### Page 2 of 45



# Environmental Fate and Ecological Risk Assessment for the Registration Review of Picaridin

1

- piperidinecarboxylic acid 2

- (2

- hydroxyethyl)

- 1

- methylpropylester

( Pi caridin, CAS 119515

- 38

- 7 )

Prepared by: Brian Montague

, Fishery Biologist Gabe Rothman

., Environmental Scientist U. S. En vironmental Protection Agency Office of Pesticide Programs Environmental Fate and Effects Division Environmental Risk Branch IV 1200 Pennsylvania Ave., NW Mail Code 7507P Washington, DC 20460 Reviewed by: Al V au ghan , RAPL Justin Housenger, Biologist Micha el Barrett, Senior Chemist Mah Shamim , Branch Chief

### Page 3 of 45 Table of Contents

1. Executive Summary

................................ ................................ ................................ ................... 4 1.1 Nature of Chemical Stressor

................................ ................................ ................................ 4 1.2 Potential Risks to Non

- target Organisms

................................ ................................ ......... 4 1.3 Conclusions

- Exposure Characterization

................................ ................................ ........ 5 1.4 Conclusions

- Effects Characterization

................................ ................................ ............ 6 2. Use Characterization

................................ ................................ ................................ .................. 6 2.1 Nature of the Che mical Stressor

................................ ................................ ....................... 6 2.2 Overview of Pesticide Usage

................................ ................................ ........................... 7 3. Environmental Fate and Transport Characterization

................................ ................................ .. 7 3.1 Transport in the Environment

................................ ................................ .......................... 8 3.2 Degradation in t he Environment

................................ ................................ ...................... 9 4. Ecological Toxicity Characterization

................................ ................................ ......................... 9 4.1 Effects to Aquatic Organisms

................................ ................................ ........................ 10 4.2 Effects to Terrestrial Organisms

................................ ................................ .................... 11 4.3 Degradate toxicity

................................ ................................ ................................ .......... 11 4.4 ECOTOX Open Literature

................................ ................................ ............................. 11 5. Problem Formulation

................................ ................................ ................................ ................ 12 5.1 Conclusions from Previous Risk Assessments

................................ .............................. 12 5.2 Conceptual Model

................................ ................................ ................................ .......... 12 5.3 Analysis Plan

................................ ................................ ................................ .................. 13 5.4 Endangered Species Assessment

................................ ................................ .................... 16 5.5 Endocrine Disruptor Screening Program

................................ ................................ ....... 16 6. Exposure Analysis

................................ ................................ ................................ .................... 17 6.1 Estimated Surface Water Concentrations

................................ ................................ ....... 17 6.2 Monitoring Data for Picaridin

................................ ................................ ........................ 20 6 .3 Terrestrial Exposure Analysis

................................ ................................ ........................ 20 7. Risk Characterization

................................ ................................ ................................ ............... 20 7.1 Risk Estimation

................................ ................................ ................................ .............. 20 7.2 Risk Descrip tion

................................ ................................ ................................ ............. 22 7.3 Uncertainties, Limitations, and Data Gaps

................................ ................................ ..... 22 8. Federally Threatened and Endangered (Listed) Species Concerns

................................ .......... 23 9. References

................................ ................................ ................................ ................................ 25

### Page 4 of 45



## 1. Executive Summary

1.1 Nature of Chemical Stressor

Registration review is being performed for the insect repellent picaridin ( 2

- (2

- Hydroxyethyl)

- 1

- piperidinecarboxylic acid 1

- methylpropyl ester ). This document contains the problem formulation as well as the environmental fate, ecological risk, and endangered species assessmen ts for its registered uses. T his risk assessment is intended to identify ecological risk s associated with the registered uses of picaridin

. Picaridin is a broad spectrum insect and tick repellent used on the human body and clothing (skin, hair, clothin g, footwear, shoes, and headgear/caps). Picaridin is used to repel biting flies, mosquitoes, chiggers, ticks, and fleas. Picaridin was first registered in the United States in 2000

. Picaridin is not registered for any agricultural, non

- agricultural, or greenhouse applications nor has it been registered as a pesticide before this time . It is also not registered for any home, residential, or indoor applications nor is it a known byproduct of any kind from industrial manufacturing or refining processes. P icaridin is applied to human skin and hair, worn clothing, footwear, and headgear, or horse skin.

Currently, picaridin is formulated as a pressurized spray (aerosol)

, as impregnated materials (e.g. towelettes, roll

- on), and as a ready

- to

- use s olution (n on aerosol pump spray, liquid, cream, lotion, or foam ). Picaridin concentrations in end

- use products range from 5 to 20 % a.i

.



## 1.2 Potential Risks to Non

- target Organisms

The results of this assessment on currently registered picaridin uses indicate that the re are no acute RQs that exceed the LOC to listed or non

- listed non

- target organisms ( Table 1.1 ). Additionally, the Agency has determined that there is no habitat modification of any designated critical habitat for listed species from the current registere d uses of picaridin

. Conclusions regard ing aquatic organisms are based on lack of RQs that exceed the acute LOC in the risk estimation

. Conclusions regarding terrestrial organisms and plants are based on the lack of a complete exposure pathway. Exposure in terrestrial habitats would be limited to human skin, clothing, and shoes, as well as horse skin and hair. Products formulated as lotions or impregnated wipes would be applied directly to the human skin. Many other product labels specify recommended spra y distances of less than 10 inches from the intended application sites (human skin, clothing, and shoes, as well as horse skin and hair). Exposure to listed species is not expected because they would not likely come in close contact with humans or domestic horses ( i.e., the registered use sites). Even if a non

- target organism were to come into contact with picaridin from

over

- spray , exposure lev els would be expected to be low. T herefore, given its low toxicity profile, effects to non

- target organisms would not be anticipated to exceed concern levels even if exposure occurred.

### Page 5 of 45

Table 1.1. Potential Effects to Federally Listed Taxa Associated with Direct or Indirect Effects from the Currently Registered Uses of Picaridin

Listed Taxon Direct Effects Indire ct Effects
Terrestrial and semi

- aquatic plants

- monocots

No No Terrestrial and semi

- aquatic plants

- dicots

Birds Terrestrial

- phase amphibians and reptiles

Mammals Terrestrial invertebrates Aquatic nonvascular plants Aquatic vascular p lants Freshwater fish Aquatic

- phase amphibians Freshwater invertebrates Marine/estuarine fish Marine/estuarine invertebrates



## 1.3 Conclusions

- Exposure Characterization

Picaridin possesses soil

- water partition coefficient values (estimated Koc = 64

- 389 mL/g) tha t are consistent with pesticides which are known to remain in the water column to a certain extent. Therefore, picaridin can remain in the water column to a large extent once washed off from treated human skin which may be in cont act within water bodies. In surface waters, p icaridin is expected to degrade to some extent as evident from a degradation laboratory study using water monitoring samples in a waste water stream (Knepper, 2004). The laboratory study analysis indicates tha t picaridin degrades to the principle degradate picaridin carboxylic acid, which occurs mainly through multiple oxidation processes. Picaridin is lipophilic and therefore has the potential to partition to fish tissue to some extent . However, substantial bioaccumulation of residues is not expected consideri ng the nature of applications with picaridin to mainly human subjects, indications of its high depuration based on low BCF values, and low aquatic concentrations expected in the environment. Picaridin’s low toxicity and low persistence further suggests that any small level of bioaccumulation which occurs would have a low impact on aquatic organisms.

Aquatic exposure estimates for picaridin are based on washoff after application to skin or clothing
or to horses. Upper

- bound aquatic estimated exposure concentrations (EECs) ranged from 0.00 17 to 0.081 mg a.i./L (17 to 81  g a.i./L) depending on the number of individuals entering a 2 0 ,000,000 L water body (standard farm pond). Surface water m onitoring data in influent wastewater streams varied between 0.6

– 1.4  g/L ( Knepper, 2004 ). The upper

- bound EEC of 81
 g/L was betw een one and two orders of magnitude higher than the highest monitoring concentration.

Exposure to terrestrial non

- target organisms and plants is expected to be inconsequential based on the labeled use patterns.

### Page 6 of 45



## 1.4 Conclusions

- Effects Characterization

Th e agency has reviewed a reduced data set for picaridin consisting of one subacute dietary toxicity study with an avian species and 3 acute toxicity studies with a fish, aquatic invertebrate, and freshwater algae.

Aquatic Organisms

Technical grade picarid in is classified as practical ly non

- toxic to fish ( which serve as surrogates for aquatic

- phase amphibians )

. The 96 hour LC 50 

### for Rainbow trout ( Oncorhynchus mykiss ) was determined to be 173 mg a

. i/ L (MRID 44408740)

. Picaridin is practically non

- toxic to aquatic invertebrates

. Toxicity to aquatic invertebrates was observed to be low for the Water flea, Daphnia magna

, with a 48 hour EC 50 

### and NOAEC > 103 mg ai/L (MRID 44408741). Effect levels to the freshwater green algae, Scenedesmus subspicatus was ob served to be a 72 hour EC 50 

### of 87 mg ai/L and a NOAEC of 54.8 mg ai/L (MRID 44408742).

Toxicity data were not available for evaluation of picaridin chronic exposure to freshwater fish and invertebrates. No toxicity data were available for estuarine/mari ne fish and invertebrates or for vascular aquatic plants.

Terrestrial Organisms

P icaridin is practically non toxic to birds on a subacute dietary exposure basis. In a 5 day dietary exposure to Bobwhite quail, Colinus virginianus no mortality or adverse behavioral effects were observed at 5000 mg ai/ k g

– diet treatment group. (MRID 44408739)

.

Picaridin is slightly toxic (Category III) to mammals o n an acute oral exposure basis with LD 50 

### ’s of 2236 and 4743 mg ai/Kg for male rat (fasted and non

- fasted

, resp ectively

, MRID 44408705 )

. In a 14 week feeding study the subchronic LOAEL was determined to be 1033 mg/Kg/day for labor atory rats based on decreased b ody weight in males and females and effects to male k idneys including increased weig ht and nephropathy. No developmental toxicity was observed at up to 400 mg/Kg/day in laboratory rats (MRID 45387902)

. No toxicity data were available for non

- target insects or terrestrial plants.



