Docket Number EPA-HQ-OPP-2014-0341 

www.regulations.gov 

Picaridin 

Interim Registration Review Decision 

Case Number 7433 

June 2015 

Approved by: ~ ~ ,)J 

Richard P. Keigwin, Jr. 

Director 

Pesticide Re-evaluation Division 

Date: 0/ /c 01~ 
I. Introduction 

This document is the Environmental Protection Agency's (EPA or the agency) Interim 

Registration Review Decision for picaridin 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 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. For further information on picaridin, 

additional documents can be found in EPA's public docket (EPA-HQ-OPP-2014-0341) 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 reevaluates 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/oppsrrdl/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. All relevant documents and comments 

received with regards to the registration review of picaridin can be found in the public docket at: 

EPA-HQ-OPP-2014-0314, accessible at www.regulations.gov. 

Picaridin 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 horse and rider. Picaridin 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 picaridin, additional documents can be 

found in EPA's public docket (EPA-HQ-OPP-2014-0341) accessible at www.regulations.gov. 

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

picaridin (case 7433). The following highlights significant events that have occurred during the 

registration review of picaridin: 

• December 24, 2014 - Issuance of Picaridin Preliminary Human Health Risk Assessment, 

Preliminary Environmental Fate and Ecological Risk Assessment for the Registration 

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Review of Picaridin, Picaridin Combined Work Plan, and Proposed Interim Registration 

Review Decision for a 60-day public comment period. 

o The Combined Work Plan and Proposed Interim Registration Review Decision 

noted that no additional data were anticipated to be needed for the picaridin 

registration review because sufficient information was available to conduct risk 

assessments to support a registration review decision. 

o Two comments were submitted to the agency during the 60 day public comment 

period for the picaridin Combined Work Plan and Proposed Interim Registration 

Review Decision. Neither comment modified the work plan for picaridin. 

• Comment Submitted by the Center for Biological Diversity (CBD) in 

EPA-H Q-0PP- 2014- 0341-0010: 

Given the use pattern for picaridin, CBD concurs with the EPA's 

assessment that there is no reasonable expection of adverse effects 

to endangered and threatened species or to listed species' critical 

habitat. 

• EPA Response: 

The agency thanks the CBD for its comments. 

• Comment Submitted by Lanxess Corporation in EPA HQ- OPP-2014-

0341-0011: 

The technical registrant, Lanxess, noted that their technical 

registration is unconditional rather than conditional. They also 

noted that the maximum number of applications for two labels was 

incorrectly described as two per year, rather than two per day. 

• EPA Response: 

The agency acknowledges and corrects the following errors: the 

Lanxess registration for KBR 3023 is unconditional; labels Reg. 

Nos. 39967-50 and 39967-53 correctly direct a maximum 

application of twice per day. 

Additional information on picaridin can be found in EPA's public docket, EPA-HQ-OPP2014-0341 , which can be accessed at www.regulations.gov. 

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II. Scientific Assessments 

A. Human Health 

At the outset of the registration review for picaridin, the agency reviewed the existing 

risk assessments and database for picaridin and determined that no new data were required to 

characterize the human health exposure, or hazard from picaridin. As a result, the agency 

combined the scoping of the human health risk with the qualitative risk assessment. A summary 

of the agency's human health risk assessment is presented below. For detailed discussions see: 

Picaridin Preliminary Human Health Risk Assessment, dated December 5, 2014, in the public 

docket (EPA-HQ-OPP-2014-0341) which can be accessed at www.regulations.gov. 

1. Human Health Risk Summary 

In previous assessments the agency identified toxicological endpoints for picaridin. 

However, toxicological data received prior to the registration review for picaridin indicated that 

the toxicological effects (in the kidney), observed in oral and dermal toxicity studies in rats, were 

species specific and not relevant for humans. In addition, the agency has reviewed the picaridin 

database using a weight-of-evidence approach, (i.e., considering physical, chemical 

characteristics, use and exposure), and determined that neither inhalation toxicity nor 

immunotoxicity data were required for picaridin (Hazard and Science Policy Council (HASPOC) 

TXR# 0056905; Feb., 2013). Therefore, with no toxicological endpoints identified for picaridin, 

a qualitative human health analysis was completed. 

Dietary Assessment 

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

contaminate drinking water; therefore no dietary (food or drinking water) analysis was 

completed. 

Residential and Occupational Assessment 

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

up to several times in one day, and be 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, since no 

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human health toxicity endpoints had been identified in the picaridin database, neither residential 

nor occupational assessments were conducted. 

