specific pesticide exposure (i.e., an 

"incident") are largely self-reported and therefore, generally speaking, neither exposure to a pesticide 

or reported symptom (or the connection between the two) is validated or otherwise confirmed. 

Typically, causation cannot be determined based on incident data (Picaridin Preliminary Human Health 

Risk Assessment in Support of Registration Review, dated December 5, 2014). · 

3. Food Tolerances 

There are no U.S. tolerances established for picaridin because picaridin is not registered for 

any food or feed uses. 

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B. Ecological Assessment 

The ecological fate and ecotoxicity database is considered adequate for the registration 

review of picaridin. The Agency does not need additional studies in order to characterize the 

ecological exposure or hazard from picaridin. Because neither ecological fate nor toxicity data are 

needed for the registration review of picaridin, the Agency has determined that it is appropriate to 

conduct a preliminary ecological risk assessment for picaridin. A summary of the Agency's 

preliminary ecological risk assessment is presented below. For detailed discussions see Preliminary 

EntJironmental Fate and Ecological Risk Asmsment for the Registration Review of Picaridin, dated September 

22, 2014, in the public docket (EPA-HQ-OPP-2014-0341) which can be accessed at 

www.rcgulations.g<w . 

The Agency has completed a screening-level endangered and threatened (listed) species 

assessment for picaridin. The Agency is currently working with its federal counterparts and other 

stakeholders to implement an interim approach for assessing potential risk to listed species and their 

designated critical habitats. Once the scientific methods necessary to complete risk assessments for 

listed species and their designated critical habitats are fmalized, the Agency will complete its 

endangered species assessment for picaridin. Based on its registered use pattern, the Agency does 

not anticipate listed terrestrial species to come into contact with picaridin. Also, based on a 

conservative analysis, estimated risk quotients for aquatic species are far below levels of concern 

(LOCs). Therefore, the Agency anticipates making a "no effects" determination under the 

Endangered Species Act (ESA) for all listed species, and no adverse modification of designated 

critical habitat for such species is exp~cted, unless information provided to the Agency leads to a 

change in this anticipated determination. 

1. Environmental Fate and Exposure 

Picaridin is relatively stable, highly soluble in water, and does not easily volatilize. Based on 

tl1e use pattern and environmental fate properties of picaridin, significant environmental exposure 

(terrestrial or aquatic) is not expected. 

2. Risk Conclusions 

Aquatic Organisms 

The Agency estimated potential exposure and acute risk to aquatic organisms. The Agency 

completed conservative exposure estimates, and resulting acute risk quotients (R.Qs) are far below 

the Agency's level of concern. While chronic RQs were not estimated, given the large margin of 

safety observed for acute effects, the Agency believes it unlikely that chronic risks would approach 

concern levels. SinWarly, risk to aquatic plants is presumed to be below the level of concern based 

on picaridin's low toxicity and low potential to enter aquatic environments. 

Terrestrial Organisms 

Based upon the use pattern of picaticlin, the Agency does not expect a terrestrial exposure 

pathway to exist, and therefore, no terrestrial risk analysis was conducted. 

3. Ecological Incidents 

There are no reported incidents involving picaridin. A review of all available information in 

the following databases was completed in March 2014: Ecological Incident Information System 

8 
(EllS), Aggregate Incident Reports database, Avian Monitoring Information System (AIMS), the 

Contaminant Exposure and Effects - Terrestrial Vertebrate (CEE-TV), or the OPP Incident Data 

System (IDS). For additional discussion of the reported ecological incidents, see the Preliminary 

Environmental Fate and Ecological Risk Assessment for the Registration Review rfPicaridin. 

C. Endangered Species Assessment 

Based on the lack of exposure potential, and low risk potential of picaridin, the Agency 

concludes that effects on the environment are not reasonably expected to occur from the registered 

use of picaridin. Therefore, the EPA anticipates making a "no effects" determination under the 

Endangered Species Act (ESA) for all listed species and that no adverse modification of designated 

critical habitat for such species is expected from the registered use of picaridin, unless information 

provided to the Agency leads the Agency to change its anticipated determination. 

C. 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 picaridin, EPA reviewed these data and determined that a 

qualitative toxicity assessment is appropriate for picaridin. However, as required by FFDCA section 

408(p), picaridin is subject to the endocrine screening part of the Endocrine Disrupter 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 fust group of 67 

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

9 
chemicals identified for EDSP screening was published on June 14, 20131 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 disrupters. 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 

In the interim, EPA is making no human health or environmental safety findings associated 

with the EDSP screening of picaridin. Before completing this Registration Review, the Agency will 

make an EDSP FFDCA section 408(p) determination. 

VII. COMBINED WORK PLAN AND PROPOSED INTERIM REGISTRATION 

REVIEW DECISION 

Tolerance AmendmentJ 

There are no U.S. tolerances established for picaridin, and so the Agency will not pursue any 

tolerance actions with picaridin. 

RiJk Mitigation and Rationale 

The Agency has identified no human health or ecological risks associated with registered 

uses of picaridin. Therefore, the Agency did not identify the need to modify the current registered 

use of picaridin. 

Interim RegiJtration Review DeciJion 

In accordance with 40 CFR Sections 155.50, 155.53, 155.56, and 155.58, the Agency is 

issuing this combined Work Plan and Proposed Interim Registration Review Decision along with 

Preliminary Hwnan Health and Ecological Risk Assessments. Except for the EDSP component of 

the picaridin registration review case, the Agency has made the following interim decision: (1) no 

additional data are required at this time; a~d (2) no changes to the affected picaridin registrations or 

their labeling are needed at this time. Currently registered uses of picaridin are not expected to result 

in adverse effects for listed and non-listed species, or critical habitat. As such, EPA expects to 

conclude ''no effect" for listed species and no adverse modification of designated critical habitat for 

all currently registered uses of picaridin, unless information provided to the Agency leads the Agency 

to change its anticipated determination. 

VIII. NEXT STEPS AND TIMELINE 

A Federal Register Notice will announce the availability of this combined Work Plan, 

Proposed Interim Registration Review Decision, and Preliminary Ecological and human Health Risk 

Assessments for picaridin and allow a 60-day comment period for this combined document as well 

as the two preliminary risk assessments. 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 decision, EPA may issue an Interim Registration Review Decision for picaridin (case 

7433). However, a fmal decision for picaridin may be issued without having previously issued an 

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

chemicals. 

2 http://www.epa.gov/endo/ 

10 
interim decision. A final decision on the picaridin registration review case will occur after an EDSP 

FFDCA section 408(p) determination has been made. 

EPA has created the following estimated timeline for the completion of picaridin's 

registration review. 

Registration Review for Picaridin- Projected Registration Review Timeline 

Activities Estimated Date 

Open Public Docket and Public Comment Period for Combined Work 2014 - December 

Plan, and Proposed Interim Registration Review Decision along with 

Preliminary Human Health and Ecological Risk Assessments 

Close Public Comment Period 2014- February 

Interim Registration Review Decision and Begin Post-Decision Follow- 2014 - June 

up3 

Total (years) 0.5 

3 A final decision on the picaridin registration review case, in accordance with 40 CFR Section 155.158, will occur 

a fter an EDSP FFDCA section 408(p) detennination has been made. 

11