## 2. Use Characterization

2.1 Nature of the Chemical Stressor

Picaridin belongs to t he chemical class of piperidine s ( US EPA, 2005). The specific mechanism of action of p icaridin has not been determined. However, r ecent mosquito behavior research suggests that repellency is due to direct detection of picaridin by the olfactory receptor ne urons (ORNs) in the antenna, which appears to prevent the mosquito from recognizing the host (Klun, et al., 2006). Other research has suggested that mosquito response to picaridin var ies by individual mosquitos and mosquito species (Amer and Mehlhorn, 200 6) . The efficacy of the repellency of picaridin was reduced in some individual mosquitos where the maxillary bulbs did not exist. Furthermore,

### Page 7 of 45

Anopheles stephensi mosquitoes appeared to sense picaridin while also maintaining the ability to recognize the host using different organs (Amer and Mehlhorn, 2006). Direct exposure to picaridin did not kill or alter the behavior of mosquitoes (Licciardi, 2006).



## 2.2 Overview of Pesticide Usage

There are a total of 28 active registrations with picaridin . All product s possess the single active ingredient (a.i.)

. Most are registered under the trade name of “Cutter” insect repellents and sold by the Spectrum Division of United Industries, Inc

. The p ercent a.i. in the ready

- to

- use products ranges from 5 to 20%. Picari din is applied on the human body and clothing (skin, hair, clothing, footwear, shoes, and headgear/caps). Picaridin is used to repel biting flies, mosquitoes, chiggers, ticks, and fleas. Picaridin may also be applied to horse skin. The approved pests as sociated with picaridin uses are: biting flies, mosquitoes, chiggers, ticks, and fleas. The physical forms of the

re gistered products include ready

- to

- use solutions, impregnated substances on to welettes, aerosols
sprays, and other pumps and sprays. The f oll owing list provides a summary o f all available formulations for picaridin , all of which have identical uses:

 Pumps and sprays: 5% and 7% a.i

.

 Aerosol sprays: 10%, 12%, 15%, and 20% a.i

.

 Impregnated substance: 5.75%, 10%, 16%, and 20% a.i

.

 Ready

- to

- u se solutions: 5%, 10%, 15%, and 20% a.i

.

 Technical grade substance : 98.7% a.i

. A more detailed table of picaridin p roducts is provided in Appendix C

. 

## 3. Environmental Fate and Transport Characterization

Picaridin is an all

- purpose insect repellent in the piperidine chemical class. It is a racemic mixture of two diastereoisomers that occur in roughly equal proportions (WHO, 2004 ). Some piperidine compounds are indigenous to extracts from pepper plants. However, picaridin is in itself a synthetic compound (Moore and Debboun, 2007) . The technical substance of picaridin is a nearly colorless and odorless liquid (EPA, 2005). It is relatively stable and highly soluble in water (WHO, 200 4 ). The physicochemical characteristics associated with picaridin are s ummarized in Table 3.1

.

Table 3.1. Ph ysicochemical properties of picaridin

. Parameter Value Citation

Structure EpiSuite

Molecular f

ormula C 12 H 23 NO 3 MRID 466620 0 1

### Page 8 of 45

Table 3.1. Ph ysicochemical properties of picaridin

. Parameter Value Citation Molecular w eight 229 .3 g/ mol MRID 466620 0 1 CAS Number: 119515

- 38

- 7 CAS Name: 2

- (2

- Hydroxyethyl)

- 1

- piperidinecarboxylic acid 1

- methylpropyl ester Density 0.909 g/ m L MRID 46662001

Water s olubility 8.2 x 10 3 mg/L at 2 0 °C , pH 4

- 9 196 mg/L at 2 5 °C , pH7 WHO, 200 4 EpiSuite, WSKOW v.1.41 Vapor pressure 4.40 x 10

- 4 torr @ 2 5 °C WHO, 200 4 Henry’s law constant 3.0 x 10

- 11 atm

- m 3 /mol @ 2 5 °C SRC Database 1
Soil sorption c oefficient (K oc ) 64.43 mL/g 389 mL/g EpiSuite, KOCWIN v.2.00 SRC Database 1 Octanol

- water partition c oefficient (log K ow ) 4.94 MRID 46662001

Bioconcentration f

actor (BCF) in fish 23.05 L/kg E pi Suite

, BCFBAF v.3.01

1 Available on

- line: http://www.srcinc.com/what

- we

- do/environmental/scientific

- databases.html



### . 

## 3.1 Transport in the Environment

Picaridin is expected to remain dissolved in water given its high solubil ity value of 196 mg/L. Furthermore, picaridin ’s Henry’s Law Constant value of 3.0 x 10

- 11 

### atm

- m 3 

### /mol indicates that it will not volatilize under moist conditions. Under dry conditions, picaridin is moderately volatile given its vapor pressure value of 4 .40 x 10

- 4 

### torr. However, volatilization of picaridin is not expected to occur to a large extent.

Once picaridin is washed off from treated human or horse skin, picaridin is expected to remain in the water column to a ceratin extent ( estimated K oc 

### value s between 64

- and 389 mL/g ). However,
p i caridin ’s K ow 

### value of 4.94 also suggests that picaridin is lipophilic and may tend to bioconcentrate in fish tissue to some extent . However, the bioconcentration factor of picaridin is relatively small suggesting t hat a notable amount of picaridin may e xist in water under steady state conditions surrounding aquatic animals considering processes such as depuration. Furthermore,
upper

- bound EECs in water are expected to be very low, as shown in Table 6.2 of Section 6 .1

. Low monitoring concentrations of picaridin, shown in Section 6.2 , in stream water confirm this. Therefore, bioaccumulation is not expected to be prevalent for picaridin considering the low expected concentrations indicated by its use pattern and low BCF value.

### Page 9 of 45



## 3.2 Degradation in the Environment

The only environmental fate study submitted to the Agency is the hydrolysis study (MRID No. 44408743 ). The study demonstrated that picaridin is stable to hydrolysis in solutions initially buffered to pH 5, 7, and 9 over 30 days

. However, there is evidence that picaridin can degrade in the environment. Extracts from m onitoring data in effluent water from a wastewater treatment plant in Germany indicates that picaridin degrades to the principle degradate picaridin carboxylic acid in the environment (Knepper, 2004) , and its chemical structure shown in Figure 1 below

. The chemical degradation model Catabol 301c 1 

### indicates that this process occur s due to multiple oxidation processes which is a known process which ma y occur naturally in the environment

. Therefore, the results from Catabol 301c demonstrate that it is plausible for picaridin carboxylic acid to form without any influence from wastewater treatment , although its formation as observed in the Knepper study may have been enhanced by the wastewater plant

. The Catabol 301c analysis and predicted environmental degradation pathway of picaridin is shown in Appendix D of this document.

Figure 1. Chemical structure of picaridin carboxylic acid (molecular weight = 242 g/mol).



## 4. Ecological Toxicity Characterization

In screening

- level ecological risk assessments, effects characterization describes the types of effects a pesticide can have on aquatic and terrestrial organisms. . B irds are used as surrogates for rep tiles and terrestrial

- phase amphibians and freshwater fish are used as surrogates for aquatic

phase amphibians. This characterization is based on the registrant

- submitted toxicity data for birds, mammals, freshwater fish, aquatic invertebrates and aquatic plants

.

The assessment also evaluates the potential for picaridin to directly or indirectly affect listed species or modify designated critical habitat. A ssessment endpoints may include direct toxic effects on the survival, reproduction, and growth of l isted entities, as well as indirect effects, such as reduction of the prey base or modification of habitat. In addition, potential modification of critical habitat is assessed by evaluating effects to the primary constituent elements (PCEs), which

are com ponents of the critical habitat areas that provide essential life cycle needs of listed entities.

The most sensitive endpoint for each taxon is used for risk estimation , which in the case of picaridin is from a single study for each taxon

. T his assessm ent, evaluated 5 taxa include

1 The Catabol 301c model is publically available on

- line at: http://oasis

- lmc.org/products/models/environmental

fate

- and

- ecotoxicity/catabol

- 301c.aspx

### Page 10 of 45

freshwater fish

, a freshwater crustacean , birds, an aquatic non

- vascular plant and mammals. Table 4.1 provides a summary of the taxonomic groups

, surrogate species tested , and results of studies to characterize the potential acute ecological effects of Picaridin (no chronic toxicity studies are available)

.

Table 4.1 . Test Species Evaluated for Assessing Potential Ecological Effects of P icaridin and the Associated Acute Toxicity Classification.

Taxonomic Group Tested Speci es

and Study Type Toxicity Endpoint Study MRID and Toxicity Classification

Birds 1 Acute oral No avian oral toxicity data

Bobwhite quail ( Colinus virginianus ) Avian dietary LC 50 > 5000 mg ai/ k g

- diet 44408739 Practically non

- toxic acceptable

Avian re production No data

Mammals Laboratory rat

( Rattus norvegicus ) (acute oral) LD 50 = 2236 mg ai/ kg

- bw Category III 3

Laboratory rat chronic LOAEL > 400 mg/Kg/Day

Insects Honey bee ( Apis mellifera ) No data

Freshwater fish 2 Rainbow trout

( Oncorhynch us mykiss ) LC 50 = 173 mg ai/ L NOAEC = 50 mg ai/L 44408740
pra c tically non

- toxic acceptable

Freshwater invertebrates Waterflea

,

Daphnia magna EC 50 > 103 mg a.i./L 44408741 practically non

- toxic acceptable Estuarine/marine fish No data

Estuarine/marine i nvertebrates No data

Terrestrial plants No data

Aquatic plants and algae Green algae,

Scendesmus subspicatus 72 hour EC 50 = 87.3 mg ai/L NOAEC = 54.8 mg ai/L 44408742 Supplemental

- 72 hour study

1 Birds are considered surrogates for terrestrial

- phase am phibians and reptiles.

2 Freshwater fish are considered surrogates for aquatic

- phase amphibians.

3 Study classification made by Health Effects Division (HED).



## 4.1 Effects to Aquatic Organisms

Technical grade picaridin is classified as practically non

- toxic to fish ( which serve as surrogates for aquatic

- phase amphibians ) and practically non

- toxic to aquatic freshwater invertebrates

. T oxic ity to aquatic algae was observed at concentrations 1000 times above any expected exposure levels

. Toxicity data were not available for evaluation of picaridin chronic exposure to freshwater fish and invertebrates. No toxicity data were available for estuarine/marine fish and invertebrates or for vascular aquatic plants.