Aggregate Assessment 

Because neither a dietary nor residential assessment were completed, an aggregate 

assessment for picaridin was not completed. 

Food Tolerances 

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

for any food or feed uses. 

2. Human 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 and 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 RiskPesticides (SENSOR) databases were also queried. The NIOSH SENSOR-Pesticides 1998-2010 

data identified 22 cases involving picaridin, 19 with the single active ingredient picaridin and 

three with multiple active ingredients. Of the 19 cases the single active ingredient picaridin, 18 

cases were of low severity, largely involving dermal or eye irritation. One case was of moderate 

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

The agency notes that 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). 

B. Ecological 

Upon review of the existing risk assessments and database for picaridin, the agency 

determined that no new data were required to characterize the ecological risk from picaridin. As 

a result, the agency combined the ecological problem formulation with the qualitative 

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preliminary risk assessment for picaridin. A summary of the agency's preliminary ecological risk 

assessment is presented below. For detailed discussions see: Priliminary Environmental Fate and 

Ecological Risk Assessment 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.regulations.gov. 

1. Environmental Fate and Exposure 

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

current use pattern for picaridin (i.e. applied to humans and horses) limits exposure to non-target 

organisms, and environmental exposure (terrestrial or aquatic) is expected to be minimal. 

2. Risk Conclusions 

Aquatic Organisms 

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

exposure estimates, and resulting acute risk quotients (RQs) 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. 

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 picaridin, the agency does not expect a terrestrial exposure 

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

3. Ecological Incidents 

There are no reported incidents involving picaridin in any of the incident data bases 

accessable to the agency. A review of all available information in the following databases was 

completed in March 2014: Ecological Incident Information System (EIIS), 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 of Picaridin, dated September 

22, 2014. 

III. Risk Characterization 

A. Endangered Species Assessment 

The agency's registration review ecological risk assessment for picaridin also constitutes 

an endangered and threatened (listed) species assessment for picaridin. Based on its registered 

use pattern and lack of a complete exposure pathway, the agency does not anticipate listed 

terrestrial species to be affected by picaridin. Further, the agency conducted a conservative 

quantitative analysis for aquatic species, and found that estimated RQs are far below LOCs. 

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Therefore, for direct effects from picaridin, the agency is making a "no effect" determination 

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

critical habitat for such species. The agency anticipates conducting no further analysis of 

potential risks to endangered or threatened species unless data or information are obtained that 

would otherwise inform this determination. 

B. Endocrine Disruptor Screening Program 

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

adverse outcomes from exposure to picaridin. 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 selected the most sensitive endpoints for relevant risk assessment 

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

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

hormonal systems. Compounds 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 

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

of compounds identified for EDSP screening was published on June 14, 2013 1 and includes some 

pesticides scheduled for Registration Review and compounds found in water. For further 

information on the status of the EDSP, the policies and procedures, future lists, the test 

guidelines, and the Tier 1 screening battery, please visit our website. 2 

1 http://www.regu lations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074. 2 http://www.epa.gov/endo/ 

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In this interim decision, 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. 

IV. Interim Registration Review Decision 

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

Interim Registration Review Decision. At this time the agency does not anticipate the need to 

require any further data, including pollinator data, for picaridin. Except for the EDSP component 

of the picaridin registration review case, the agency has made the following interim decision. 

• No changes to the affected picaridin registrations or their labeling are needed. 

• No additional data are required. Pollinator studies have not been required for 

picaridin. However, with the June 2014 Guidance for Assessing Pesticide Risks to Bees3 

now in place, EPA has begun to require these data where applicable. Consistent with 

existing guidance 40 CFR, Part 158, Subpart G § 158.630, pollinator data are required for 

pesticide active ingredients with terrestrial, forestry and residential outdoor uses. Based 

upon the use pattern for picaridin and the lack of a complete terrestrial exposure pathway, 

EPA will not require pollinator data at this time. 

• Under the ESA, for direct effects from picaridin, the EPA is making a determination of 

"no effects" for all listed species and no adverse modification of designated critical 

habitat for such species. 

V. Next Steps and Timeline 

A. Interim Registration Review Decision 

Based upon the agency's conclusions for picaridin under registration review and the 

ESA, no actions are required at this time for this interim registration review decision. 

B. Final Registration Review Decision 

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

FFDCA section 408(p) determination has been made. 

3 http://www2.epa.gov/sites/production/fi les/20 1406/documents/pollinator risk assessment guidance 06 19 14.pdf 

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