2

In addition to an incomplete exposure pathway based on the use pattern , piperalin has a lo w total usage amount nationally and a relatively limited geographic use. Therefore, EFED has

determined that a full ecological risk assessment for p iperalin is not necessary based on de

minimis exposure

.

This document summarize s the available use, environmental fate, and toxicity data submitted for piperalin and highlight s potential areas of concern or uncert ainty for the single currently registered use.

Based on the indoor

- only use pattern for piperalin and EPA's determination that when the fungicide is used according to the label there is an in complete exposure pathway and, therefore,

no environmental exposure, the Agency makes a No Effects (NE) determination for all listed species a s well as a No Habitat Modification determination for all designated critical habitats f or the currently registered use of piperalin.

The expectation of no e xposure, and therefore no risk, to non

- target organisms in this assessment is based on the presumption that piperalin use is limited to indoors , as is specified on the label

. However, if contaminated potting soil is compost ed outdoors (although piperalin should be highly adsorbed to soil ) or contaminated water is washed out of the greenhouse into surface

waters, the assessment might not be protective

. Therefore, it is recommended that the label state that any potential runoff from contaminated potting soil or water discharged from a greenhouse be contained by a hydrologically isolated site that does not produce runoff capable of entering any irrigation or drainage ditch, canal, or other body of water.

If, in the future, piperalin is considered for addition al uses tha t could result in environmental

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

- target organisms, including l isted species and their designated critical habitat

.3

REGISTRATION REVIEW

Preliminary Ecological Risk Assessment and Endangered Species Effects Determination for:

Piperalin

(CAS Reg. No. 3478

- 94

- 2 ; USEPA PC Code 097003 )

3

- [2

- methylpiperidino]propyl 3,4

- dichlorobenzoate

Prepared by:
Scott Glaberman , Ph

. D

. , Biologist Cheryl Sutton , Ph.D., Environmental Scientist

Reviewed by: Thomas Steeger, Ph.D., Senior Science Advisor Jim Carleton, Ph.D., Senior Fate Scientist Sarah Winfield, Acting Branch Chief

U. S. Environmental 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

March 10 , 20144 TABLE OF CONTENTS

Problem Formulation

................................ ................................ ................................ .... 5 Nature of Regulatory Action

................................ ................................ ................................ ....... 5

Previous Assessments

................................ ................................ ................................ ................. 5 Ecological Risk Assessments

................................ ................................ ...................... 5 Drinking Water Exposure Assessments

................................ ................................ ...... 5

Stressor Source and Distribution

................................ ................................ ................................ 5

Pesticidal Mechanism of Action

................................ ................................ ................. 5 Overview of Pesticide Use and Usage

................................ ................................ ........ 6 Environmental Fate and Transport

................................ ................................ ............................. 6 Ecological Effects

................................ ................................ ................................ ....................... 9 Degradate Toxicity Predictions

................................ ................................ ................. 10 Ecological Incidents

................................ ................................ ................................ .. 10 Characteristics of Ecosystems Potentially at Risk

................................ .................... 11 Conceptual Model

................................ ................................ ................................ ..... 11 Analysis

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

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

................................ ................................ .................. 12

References

................................ ................................ ................................ ................................ . 13 Appendix. ECOSAR Predicted Toxicity Results for Piperalin and Transformation Products. 185

PROBLEM FORMULATION

Nature of Regulatory Action

As part of the implementation of the Registration Review program pursuant to Section 3(g) of FIFRA, the Agency is evaluating all curren t and active registrations for piperalin ( 3

- [2

- methylpiperidino]propyl 3,4

- dichlorobenzoate ) to determine whether it continues to meet the FIFRA standard for registration. The structure of this risk assessment is based on guidance contained in U.S. EPA’s Guidance for Ecological Risk Assessment (USEPA

, 1998a )

, taking into

account criteria present ed by the Office of Pesticide Program’s Science Policy Council/Risk Management Forum De Minimis Subgroup.

Previous Assessments

Ecological Risk Assessments

Piperalin was first registered in the United States in 1964 to treat powdery mildew fungal infections of ornamental plants in greenhouses. The sole current registrant is SePRO Corporation (Carmel, IN). In support of the Reregistration Eligibility Decision (USEPA 1994 a ), an Ecological Risk Assessment (ERA) was conducted (USEPA, 1994 b ) which concluded that there is no significant risk to non

- target terrestrial and aquatic organisms based on the exclusive

indoor commercial greenhouse use pattern.

D rinking Water Ex

posure Assessment s

A drinking water exposure assessment (DWA) in support of a human health risk assessment has

not been conducted in the past based on the indoor

- only (greenhouse) use pattern and consequent

low likelihood of human exposure through drinking water sources

. Similarly, a D WA is not being conducted as part of R egistration Review

.

Stressor Source and Distribution

Piperalin is a fungicide used to control powdery mildew fungal infections of ornamental plants, ornamental woody shrubs and vines

, and trees grown in commercial greenhouses. There is one

end

- use product, Pipron ® (EPA Reg. # 67690

- 1 ; 84.4 % a.i. ), which is formulated as a soluble concentrate/liquid and applied as a foliar spray inside greenhouses

.

The current stamped label (d ated 8/7/2007 ) was accepted by EPA with the condition that the

label specifies : “For use only in commercial greenhouses and similar enclosed structures with nonporous coverings used for the production of ornamental crops for resale .”