### Page 11 of 45



## 4.2 Effects to Terrestrial Organisms
Picaridin is practi cally non toxic to birds on a subacute dietary exposure basis and is practically

non

- toxic to mammals on an acute oral exposure basis. There was no chronic toxicity data were available for birds. The subacute avian dietary LC 50 

### was greater than 5000 mg a. i/kg

- diet

. Picaridin is slightly toxic to mammals on an acute oral exposure basis with a fasting LD 50 

### of 2236 mg ai/Kg to 4743 mg ai/Kg for a non

- fasting male rat. In a 14 week feeding study the subchronic LOAEL was determined to be 1033 mg/Kg/day for l aboratory rats based on decreased b ody weight in males and females and effects to male k idneys including increased weig ht and nephropathy. No developmental toxicity was observed at up to 400 mg/Kg/day in laboratory rats.

No toxicity data were available f or bees, non

- target insects, or terrestrial plants. Given the repellency action of p icaridin , it is likely that many terrestrial invertebrates would be repelled

, and thus, not expose d for significant periods of time.



## 4.3 Degradate toxicity

Although the guide line hydrolysis for picaridin (MRID No. 44408743) indicates that picaridin is stable for up to 30 days, there is evidence that picaridin can degrade in the environment. Extracts from monitoring data in effluent water from a wastewater treatment plant in G ermany indicates that picaridin degrades to the principle degradate picaridin carboxylic acid in the environment (Knepper, 2004). Most other known pipieridine compounds (e.g., paroxetine, methylphenidate, raloxifene, minoxidil, risperidone, and pethidine to name a few) are larger , more complex compounds than picaridin , and some are not racemic mixtures. Therefore, little information is known on the fate and transport characteristics, toxicity, and the amount formed of picaridin carboxylic acid or other d egradates from the picaridin parent material based on literature information related to picaridin or other piperidine compounds (SRC database) 2



### . Given the lack of information on degradates, including their toxicity, any degradates will be presumed to have the same toxicity as the parent , and total toxic residues will assumed to be stable in the environment for exposure estimates

.



## 4.4 ECOTOX Open Literature

Literature identified in the search of the publically available ECOTOX database resulted in one citatio n for Picaridin ( Appendix B ). The cited aquatic toxicity study with an African Tilapia species did not provide endpoints that were more sensitive than the data that was submitted to the Agency. In addition, none of the aquatic data filled existing data gap s (e.g., chronic toxicity to freshwater fish and invertebrates

, acute and chronic toxicity to estuarine/marine fish and invertebrate).

2 Available on

- line: http://www.srcinc.com/what

- we

- do/enviro nmental/scientific

- databases.html

### Page 12 of 45

There were no studies located in ECOTOX for terrestrial wildlife

. One efficacy study evaluating the toxicity of picari din to mites was identified but the data are not toxicologically relevant for this risk assessment.

.



## 5. Problem Formulation

The purpose of problem formulation is to provide the foundation for the environmental fate and ecological risk assessment for the re gistration review risk assessment for the insect repellant

, p ica ridin . The problem formulation sets the objectives for the risk assessment, establishes a risk hypothesis and conceptual model depicting potential risk, and provides a plan for analyzing the data and characterizing the risk associated with the uses of p i caridin (USEPA, 1998 ).



## 5.1 Conclusions from Previous Risk Assessments

EFED has not conducted any ecological risk assessments for p icaridin

. Since p icaridin was registered in 200 0 , i t is a relat ively new pesticide. Therefore, it was not evaluated under the Reregistration program.



## 5.2 Conceptual Model

Given the use and application of picaridin to human subjects and horse skin , the following describes conceivable exposure pathways to non

- target orga nisms in the environment:

 Aquatic Exposure: Washoff of picaridin residues may occur with treated individuals enter ing water bodies as well as due to showering/bathing and laundry cleaning activities

. Therefore, related exposure of non

- target aquatic pla nts and animals including federally

- listed threatened and endangered species may occur.

 Terrestrial Exposure: D irect applications of picaridin to human skin and cl othing, are not expected to result in significant exposure to non

- target terrestrial plants and animals including federally

- listed threatened and endangered species

. Exposure in terrestrial habitats would be limited to human skin, clothing, and shoes, as well as horse skin and hair. Products formulated as lotions or impregnated wipes would be a pplied directly to the human skin. Many other product labels specify recommended spray distances of less than 10 inches from the intended application sites (human skin, clothing, and shoes, as well as horse skin and hair). However, movement off of treated subjects are n ot anticipated for picaridin in the terrestrial environment. Therefore, the amount of picaridin resulting from human or horse application in the terrestrial environment (air, ground, plants, or non

treated animals) is inconsequential.

### Page 13 of 45



## 5.3 An alysis Plan

In order to address the risk hypothesis, the potential for adverse effects on the environment is estimated. The use, environmental fate, and ecological effects of picaridin are characterized and integrated to assess the risks. This is accomp lished using a risk quotient (ratio of exposure concentration to effects concentration) approach. Although risk is often defined as the likelihood and magnitude of adverse ecological effects, the risk quotient (RQ)

- based approach does not provide a quanti tative estimate of likelihood and/or magnitude of an adverse effect. T he likelihood of effects to individual organisms from particular uses of picaridin has been estimated using the actual estimated risk quotient value s

.

5.3.1 Residues of Concern

The parent compound, picaridin , is the toxicant that will be assessed. Toxicity of picaridin isomers and degradates , including picaridin carboxylic acid, will be assumed to be equivalent to parent compound in the absence of data to suggest otherwise.

5.3.2 Evaluation o f Multiple Active Ingredients, Mixtures and Formulated Products

The Agency does not routinely include in its risk assessments an evaluation of mixtures of active ingredients, either those mixtures of multiple active ingredients in product formulations or those in the applicator’s tank. In the case of the product formulations of active ingredients (that is, a registered product containing more than one active ingredient), each active ingredient is subject to an individual risk assessment for regulatory dec ision regarding the active ingredient on a particular use site. If effects data are available for a formulated product containing more than one active ingredient, they may be used qualitatively or quantitatively.

5.3.3 Measures of Exposure

The ecosystems p otentially at risk are often extensive in scope; therefore, it may not be possible to identify specific ecosystems during the development of a nation

- wide ecological risk
assessment.

Aquatic ecosystems potentially at risk from picaridin exposure include water bodies adjacent to, or downstream from, the water bodies that were entered by treated humans or horses

. In order to estimate risks of picaridin exposures in aquatic environments, all exposure modeling and resulting risk conclusions will be based on maximum application rates and methods. Measures of aquatic exposure are typically based on models that predict estimated environmental concentrations (EECs) of picaridin such the Pesticide Root Zone Model coupled with the Exposure Analysis Modeling Syste m (PRZM/EXAMS). However, b ecause of the limited application methods (directly to human skin, clothing , shoes, and horse skin), the typical models used for exposure estimation (e.g., PRZM/EXAMS) will not be used in this assessment.

Environmental exposure concentrations are calculated assum ing that picaridin reaches surface

### Page 14 of 45

water directly via treated human subjects enter ing the water body, and that t he entire application of picaridin is p resumed to wash off and remain in the water column. Water concentrat ions in the standard pond will be ca lculated under the assumption that picaridin is released directly into the pond from 10 treated adults, 100 treated adults, or 10 treated horses. Another scenario where 50 cans of the product are directly released into the pond will be evaluated

. Application of the equivalent of 50 cans of product represents a highly unlikely, very conservative aquatic exposure scenario, as it is not expected that such a large number of treated individuals would enter a single 1

– hectare water body within a 24 hr period. The scenario is presented as a convenient measure to evaluate the plausibility of exposure levels approaching those that may cause concern for aquatic organisms.

Because of the application method and limited scope of use sites for picaridin, terrestrial ecosystems potentially at risk could include the area in which treatment (application to human or horse) occurred. Exposure to non

- target terrestrial organisms and plants is presumed negligible ( Se ction 5.2 ) and will no t be estimated.

5.3.4 Measures of Effect

Measures of effect are obtained from a suite of registrant

- submitted guideline studies that were conducted with a limited number of surrogate test species ( Table 5

. 1 )

. Toxicity data generated using surrogate test spe cies, which are intended to be representative of broad taxonomic groups, are used to infer potential effects on a variety of species (receptors) included under these broader taxonomic groupings. Birds represent surrogates for terrestrial

- phase amphibians and reptiles, and freshwater fish represent surrogates for aquatic

- phase amphibians. No additional non

- target ecotoxicity data on picaridin were located, based on a recent query of the open literature in the publically available version of the ECOTOX datab ase ( http://cfpub.epa.gov/ecotox/ ).

Table 5

. 2 lists the measures of environmental exposure and ecological effects used to assess the potential risks of picar i din to non

- target organisms. Assessment endpoints r epresent the actual environmental value that is to be protected, defined by an ecological entity (species, community, or other entity) and its attribute or characteristics (USEPA, 1998). The attributes for each of these entities may include grow th, surviv al, and reproduction

.

Table 5 .1. Measures of Exposure and Effect Used in Assessing Potential Risks Associated with the Registered Uses of Picaridin.

Assessment Endpoint Surrogate Species and Measures of Ecological Effect 1 Measures of Exposure

Aquatic A nimals (Freshwater fish and invertebrates) 2 Survival Lowest tested LC 50 or EC 50 (acute toxicity test) E stimated aquatic concentrations after treated individuals entered water body
Reproduction and Growth No data Not calculated as no acute LOC exceedances and no chronic toxicity data available Aquatic Animals (Estuarine/marine fish and invertebrates) 2 Survival No data Presumed concentrations in water equal or less than those estimated for small freshwater pond

### Page 15 of 45

Table 5 .1. Measures of Exposure and Effect Used in Assessing Potential Risks Associated with the Registered Uses of Picaridin.

Assessment Endpoint Surrogate Species and Measures of Ecological Effect 1 Measures of Exposure

Reproduction and Growth No data Not calcul ated as there were no acute LOC exceedances and no chronic toxicity data available

Aquatic plants Growth EC50 for Growth effects with Freshwater Algae No vascular plant data available E stimated aquatic concentrations after treated individuals entered
wate r body

Birds 3 Survival Lowest acute L C 50 ( 5 day dietary exposure ) No L D 50 oral data available

Not calculated as significant
exposure is not expected Reproduction and Growth No data

Mammals Survival Lowest oral acute LD 50

Reproduction and Growth Lo west NOAEC

reproductive effects (2

- generation reproduction test)

Insects Survival No data Not calculated as significant
exposure is not expected
Terrestrial plants Survival and growth No data Not calculated as significant
exposure is not expected

1 Th e most sensitive species tested within taxonomic groups is used for screening

- level risk assessments.

