Docket Number EPA-HQ-OPP-2014-0 341 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 ofpicaridin 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 ofpicaridin:

• December 24 , 2014

- Issuance ofPicaridin Preliminary Human Health RiskAssessment , Preliminary Environmental Fate and Ecological RiskAssessment for the Registration

2Review 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

-HQ-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 oftwice 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 ofthe 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 ofthe human health risk with the qualitative risk assessment. A summary ofthe agency ' s human health risk assessment is presented below. For detailed discussions see: Picaridin Preliminary Human Health RiskAssessment, 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

4human health toxicity endpoints had been identified in the picaridin database , neither residential nor occupational assessments were conducted. Ag gregate 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 ofPesticide Programs (OPP) Incident Data System (IDS) was used to retrieve pesticide incident data on picaridin. The IDS records incidents in one oftwo 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 ofhealth 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. Ofthe 19 cases the single active ingredient picaridin, 18 cases were of low severity, largely involving dermal or eye irritation. One case was ofmoderate 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 ofthe 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

5preliminary risk assessment for picaridin. A summary ofthe agency's preliminary ecological risk assessment is presented below. For detailed discussions see: Priliminary Environmental Fate and Ecological RiskAssessment 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
A quatic 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 ofpicaridin, 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 ofthe 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 ofthe reported ecological incidents, see the Preliminary Environmental Fate and Ecological RiskAssessment 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.

6Therefore , 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 ofthe 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 ofthe EDSP where EPA will determine which, if any , ofthe 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 ofthe EDSP, the policies and procedures , future lists , the test guidelines, and the Tier 1screening battery, please visit our website. 2

1 http: //www .regu lation s.gov/# !documentDetail;D=EPA-HQ-OPPT

-2009 -0477 -0074. 2 http ://www .epa.gov/endo/
7In this interim decision, EPA is making no human health or environmental safety findings associated with the EDSP screening ofpicaridin. 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 ofthe 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 Guidancefor Assessing Pesticide Risk s to Bees 3
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 1 406/documents/po llin ator ri sk assessment gui dance 06 1 9 14.pdf
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