2 Freshwater fish are considered surrogates for aquatic

- phase amphibians.

3 Birds are considered surrogates for terrestrial

- phase amphibians and reptiles.



### 5.3.5 Integration of Exposure and Effects

Exposure and toxicity data are integrated in order to evaluate the risks of adverse ecological effects

on non

- target species. For the screening

- level risk assessment of picaridin , the deterministic risk quotient (RQ ) method is used to compare estimated exposure concentrations with measured toxicity values. The RQ method involves dividing point estimates of environmental concentrations by acute and chronic toxicity values. The resulting unitless RQs are then compare d to the Agency’s Levels of Concern (LOC) ( Table 5

. 2 ). These criteria are used to indicate when applications of picaridin

, as directed on the proposed labels, have the potential to cause adverse effects to listed and non

- listed non

- target organisms.

Table 5 .2. Agency Acute Risk Quotient (RQ) Metrics and Levels of Concern (LOC) for Aquatic Animals (fish and invertebrates)

RISK CLASS RISK DESCRIPTION RQ LOC

Acute Potential for effects to non

- listed animals from acute

exposures Peak EEC/LC 50 1 0.5

### Page 16 of 45

Table 5 .2. Agency Acute Risk Quotient (RQ) Metrics and Levels of Concern (LOC) for Aquatic Animals (fish and invertebrates)

RISK CLASS RISK DESCRIPTION RQ LOC

Acute Re stricted Use Potential for effects to animals from acute exposures

Risks may be mitigated through restricted use classification Peak EEC/LC 50 1 0.1

Acute Listed Species Listed species may be potentially affected by acute

exposures Peak EEC/LC 50 1 0.05

1 LC 50 or EC 50
.



## 5.4 Endangered Species Assessment

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the Agency evaluates risks to Federally

- listed threatened and/or endangered (listed) species from registered uses of picaridin

. The assessment of effects associated with the registration of picaridin is based on an action area. The action area is considered to be the area directly or indirectly affected by the federal action, as indicated by the exceedance of Agency LOCs used to evaluate direct or indirect effects. The action

area is defined using the results of the risk assessment to establish boundaries for that action area with the understanding that exposures below the Agency’s defined LOCs constitute a no

- effect threshold . For the purposes of this assessment, attention will be focused on the footprint of the action ( i.e ., the area where picardin application occurs), plus all areas where offsite transport may result in potential exposure that exceeds the Agency’s LOCs. Sp ecific measures of ecological effect that define the action area for listed species include any direct and indirect effects and/or potential modification of its critical habitat, including reduction in survival, growth, and reproduction as well as the full suite of sub

- lethal effects available in the effects literature. Therefore, the action area extends to a point where environmental exposures are below any measured lethal or sub

- lethal effect threshold for any biological entity at the whole organism,
orga n, tissue, and/or cellular level of organization. In situations where it is not possible to determine the threshold for an observed effect, the action area is not spatially limited and is assumed to be the entire United States.



## 5.5 Endocrine Disruptor Scre ening 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 carcinogenici ty, 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

### Page 17 of 45

taxonom ic groups. 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 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 potentia l 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

- re lated 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 chemicals identified for EDSP screening was published on June 14, 2013 3 

### and includes some pesticides sc heduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

P icaridin is not among the group of 58 pesticide active ingredients receiving EDSP test orders. F or information on the status of the orders issued under the EDSP for each chemical, please visit our website at http://www.epa.gov/endo/ and click on the "Status of EDSP Orders/DCIs" in the Highlights Box. Additional information on the EDSP, including the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, can also be found at this website.



## 6. Exposure Analysis

6.1 Estimated Surface Water Concentrations

In order to estimate risks of picaridin exposures in aqu atic environments, all exposure modeling and resulting risk conclusions will be based on maximum application rates and methods. Measures of aquatic exposure are typically based on models that predict estimated environmental concentrations (EECs) of picarid in such the Pesticide Root Zone Model coupled with the Exposure Analysis Modeling System (PRZM/EXAMS). However, b ecause use is restricted to direct application to human skin, clothing, shoes, and horse skin, the typical models (e.g., PRZM/EXAMS) used for e xposure estimation will not be used in this assessment.

Aquatic exposure could be expected via two routes: (1) washoff from treated skin and clothing when people enter water bodies and (2) washoff from treated skin and clothing when people bathe

3 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of chemicals.

### Page 18 of 45

or laund er clothing. However, only the aquatic exposure scenario resulting from treated humans and horses swimming in water bodies ( first scenario above ) are expected to account for peak and high

- end EECs and would be protective of any pot ential “down

- the

- drain” t ype of exposure scenario associated with laundering or showering

. Therefore, only the direct application scenarios will be evaluated and presented in this assessment.

E nd

- use product s for humans and horses containing t he highest quantity of picaridin i n single sale container s will be evaluated for potential aquatic exposure. In general, picaridin products such as ready

- to

- use solutions, pumps, and aerosol sprays are sold in cans containing up to 6 fl. oz. of product containing up to 20% picaridin, or t he equivalent of 1.2 fl. oz. or 32,25 5 mg of picaridin
per can 4 

### . In addition, fifty 6 fl. oz. can s of repellant contains the same amount of picaridin as 5,940 picaridin towelette s impregnated with picaridin ( 330 pack s of the product containing 18 towelett es )

.

The standard scenario s used for ecological pesticide assessments assume application to a 10

- hectare agricultural field that drains into an adjacent 1

- hectare water body that is 2 meters deep (20,000 m 3 

### volume equivalent to 20,000,000 L ) with no outle t. Upper

- bound p icaridin water concentrations in the standard pond will be calculated assuming all of picaridin directly washes off into the water body given four scenarios. Scenario 1 assumes that 10 treated adults enter the pond. Scenario 2 assumes th at 100 treated adults enter the pond. Scenario 3 assumes that 10 treated horses enter the water body on a single day. Scenario 4 assumes that t he entire contents of 50 cans or 330 towelette packs of the product (both possessing an equivalent of 32,25 5 mg of picaridin) are released to the pond. Application of the equivalent to 50 cans or 330 towelette packs of product directly to the water body represents a highly unlikely, very conservative aquatic exposure scenario, as it is not expected that such a lar ge number of treated individuals would enter a single 1

– hectare water body within a 24 hr period. Picaridin application to ten horses also represents a high exposure scenario for the horse use pattern.

The Standard Operating Procedures for Residential Pes ticide Exposure Assessment developed by the Health Effects Division (HED) p rovide methods for assessment for pesticide repellants (citation: http://www.epa.gov/pe sticides/science/residential

- exposure

- sop.html#sops )

. E xposure assessment methods in this document include scenario s reflecting individuals who purchase pesticides and complete their own applications

, such as adult and child application rate calculations for insect repellants. Of the different available application methods and concentrations of picaridin in the individual products, pump sprays and aerosol sprays provide the highest application rates per individual. HED ’ s methodology determines an applied dose (mg a.i./kg

- day) as well as an absorbed dose (mg a.i./ kg

- day); however for the purposes of this aquatic exposure estimation, the applied dose will be used and converted to a total daily dose per individual using an average adult body weight of 80 kg:

D = AR F 

### * F AI 

### * ET * AppF * SA/BW * F Body 

### * BW

where : D = dose (mg ai /individual

- day);

4 32,255 mg of picaridin per can = 6 fl oz. of product/can x 20% picaridin (% a.i.) x 29.57 fl oz./mL (conversion factor) x 0.909 g/mL (density of picaridin) x 1,000 mg/g (conversion factor)

### Page 19 of 45

AR F 

### = formulation

- specific application rate (mg product/cm 2 

### skin); F AI 

### = product

- specific fraction of active ingredient (mg ai/mg product); ET = exposure time (hour s/day); AppF = application frequency (applications/hour); SA/BW = total body surface area to body weight ratio (cm 2 

### skin /kg); F Body 

### = fraction of body exposed (fraction exposed/application); BW = 80 kilograms /individual

. For adult human applications, AR F 

### , ET, AppF, SA/BW, F Body 

### , and B W were determined using default values from HED ’ s SOP. For horses, the SA/BW and BW values were 100 cm 2 

### /kg and 500 kg, respectively ( citation: http://www.dpi.vic.gov.au/agriculture/animals

- and

livestock/horses/management/feed

- budgets

- for

- horses )

. The contribution to the exposure created from individual treated adult human and horse subjects entering the wate r body in scenarios 1, 2, or 3 described above is shown in Table 6.1 . The total bulk upper

- bound acute estimated exposure concentration s (EEC s ) in water bodies resulting from picaridin treatments and resulting exposure described in scenarios 1, 2, 3, and 4 described above

are shown in Table 6.2

.

Table 6.1

. Calculations for determining mg a.i./individual/day for scenarios 1 , 2 or 3

.

Applied Subject Amount

of ai in product (mg ai/mg product) Formulation

specific AR (mg product/cm 2 skin) Fraction

Body Exp osed Exposure

Duration (days) Application

Frequency (#/hour) SA to BW

Ratio (cm 2 /kg) Exposure

(mg a.i. /kg

day) a Exposure

(mg a.i. / individual/ day) b

Human 0. 20 1.10 0.75 3.7 0.25 280 42.7 3,418.8

H orse 100 15.3 7,631.3

a Exposure calculated by m ultiplying the values in the preceding six columns (see Standard Operating Procedures for Residential Pesticide Exposure Assessment at http://www.epa.gov/pesticide s/science/residential

- exposure

sop.html#sops for details).

b Individual exposure calculated by multiplying estimated body weight (80 kg for adult humans and 500 kg for horses) by exposure (mg a.i./kg

- day) from the preceding column.



### Table 6.2

. Upper

- bo und a quatic exposure EECs for picaridin applications (mg a.i./L)

.

Release Scenario and Description Exposure (mg a.i. / individual/ day) Total Picaridin Mass

Washoff (mg) Bulk Acute

Picaridin Pond EEC (mg /L ) a
Scenario 1

- 10 treated adults to water body 3 ,418.8 34,188 0.0017

Scenario 2

- 100 treated adults to water body 341,880 0.017 Scenario 3

- 10 treated horses to water body b 7,631.3 b 76 ,313 b 0.00 38 Scenario 4

- 50 cans product or 330 packs of

towelettes impregnated with picaridin released to water body ,c ,d N/A 1,612, 748 c ,d 0.081

a Pond volume of 20,000,000 L.

b Calculated using same approach as for adult humans except surface area to body weight ratio was 1 00 cm 2 /kg and body weight was 500 kg ( http://www.dpi.vic.gov.au/agriculture/animals

- and

- livestock/horses/management/feed

budgets

- for

- horses 

### ).

### Page 20 of 45 c Calculated based on 50, 6 fl oz. cans of product filled with end use product composed o f 20% picaridin [ 6 fl oz. of product

/can x 20% picaridin (% a.i.) x 29.57 fl oz./mL (conversion factor) x 0.909 g/mL (density of picaridin) x 1,000 mg/g (conversion factor) x 50 cans] are applied directly to water body

. d 6.6 packs of towelettes possess eq uivalent amount of picaridin contained within one can of product. Therefore, 330 packs of towelettes possess same amount of picaridin contained amongst 50 cans of product.

e Maximum EEC shown in bold face.



## 6.2 Monitoring Data for Picaridin

Limited informa tion regarding environmental monitoring data are a vailable for picaridin. However, in one study, picaridin was detected in influent waters to a wastewater treatment plant in Germany at conce ntrations between 0.6

- 1.4  g/L (Knepper, 2004). The Knepper paper noted the consistent decline in DEET concentrations observed in surface waters over a 5 year period coinciding when picaridin appeared on the local market as an alternative to DEET.

The sampling interval and durati on in the study is not specified. In effluent waters, picaridin was not detected. However, the carboxylic acid degradate of picaridin was detected in the effluent waters (Knepper, 2004 ). The levels at which picaridin carboxylic acid was detected at was not quantified. The upper

- bound EEC of 81  g/L calculated from Table 6.2 of Section 6.1 is higher than picaridin concentrations detected in the influent wastewater treatment plant waters by a magnitude of approximately 58X.



## 6.3 Terrestrial Exposure Analysis

Exposure to non

- target terrestrial organis ms and plants is presumed negligible based on use patterns ( Section 5 .2 ) and will not be estimated.



## 7. Risk Characterization

7.1 Risk Estimation

Toxicity data and exposure estimates are used to evaluate the potential for adverse ecological effects on non

- target species. This assessment for picaridin relies on the deterministic RQ method to provide a metric of potential risks. The RQ provides a comparison of exposure estimates to toxicity endpoints ( i.e. , the estimated exposure concentrations are divided by acu te toxicity values). The resulting unitless RQs are compared to the Agency’s LOCs, as shown in Table 4.1

. LOCs are used by the Agency to indicate when the use of a pesticide, as directed by the label, has the potential to cause adverse effects to non

- tar get organisms.

7.1.1 Aquatic Organisms

The screening

- level aquatic EECs based on the application rates for highest concentration products for human use and the only product registered for horse use. The exposure estimates

, represent ing human or ho rse wash off concentrations in a 20 million liter pond , and aquatic toxicity data were

### Page 21 of 45

used to calculate acute RQs ( Table 7 .1 ). The expected concentrations of picaridin in the aquatic environment are several orders of magnitude lower than the observed aqu atic LC 50 

### and EC 50 

### s determined for p icaridin , and thus the potential for adverse risks is low.

Table 7

. 1 Upper

- bound Acute a quatic exposure RQs for picaridin applications (mg a.i./L)

.

Release Scenario and Description Exposure (mg a.i. / individual/ da y) Total

Picaridin Mass Washoff (mg) Bulk

Acute Picaridin Pond EEC (mg /L ) a RQ for

Freshwater Fish 2 RQ for

Freshwater Invertebrate RQ for

Aquatic Plants

Scenario 1

- 10 treated adults to water body 3,418.8 34,188 0.0017 < 0.001 < 0.001 < 0.001

Scenario 2

- 100 treated adults to water body 341,880 0.017 < 0.001 < 0.001 < 0.001

Scenario 3

- 10 treated horses to water body 7,631.3 b 76,313 b 0.0038 < 0.001 < 0.001 < 0.001

Scenario 4

– 50 cans product or 330 packs of towelettes impregnated with picaridin rel eased to water body , N/A 1,612,748 c,d 0.081 < 0.001 < 0.001 <0.001

a EECs Based on a Pond volume of 20,000,000 L.

b LC 50 for fish = 173 mg a.i/L . EC50 for FW Invertebrate > 103 mg a.i/L . EC 50 for FW Algae = 83 mg a.i/L

c Maximum EEC shown in bold.



### 7.1.2 Terrestrial Organisms

No significant exposure to terrestrial organisms is predicted based current use patterns for p icaridin ( localized spray ) and the active ingredient is determined to be practically non

- toxic to birds and only slightly toxic t o mammals. Therefore, risk to terrestrial organisms is not estimated

.

7.1.2 Incident Database Review

A review of the following databases was completed in March, 2014 :

 Ecological Incident Information System (EIIS ),

 ‘Aggregate Incident Reports’ databa se ,

 Avian Incident Monitoring System (AIMS

, http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims )

 Contaminant Exposure and Effects

– Terrestrial Vertebrate (CEE

- TV, http://www.pwrc.usgs.gov/contaminants

- online/pages/CEETV/CEETVintro.htm ).

No inc idents for picaridin were identified in the EIIS, AIMS , the OPP Incident Data System (IDS) or the CEE

- TV databases

.

### Page 22 of 45



## 7.2 Risk Description

7.2.1 Exposure and Risk to Aquatic Organisms

The results of risk estimation indicate that registered uses of picaridin will n ot result in acute RQs that exceed the LOC for freshwater fish and invertebrates. Chronic RQs for freshwater organisms were not calculated; however, given the large margin of safety observed for acute effects based on the most conservative exposure scenar io , it is unlikely that chronic RQs would approach concern levels. Additionally, there are no acute or chronic estuarine/marine data for fish and invertebrates with which to estimate RQs, however risk is presumed to be below the level of concern based on low toxicity to freshwater taxa and low exposure in the water column.

RQs were calculated for non

- vascular aquatic plants using the limited toxicity data that were available. RQs were estimated to be lower than the non

- listed LOC for non

- vascular aquatic plants

. Toxicity data are not available for vascular aquatic plants but risk is presumed to be below the level of concern based on low toxicity to aquatic non

- vascular plants and low exposure in the water column. Also, there are no reported incidents fo r aquatic organisms or plants

.

7.2.2 Risks to Terrestrial Organisms

Exposure in terrestrial habitats would be limited to human skin, clothing, and shoes, as well as horse skin and hair. Products formulated as lotions or impregnated wipes would be applied dir ectly to the human skin. Many other product labels specify recommended spray distances of less than 10 inches from the intended application sites (human skin, clothing, and shoes, as well as horse skin and hair). Any movement away from the site of applicat ion represents potential exposure pathways for a broad range of biological receptors of concern (non

- target terrestrial animals and plants) and the potential attribute changes, i.e. , effects such as reduced survival, growth and reproduction, in the recepto rs due to picaridin exposure. However, t he amount of picaridin resulting from human or horse application in the terrestrial environment (air, ground, plants, or

non

- treated animals) is inconsequential. As there is no complete exposure pathway to result in substantive exposure of non

- target terrestrial organisms under the currently registered uses

, EFED has presumed risk is discountable to terrestrial organisms

.



## 7.3 Uncertainties , Limitations, and Data Gaps

With only one acceptable hydrolysis study submitted to the Agency , the re are many data gaps for fate and transport parameters . However, the available open literature and monitoring data suggest picaridin does exist in aquatic environments with low concentrations. Furthermore, it has been demonstrated tha t picaridin can degrade to picaridin carboxylic acid to some extent in the environment (Knepper, 2004). The rate at which picaridin degrades to the carboxylic acid and the amount of picaridin carboxylic acid is not known. However, t he calculated upper

- bo und exposure based on wash off from treated humans and horses into a pond and the monitoring data suggest that potential aquatic exposures are very low, several orders of magnitude less than levels of

concern. As a result, chronic exposure is not expected given the very low exposure occurring from

a one

- time short

- term release into water. In addition, picaridin would have to be greater than three

### Page 23 of 45

orders of magnitude more toxic on a chronic basis than acute in order to exceed the chronic LOC for all aquati c taxa. This is assuming the acute EEC is equivalent to the chronic EEC. This assumption does not consider the decrease of exposure overtime resulting from the degradation of total toxic residues or any mixing that would occur to dilute the picaridin con centration overtime. C hronic exposure resulting in adverse effects would also be highly unlikely since rep etitive

sce n arios where picaridin washoff occurs from masses of people and horses in water bodies is not expected to occur frequently over a localized area. However, it should be noted that although chronic exposure is anticipated to be small, its full extent occurring in water bodies where picaridin is released is unknown based on the information currently available on the degradation of picaridin in the environment.

Few ecotoxicity studies have been submitted to the Agency, and th ere are many data gaps for the effects data . However, under the currently registered use patterns, EFED has concluded (1) low likelihood of risk to aquatic organism s (2) lo w likelihood of risk to terrestrial organisms due to the lack of an exposure pathway

. Unless the use patterns of picaridin change through proposed registrations of new labels, EFED determines that additional data would not have substantial added value to the overall risk
assessment.

. 

## 8. Federally Threatened and Endangered (Listed) Species Concerns

Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all federal agencies to consult with the National Marine Fisheries Service (NMFS) for marine and anadromous listed species, and/or the United States Fish and Wildlife Service (USFWS) for listed wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species or their designated critical habitat

. The f ederal action addressed herein is the proposed registration renewal of picaridin for human and horse use and it is expected that the use could occur nationwide.

For a more detailed general description of the Endangered Species assessment process and the

v arious components and assumptions of this process see Appendix E at the end of this document.

For the uses of picaridin, risk from acute exposure is not expected for any listed non

- target animals or plants ( Table 8.1 ). Additionally, the Agency has determi ned that there will be no habitat modification of any designated critical habitat for listed species from the current registered uses of picaridin. Inference regarding aquatic organisms and plants are based on the risk conclusions that registered uses of picaridin will not result in LOC exceedances for acute risk to fish and invertebrates. Based on expected EECs and limited acute plant data on algal species, EFED presumed direct risks were lower than concern levels to aquatic plants. In addition, there h ave been no reported incidents for picaridin use to non

- target plants, wildlife or aquatic life. No chronic data were available to allow for chronic RQ calculations. However, given the large margin of safety observed for acute effects based on the most conservative exposure scenario, chronic RQs are unlikely to exceed concern levels. Conclusions regarding terrestrial organisms and plants are based on the lack of a complete exposure pathway. Exposure in terrestrial habitats would be limited to human ski n, clothing, and shoes, as well as horse skin and hair. Products formulated as

### Page 24 of 45

lotions or impregnated wipes would be applied directly to the human skin. Many other product labels specify recommended spray distances of less than 10 inches from the intended application sites (human skin, clothing, and shoes, as well as horse skin and hair). Exposure to listed species is not expected because they would not likely come in close contact with humans or domestic horses ( i.e., the registered use sites).

Table 8 .1 . Potential Effects to Federally Listed Taxa Associated with Direct or Indirect Effects from the Currently Registered Uses of Picaridin

.

Listed Taxon Direct Effects Indirect Effects
Terrestrial and semi

- aquatic plants

- monocots



### No No Terrestrial and s emi

- aquatic plants

- dicots

Birds Terrestrial

- phase amphibians and reptiles

Mammals Terrestrial invertebrates Aquatic nonvascular plants Aquatic vascular plants Freshwater fish Aquatic

- phase amphibians Freshwater invertebrates Marine/estuarine fish Marine/estuarine invertebrates

### Page 25 of 45



## 9. References

Amer, A.; Mehlhorn, H. 2006. The sensilla of Aedes and Anopheles mosquitoes and their importance in re pellency. Parasitol. Res. 99, 491

- 499.

Klun, J. A.; Khrimian, A.; Debboun, M

. 2006. Repellent and Deterrent Effects of SS220, Picaridin, and DEET Suppress Human Blood Feeding by Aedes aegypti, Anopheles stephensi, and Phlebotomus p apatasi. J. Med. Entomol. 43 (1), 34

- 39.

Knepper, T.P, 2004 . Analysis and mass spectrometric charac terization of the insect repellent Bayrepel and its main metabolite Bayrepel

- acid. J. Chromatogr. A, 1046, 159

- 166.

Licciardi, S.; Herve, J. P.; Darriet, F.; Hougard, J.

- M.; Corbel, V. Lethal and behavioral effects of three synthetic repellents (DEET, IR3 535 and KBR 3023) on Aedes aegypti mosquitoes in laboratory assays. Med. Vet. Entomol. 2006, 20, 288

- 293.

Moore, S. J.; Debboun, M. Insect Repellents: Principles, Methods, and Uses

- History of Insect Repellents; Debboun, M.; Frances, S. P.; Strickman, D.

, 2007. Eds .; CRC Press: Boca Raton, pp 3

- 29.

USEPA. 1998

. Guidelines for Ecological Risk Assessment . United States Environmental Protection Agency (USEPA). Risk Assessment Forum. Office of Research and Development. Available at http://cfpub.epa.gov/nce a/cfm/recordisplay.cfm?deid=12460 (Accessed June 19, 2009).

USEPA. 2005. Pesticide Fact Sheet for Picaridin . United States Environmental Protection Agency (USEPA). Office of Pesticide Programs. Available on

- line at http://www.epa.gov/opp00001/chem_search/reg_actions/registration/fs_PC

- 070705_01

- May

05.pdf (Accessed February 18, 2014).

U S EPA 2012. Standard Operating Procedures for Residential Pesticide Exposure Assessment. U.S. Environmental Protection Agency, Office of Pollution Prevention and Toxics, Office of Pesticide Programs, Health Effects Division. Washington DC. http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

USFWS/NMFS/NOAA.2004. 50 CFR Part 402. Joint Counterpart Endangered Species Act Section 7 Consultation Regulations; Final Rule. Federal Register Volume 69. Number 20. Pages 47731

- 47762. August 5, 2004.

WHO , 2004. WHO specifications and evaluations for public health pesticides. Icaridin. Geneva, Switzerland: World Health Organization. http:// www.who.int/whopes/quality/en/Icaridin_spec_eval_Oct_2004.pdf

### Page 26 of 45



## Appendix A : Environmental Fate and Ecotoxicity Data Requirement Tables

T able A

- 1

. Available environm ental fate data for picaridin and remaining data gaps.
158 Guide line (OPPTS) Description MRID Classification Data Gap?

835.1230 (163

- 1) Leaching No data N/A No*

835.1240 (163

- 1) Adsorption/desorption No data N/A No*

835.1410 (163

- 2) Laboratory volatility No data N/A No*

835.2120 (161

- 1) Hydrolysis MRID 4440874 3 Acceptable No

835.2240 (161

- 2) Photodegradation in water No data N/A No*

835.2370 (161

- 4) Photodegradation in air No data N/A No*

835.2410 (161

- 3) Photodegradation on soil No data N/A No*

835.4100 (162

- 1) Aerobic soil metabolism No data N/A No*

8 35.4200 (162

- 2) Anaerobic soil metabolism No data N/A No*

835.4300 (162

- 4) Aerobic aquatic metabolism No data N/A No*

835.4400 (162

- 3) Anaerobic aquatic

metabolism No data N/A No*

835.6100 (164

- 1) Terrestrial field dissipation No data N/A No*

835.62 00 (164

- 2) Aquatic field dissipation No data N/A No*

835

- 6300 (164

- 3) Forestry field dissipation No data N/A No*

850.1730 (165

- 4) Fish bioconcentration factor No data N/A No*

NGS Drinking water treatment No data N/A No*

* Not identified as a data gap u nder currently registered uses. Proposal of new uses may change the data requirements.

N/A means not applicable.

### Page 27 of 45

Table A

- 2

. Available ecological effects data for terrestrial animals e xposed to technical picaridin and remainin g data gaps.

158 Guideline (OPPTS) Description MRID/ Accession Classification Data Gap? Comments

850.2100 (71

- 1) Avian oral toxicity No data N/A No

Avian dietary study was conducted as a limit test with no effects at 5000 ppm in diet

. 850.22 00 (71

- 2) Avian dietary toxicity 44408739 Acceptable No*

850.2300 (71

- 4) Avian reproduction No data N/A No*

850.3020 (141

- 1) Honeybee acute

contact toxicity No data N/A No*

850.3040 (141

- 5) Field testing for

pollinators No data

N/A No*

* Not id entified as a data gap under currently registered uses. Proposal of new uses may change the data requirements.

N/A means not applicable.

Table A

- 3

. Available ecological effects data for aquatic animals exposed to technical pica ridin and remaining data gaps.
Guideline Description MRID/ Accession Classification Data Gap?

850.1075 (72

- 1) Freshwater fish

–

acute toxicity 44408740 Acceptable No

850.1075 (72

- 3) Saltwater fish

–

acute toxicity No data N/A No*

850.1010 (72

- 2) Freshwater invertebrates

–

acute toxicity 44408741 Acceptable No

850.1025 s850.1035 (72

- 3) Saltwater invertebrates

–

acute toxicity No data N/A No*

850.1300 (72

- 4) Freshwater invertebrate

–

life cycle test No data N/A No*

850.1350 (72

- 4) Saltwate r invertebrates

–

life cycle test No data N/A No*

850.1400 (72

- 4) Freshwater fish

–

early life stage test No data N/A No*

850.1400 (72

- 4) Saltwater fish

–

early life stage test No data N/A No*

850.1500 (72

- 5) Fish

–

life cycle test No data N/A N o*

* Not identified as a data gap under currently registered uses. Proposal of new uses may change the data requirements.

N/A means not applicable.

### Page 28 of 45

Table A

- 4

. Available ecological effects data for plants exposed to picaridin and remaining data gaps.

Guideline Description MRID Classification Data Gap? Comments

850.4100 (122

- 1) Terrestrial plant toxicity:

tier 1 seedling emergence No data N/A No*

850.4225 (123

- 1) Terrestrial plant toxicity:

t ier 2 seedling emergence No data N/A No*

850.4150 (122

- 1) Terrestrial p lant toxicity :

t ier I vegetative vigor No data N/A No*

850.4150 (123

- 1) Terrestrial plant toxicity:

t ier 2 vegetative vigor No data N/A No*

850.4400 (123

- 2) Aquatic plant g rowth:

algae 44408742 Supplement al No* This was a 72 hour
exposure
850.4400 (123

- 2) Aquatic plant g rowth:

vascular plants No data N/A No*

* Not identified as a data gap under currently registered uses. Proposal of new uses may change the data requirement s.

N/A means not applicable

.



## 850.2200 Avian Dietary Toxicity

MRID Citation Reference

44408739 Schmuck, R. (1997) Five Day Dietary Toxicity of KBR 3023 on Bobwhite Quail (Colinus

virginianus): Lab Project Number: 107844: E 295 1154

- 7: SXR/VB 58. Unpublished study
prepa red by Bayer Ag. 38 p.



## 850.1075 Acute Toxicity to Freshwater Fish

MRID Citation Reference

44408740 Dorgerloh, M. (1996) KBR 3023 Technical

-- Acute Toxicity (96 Hours) to Rainbow Trout

(Oncorhynchus mykiss) in a Static Test: Lab Project Number: E 2501093

- 0: 107845: DOM 96024. Unpublished study prepared by Bayer Ag. 48 p.



## 850.1010 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

44408741 Heimbach, F. (1996) Acute Toxicity of KBR 3023 Technical to Waterfleas (Daphni a magna):

Lab Project Number: 107690: E 320 1103

- 0: HBF/DM 162. Unpublished study prepared by Bayer Ag. 40 p.

### Page 29 of 45



## 850.4400 Acute Toxicity to Non

- vascular Aquatic Plant

MRID Citation Reference

44408742 Anderson, J. (1996) Influence of KBR 3023 Tec hnical on the Growth of the Green

Alga, Scenedesmus subspicatus: Lab Project Number: 107689: E 323 1072

- 8: AJO/146496. Unpublished study prepared by Bayer Ag. 35 p.



## 835 Hydrolysis

44408743 2075607

2075608 Hellpointner, E. (1996) Hydrolysis of (carbon 14) KBR 3023 in Sterile aqueous

Buffers: Lab Project Number: 107961: M 111 0795 4: HPO

- 138. Unpublished study prepared by Bayer Ag. 34 p.

### Page 30 of 45



## Appendix B : Publically Available Data Table from EPA’s ECOTOX Database

Only a single articl e regarding toxicity of picaridin was located in ECOTOX database . It shows effect levels for a species of African Tilapia to be very low. Articles on terrestrial organism effects were not found.

Table B

- 1. Aquatic Ecotoxicity references provided in the p ublically available ECOTOX

CAS Number Species tested Endpoint Conc 1 Mean (ug/L) Units

(ug/L) Reference

Number Author Title Source /
year

134623 Mozambique

Tilapia , Oreochromis mossambicus NR 120000 ug/L 3073 Mathai,A.T., K.S. Pillai, and P.B. Deshmukh A cute Toxicity of Picaridin

to a Freshwater Fish, Tilapia mossambica: Effect on Tissue Glutathione Levels J. Environ. Biol.10(2): 87

- 91

, 1989Page 31 of 45



## Appendix C. Pending and Active Registrations For

Ingredient 070705 / 119515

- 38

- 7 / Picaridin

Registration # Registration Name Company # Co mpany Name Current Status % of

Active Ingredient

121

- 89 CUTTER INSECT

REPELLENT 7K 121 SPECTRUM, A DIV OF UNITED INDUSTRIES CORP Active

-

Conditionally Registered (15

- Dec

2004) 7

121

- 90 CUTTER INSECT

REPELLENT 5KT 121 SPECTRUM, A DIV OF UNITED INDUSTRIES CORP Active

-

Conditionally Registered (16

- Dec

2004) 5.75

121

- 91 CUTTER INSECT

REPELLENT 15KP 121 SPECTRUM, A DIV OF UNITED INDUSTRIES CORP Active

-

Conditionally Registered (20

- Oct

2005) 15

121

- 92 CUTTER INSECT

REPELLENT 15KA 121 SPECTRUM, A DIV OF UNITED INDUSTRIES CORP Active

-

Conditionally Registered (03

- Nov

2005) 15

121

- 93 CUTTER INSECT

REPELLENT 12KT 121 SPECTRUM, A DIV OF UNITED INDUSTRIES CORP Active

-

Conditionally Registered (03

- Nov

2005) 12

121

- 94 CUTTER INSECT

REPELLENT 10KP 121 SPECTRUM, A DIV OF UNITED INDUSTRIES CORP Active

-

Conditionally Registered (03

- Nov

2005) 10

121

- 95 CUTTER INSECT

REPEL LENT 10KA 121 SPECTRUM, A DIV OF UNITED INDUSTRIES CORP Active

-

Conditionally Registered (03

- Nov

2005) 10

121

- 97 CUTTER INSECT

REPELLENT SS 121 SPECTRUM, A DIV O F UNITED INDUSTRIES CORP Active

-

Conditionally Registered 15Page 32 of 45 (29

- Oct

2008)

121

- 99 CUTTER INSECT

REPELLENT 121 SPECTRUM, A DIV OF UNITED INDUSTRIES CORP Active

-

Conditionally Registered (27

- Aug

2008) 20

121

- 100 CUTTER INSECT

REPELLENT 20KA 121 SPECTRUM, A DIV OF UNITED INDUSTRIES CORP Active

-

Conditionally Registered (29

- Oct

2008) 20

806

- 29 AVON SKIN

- SO

SOFT SSS BUG GUARD PLUS PICARIDIN INSECT REPELLENT AEROSOL SPRAY 806 AVON PRODUCTS, INC. Active

-

Conditionally Registered (29

- Aug

2005) 10

806

- 30 AVON SKIN

- SO

SOFT SSS BUG GUARD PLUS PICARIDIN INSECT REPELLENT TOWELETTE(S) 806 AVON PRODUCTS, INC. Active

-

Conditionally Registered (28

- Sep

2006) 10

806

- 31 AVON SKIN

- SO

SOFT SSS BUG GUARD PLUS PICARIDIN INSECT REPELLENT SPRAY 806 AVON PRODUCTS, INC. Ac tive

-

Conditionally Registered (28

- Sep

2006) 10

4822

- 535 KBR 3023 ALL

FAMILY INSECT REPELLENT CREAM II 4822 S.C. JOHNSON & SON INC. Active

-

Conditionally Register ed (07

- Dec

2000) 5

4822

- 536 KBR 3023 ALL

FAMILY INSECT REPELLENT NON

- AEROSOL SPRAY 4822 S.C. JOHNSON & SON INC. Active

-

Conditionally Registered (07

- Dec

2000) 5

4822

- 537 KBR 3023 ALL

FAMILY INSECT REPELLENT AEROSOL SPRAY 4822 S.C. JOHNSON & SON INC. Active

-

Conditionally Registered (07

- Dec

2000) 10Page 33 of 45

4822

- 555 GENEVA

- T 4822 S.C. JOHNSON & SON INC. Active

-

Conditionally Registered (17

- Dec

2007) 16

4822

- 556 GENEVA 4822 S.C. JOHNSON & SON INC. Active

-

Conditionally Registered (17

- Dec

2007) 20

4822

- 564 GENEVA

- P 4822 S.C. JOHNSON & SON INC. Active

-

Condit ionally Registered (09

- Mar

2009) 20

39967

- 48 KBR 3023

TECHNICAL 39967 LANXESS CORPORATION Active

-

Conditionally Registered (07

- Dec

2000) 98.7

39967

- 50 KBR 3023 ALL

FAMILY INSECT REPELLENT CREAM 39967 LANXESS CORPORATION Active

-

Conditionally Registered (30

- Nov

2006) 20

39967

- 53 K BR 3023 ALL

FAMILY INSECT REPELLENT SPRAY 39967 LANXESS CORPORATION Active

-

Conditionally Registered (30

- Nov

2006) 20

54287

- 22 INSECT GUARD

3023 INSECT REPELLENT 54287 ASSOCIATED REGISTRATIONS Active

-

Conditionally Registered (08

- Nov

2007) 20

56575

- 14 NATRAPEL 8

HOUR INSECT REPELLENT WIPES 56575 TENDER CORPORATION Active

-

Conditionally Registered (25

- Mar

2008) 20

56575

- 15 NATRAPEL 8

HOUR INSECT REPELLENT CONTINUOUS SPRAY 56575 TENDER CORPORATION Active

-

Conditionally Registered (15

- Dec

2008) 20

85972

- 1 CENTAURA FLY

AND MOSQUITO 85972 CONVET GMBH & CO. KG Active

-

Condit ionally Registered 20Page 34 of 45 REPELLENT SPRAY (25

- Sep

2009)

86374

- 1 ECOPEL ALL

FAMILY PROTECTION INSECT REPELLENT SPRAY 86374 ECOPEL CORPORATION, LTD Active

-

Conditionally Registered (0 6

- Apr

2010) 20

86459

- 1 FAMILY &

ACTIVE

- USE PROTECTION 86459 NEW HAVEN BRANDS CORP. Active

-

Registered (15

- Aug

2013) 20

121PA1 121 SPECTRUM, A DIV OF UNITED INDUSTRIES CORP Pending (02

-

Dec

- 2008) 20

Total Rows: 29



## Synonym Information For Ingredient

070705 / 119515

- 38

- 7 / Picaridin

Name Type

1

- (1

- Methyl

- propoxycarbonyl)

- 2

- (2

- hydroxyethyl)

- piperidine Other Systematic

1

- Methylpropyl 2

- (2

- hydroxyethyl)

- 1

- piperidine

- carboxylate Other Systematic

1

- Piperidinecarboxylic acid, 2

- (2

- hydroxyethyl)

- , 1

- methylpropyl ester Other Common

KBR 3023 Trade

Picaridin Other Common

Total Rows: 5



## Site/Pest Information For Ingredient 070705 / 119515

- 38

- 7 / Picaridin

Site Information

Go to Pest Info

Site Code Site Name Status Status Date Registration #Page 35 of 45

860110001 HUMAN ANIMAL ATTACK

PREVENTATIVE Pending 20

- Mar

2013 86459

- 1

860030001 CLOTHES Approved 27

- Aug

2008 1 21

- 99

560052606 HORSES (ANIMAL TREATMENT) Approved 17

- Mar

2010 85972

- 1

860020005 HUMAN CLOTHING Approved 21

- Mar

2005 4822

- 537

860030000 HUMAN CLOTHING Approved 04

- Apr

20 05 4822

- 536

860030004 HUMAN CLOTHING Approved 20

- Oct

2005 121

- 91

860020005 HUMAN CLOTHING Approved 03

- Nov

2005 121

- 92

860030004 HUMAN CLOTHING Approved 03

- Nov

2005 121

- 94

860030004 HUMAN CLOTHING Approved 28

- Sep

2006 806

- 31

860020011 HUMAN CLOTHING (FOOTWEAR) Approved 03

- Nov

2005 121

- 92

860020011 HUMAN CLOTHING (FOOTWEAR) Approved 03

- Nov

2005 121

- 94

860020006 HUMAN FACE AREA Approved 29

- Aug

2005 806

- 29

860020006 HUMAN FAC E AREA Approved 20

- Oct

2005 121

- 91

860020006 HUMAN FACE AREA Approved 03

- Nov

2005 121

- 92Page 36 of 45

860020006 HUMAN FACE AREA Approved 03

- Nov

2005 121

- 93

860020006 HUMAN FACE AREA Approved 03

- Nov

2005 121

- 94

860020006 HUMAN FACE AREA Approved 03

- Nov

2005 121

- 95

860020006 HUMAN FACE AREA Approved 25

- Jan

2006 4822

- 536

860020006 HUMAN FACE AREA Approved 28

- Sep

2006 806

- 31

860020006 HUMAN FACE AREA Approved 30

- Nov

2006 39967

- 53

86002000 6 HUMAN FACE AREA Approved 17

- Dec

2007 4822

- 556

860020006 HUMAN FACE AREA Approved 29

- Oct

2008 121

- 97

860020006 HUMAN FACE AREA Approved 29

- Oct

2008 121

- 100

860020006 HUMAN FACE AREA Approved 02

- Dec

2008 54287

- 22

860020006 HUMAN FACE AREA Approved 15

- Dec

2008 56575

- 15

860020006 HUMAN FACE AREA Ap proved 09

- Mar

2009 4822

- 564

860020006 HUMAN FACE AREA Approved 23

- Jun

2009 121

- 89

860020006 HUMAN FACE AREA Approved 23

- Jun

2009 121

- 90Page 37 of 45

860020006 HUMAN FACE AREA Approved 09

- Jun

2010 86374

- 1

860020008 HUMAN NECK AREA Approved 20

- Oct

2005 121

- 91

860020008 HUMAN NECK AREA Approved 03

- Nov

2005 121

- 92

860020008 HUMAN NECK AREA Approved 03

- Nov

2005 121

- 94

860020008 HUMAN NECK AREA Approved 03

- Nov

2005 121

- 95

860020008 HUMAN N ECK AREA Approved 30

- Nov

2006 39967

- 53

860020008 HUMAN NECK AREA Approved 29

- Oct

2008 121

- 97

860020008 HUMAN NECK AREA Approved 02

- Dec

2008 54287

- 22

860020008 HUMAN NECK AREA Approved 23

- Jun

2009 121

- 89

860020008 HUMAN NECK AREA Approved 23

- Jun

2009 121

- 90

860020008 HUMAN NECK AREA Approved 23

- Ju n

2009 121

- 93

860020009 HUMAN SKIN Approved 07

- Dec

2000 4822

- 536

860020009 HUMAN SKIN Approved 07

- Dec

2000 4822

- 537

860020009 HUM AN SKIN Approved 07

- Dec

2000 4822

- 535Page 38 of 45

860020009 HUMAN SKIN Approved 15

- Dec

2004 121

- 89

860020009 HUMAN SKIN Approved 15

- Dec

2004 1 21

- 90

860020009 HUMAN SKIN Approved 29

- Aug

2005 806

- 29

860020009 HUMAN SKIN Approved 20

- Oct

2005 121

- 91

860020009 HUMAN SKIN Approved 03

- Nov

2005 121

- 92

860020009 HUMAN SKIN Approved 03

- Nov

2005 121

- 93

860020009 HUMAN SKIN Approved 03

- Nov

2005 121

- 94

860020009 HUMAN SKIN Approved 03

- Nov

2005 121

- 95

860020009 HUMAN SKIN Approved 28

- Sep

2006 806

- 30

860020009 HUMAN SKIN Approved 28

- Sep

2006 806

- 31

860020009 HUMAN SKIN App roved 30

- Nov

2006 39967

- 50

860020009 HUMAN SKIN Approved 08

- Nov

2007 54287

- 22

860020009 HUMAN SKIN Approved 17

- Dec

2007 4822

- 555

860020009 HUMAN SKIN Approved 17

- Dec

2007 4822

- 556Page 39 of 45

860020009 HUMAN SKIN Approved 25

- Mar

2008 56575

- 14

860020009 HUMAN SKIN Approved 27

- Aug

2008 121

- 99

860020009 HUMAN SKIN Approved 29

- Oct

2008 121

- 97

860020009 HUMAN SKIN Approved 29

- Oct

2008 121

- 100

860020009 HUMAN SKIN Approved 15

- Dec

2008 56575

- 15

860020009 HUMAN SKIN Approved 09

- Mar

2009 4822

- 564

860020009 HUMAN SKIN Approved 09

- Jun

2010 86374

- 1

860020004 HUMANS App roved 30

- Nov

2006 39967

- 53

860020004 HUMANS Approved 17

- Mar

2010 85972

- 1

990000002 MANUFACTURING USE ONLY NO

SITE Approved 07

- Dec

2000 39967

- 48

Total Rows: 66Page 40 of 45



## Appendix D : Picaridin Degradation Pathway

In the absence of abiotic and biodegradation studies, t he Catabol 301c model was used to simulate the environmental degradation for picaridin. The depiction of the degradati on pathway is shown in Figure D

. 1 below

. The degradation pathway from Catabol 301c suggests that picaridin eventually degrades to the degradate picaridin carboxylic acid through a multi

- step process including multiple oxidation and processes. Picaridin

ca rbox ylic acid forms after the second intermediate step in the predicted degradation pathway. This is consistent with wastewater stream monitoring data where picaridin was detected in the influent region and the degradate picaridin carboxylic acid was det ected in the effluent region (Knepper, 2004). Although the wastewater treatment process may have impacted the formation of picaridin carboxylic acid within the stream in the monitoring study, the oxidation processes shown in Figure D .1 demonstrate that th e formation of picaridin carboxylic acid in the environment is plausible as these processes are known to occur naturally in the environment without any wastewater treatment. The first six individual processes for the breakdown aromatic ring structures ori ginating from parent picaridin are shown in Table D .1

. The processes described in Table D .1 correspond to the numbered sections in Figure D .1 . The numbered steps and individual
proc esses are shown until the point that there are no aromatic rings which re m a in intact

.

Table D .1. Process steps for the environmental degradation pathway of picaridin predicted by the Catabol 301c model.

Step Degradation Process 1 Primary hydroxyl group oxidation 2 Aldehyde oxidation 3 Ester hydrolysis 4 Decarboxylation 5 Decarobxylation 6 Oxidative deamination and N

- dealkylation * The numbered steps correspond to the breakdown pathway shown in Figure E.1 below.Page 41 of 45



### Figure D .1. Catabol 301c predicted environmental degradation pathway for picaridin.

Picaridin

Picaridin carboxylic acid

1

2

3

4

5Page 42 of 45



### Figure D .1. Catabol 301c predicted environmental degradation pathway for picaridin (continued).

6Page 43 of 45 

## Appendix E Endangered Species Assessment Information

Based on this screening

- level assessment, there are no potential risks of direct effects to listed species predicted from the use of Picaridin for its registered use. Listed species may also be affected through indirect effects because of the potential direct effects on listed and non

- listed spe cies. Potential direct effects on listed species from the use of Picaridin a ssociated with modification of primary constituent elements o f designated critical habitats is not expected. However, a t this current stage of the Registration Review process, it is premature to make effects determinations for listed species until further refinements are conducted. To make effects determinations for individual species, useful refinements may include analyses of 1) more detailed, species

- specific ecological and bi ological data; 2) more detailed and accurate information on Picaridin use patterns; and 3) sub

- county level spatial proximity data for the co

- occurrence of potential effects areas and listed species and any designated critical habitat. Examples of such

re finements are described below.

EFED is currently developing tools that are expected to further refine the assessment and are designed to support effects determinations for individual federally listed species and their designated critical habitats (where a pplicable). Scientific information obtained from the U.S. Fish & Wildlife Service (USFWS), the National Marine Fisheries Service (NMFS), and other reliable sources is being collated by EFED to address all currently listed species. The information will be stored in an Office of Pesticide Programs Pesticide Registration Information SysteM (PRISM) knowledgebase. The listed species knowledgebase will consist of an information repository that houses biological and behavioral information relevant to individual species ( e.g. , habitat, diet, and life history, including specific temporal and spatial associations) and a document repository that contains supporting documents ( e.g ., USFWS recovery plans) and electronic information ( e.g ., GIS data files). For terrest rial taxa, the biological information relevant to risk quotient (RQ) calculations ( e.g ., diet and body weight) will be used to parameterize exposure estimates to derive species

- specific RQs using a method consistent with currently used methods in the T

- REX and T

- HERPS models.

Refinements may also include more detailed analyses of the registered uses and their use patterns that result in LOC exceedances for federally listed species in the screening

- level assessment. The analyses may include more informat ion on where, when, and how Picaridin is used

. Actual usage data (when available) and national land

- cover datasets that indicate potential use sites [ e.g ., national land cover dataset (NLCD), crop data layer (CDL)] may be used to support a more refined ana lysis of where Picaridin is reasonably expected to be used. Similarly, refinements for the timing of applications and how Picaridin is used may be based on the analysis of additional usage data, beyond what were available at the time of the screening

- leve l assessment, and a more in

- depth exploration of agronomic practices.

The U.S. Environmental Protection Agency, along with the U.S. Department ofPage 44 of 45



### Agriculture (USDA), the U.S. Fish and Wildlife Service (FWS), and the National Marine Fisheries Service (NM FS), have announced the availability of a report developed by the National Academy of Sciences’ National Research Council outlining recommendations on specific scientific and technical issues related to the development of endangered and threatened species risk assessments for pesticides that are compliant with the Endangered Species Act (ESA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The EPA, USDA, FWS and NMFS asked the NRC to consider a range of scientific and technical issues i ncluding:

• identifying best available scientific data and information;

• considering sub

- lethal, indirect and cumulative effects;

• assessing the effects of chemical mixtures and inert ingredients;

• analyzing the effects of pesticide use through the u se of models;

• incorporating uncertainties into the evaluations; and

• using geospatial information and datasets that can be employed by the agencies in the course of these assessments.

After reviewing the NRC’s recommendations on these scientific and technical issues, the EPA and its federal partners will determine how these recommendations can be implemented and incorporated into the scientific approaches for developing listed species risk assessments. It is anticipated that any draft guidance and/or science policies developed by EPA and its federal partners as a result of the NAS recommendations would be released for public comment prior to implementation.

The refinements based on individual species data; additional, detailed usage information, whe n available; and further recommendations from the NRC report are expected to help to more accurately identify potential areas of effect and to better inform effects and habitat determinations for listed species and any designated critical habitats.

For example, if quizalofop

- p

- ethyl is used when a particular species of concern is not present ( e.g ., it is migratory) or is not co

- located in space, then risk of potential direct effects to the species may often be precluded. If LOCs are still exceeded for m onocots, mammals, freshwater invertebrates, estuarine/marine invertebrates, and freshwater fish after conducting the refined analyses, further analyses of the potential spatial and temporal co

- occurrence of listed species of concern (and any designated cri tical habitat) may be conducted. The extent of possible refinement in the analyses of spatial/temporal

co

- occurrence will largely depend on the scale and quality of the available sub

- county level use site ( e.g ., NLCD, CDL) and species location data

.

The Agency has made several refinements to the list of endangered and threatened species that may be affected by quizalofop

- p

- ethyl uses. To date, there are 1442 listed species identified in the LOCATES database (v. 2.2.4, derived from USFWS and NMFS). For 1 295 of these, a “no effect” determination for direct and indirect effects can be made based on a lack of geographical overlap, based on a county level of resolution, between the species and quizalofop

- p

- ethyl uses (Appendix J, Table J

- 1). A further 26
spe cies can be eliminated from consideration of direct effects (i.e., “no effects”) based on species specific ecological and biological information from listed species trustee agenciesPage 45 of 45



### (Appendix J, Table J

- 2). The remaining 121 species will need to be consid ered in more depth before effects calls are made (Appendix J, Table J

- 3). The biological, geographical, and use pattern information outlined above will be necessary to refine the
assessment.