Pesticidal Mechanism of Action6

Piperalin’s mechanism of action is inhibit ion of growth and ergosterol biosynthesis in fungal sporidia (Schyneegurt and Henry, 1992).

Overview of Pesticide Use and Usage

Piperalin is supplied as a soluble concentrate/liquid in a s ingle end

- use product (Pipron ® Liquid Concentrate), and is applied by high

- volume, high

- pressure foliar spray to ornamentals only in

commercial greenhouses with an impermeable roof or similar structures . It may not be applied using an irrigation system. Application rates on a per acre basis are not available. The label allows up to 8 fluid ounces of the liquid concentrate product (0.5 lbs a.i.) to be mixed with 100 gallons of water, but does not specify the volume to be applied nor does it limit the numb er of repeat applications. Thus, a maximum application rate cannot be determined from information

on the label

. However, based on information from the registrant (submitted to the Agency in November 2009 as comments upon the opening of the docket EPA

- HQ

- OPP

- 2009

- 0483 for Registration Review of piperalin) , both the median and 90 th percentile use rates are equivalent to

0.125 lb a

. i

. /A. Piperalin may only be used on ornamentals.

Comp rehensive p ast us ag e data are not available, but sales data indicate that a relatively low quantity of piperalin is applied annually. Additionally, the piperalin use is somewhat geographically limited. Based on information presented in the EPA docket for the Registration Review of piperalin ( http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2009

- 0483

- 0018 ), during the one

- year period of 10/1/08 to 9/30/09 , piperalin was on ly sold in five states,

i.e

., CA, FL, MA, TX and UT , with a pproximately 86% of sales in California. Based on information

from the California Department of Pesticide Regulation (CDPR)

, total pounds of piperalin applied annually in California during the years 2005

- 2007 ranged from 2,12 3 to 2,428 lbs

.

Environmental Fate and Transport

A summary of the physical/chemical properties and the environmental fate properties of piperalin is provided in Table 1

. Due to the greenhouse

- only use of piperalin

, several standard

environmental fate studies were not required , as this use pattern does not require submission of

such data under Part 158 Subpart N of Title 40 of the Code of Federal Regulations (abbreviated

40CFR158 1 ).

1 CFR 2014. Code of Federal Regulations Titl e 40 (Protection of the Environment), Part 158 (Data Requirements for Pesticides), Subpart N (Environmental Fate). http://www.ecfr.gov/cgi

- bin/text

idx?tpl=/ecf

rbrowse/Title40/40cfr158_main_02.tpl7

T able 1. Physical/ c hemical p roperties and e nvironmental f ate p rope rties of p iperalin.

Chemical/Fate parameter Value Source (MRID)

Chemical Structure

Molecular Weight (g/mol) 330.25

Vapor Pressure ( T orr; at 25 °C) < 1.0 x 10 - 7 USEPA 2009

Octanol

- water Partition Coefficient (Log K OW ) 4.3 USEPA 2009

Water Solubility (mg/L; at 25 °C) 20 USEPA 2009

Hydrolysis half

- lives (25  C) pH 5 t 1/2 = 714 d pH 7 t 1/2 = 16.4 d pH 9 t 1/2 = 0. 20 d 40407501

43922803

Aqueous photolysis half

- life Not reviewed (not an applicable data requirement for this use type) 41335801

Soil photolysis half

- life Not reviewed (not an applicable data requirement for this use type) 41335802

Aerobic soil metabolism half

- life (pH = 5.5

,

24 °C ) t 1/2 = 96, 100 d (two radio labels) 41425201

43922803

Anaerobic soil metabolism half

- life (pH = 5.5 ) t 1/2 = 33.8, 38. 1 d (two radio labels) 41425202

43922803

Aerobic aquatic metabolism half

- life No data NA

Anaerobic aqu atic metabolism half

- life No data NA

Freundlich adsorption coefficient ( K F ; in L/kg); Parent:

520 (1/n= 0.78 ; clay loam; 2% o.m. )

305 (1/n= 0.87 ; loam; 1.8% o.m. )

62.3 (1/n= 0.73 ; sandy loam; 1.4%

o.m. )

27.6 (1/n= 0.93 ; sand;0.5% o.m.) 42493001

DCBA 1 : 0.2 (1/n= 0.67 )

2.04 (1/n= 0.90)

1.10 (1/n= 0.74)

1.19 (1/n= 0.73) 43922801

MPPA 2 : 0.69 (1/n= 0.93)

0.84 (1/n= 1.1)

1.1 (1/n= 0.96)

3.8 (1/n= 1.4) 439228028

T able 1. Physical/ c hemical p roperties and e nvironmental f ate p rope rties of p iperalin.

Chemical/Fate parameter Value Source (MRID)

Organic carbon

- normalized Freundlich adsorption

coefficient ( K FOC ; in L/kg OC ) Parent:

44824

29212

7672

9516 42493001

DCBA 1 : 67

120

157

70 43922801

MPPA 2 : 41

120

380

225 43922802

Fish bioconcentration and bioaccumulation

factors (BCF /BAF ) BCF: ~1000x

BAF: ~1000x USEPA 2009; Estimated

with KABAM model

1 Major hydrolytic degradate 2,3

- dichlorobenzoic acid

2 Major hydrolytic degradate 3

- (2

- methylpiperidino)propyl alcohol

Piperalin is soluble in water up to 20 mg/L at 25  C and is not expected to volatilize significantly due to the compound’s low vapor pressure of <1 x 10 - 7 T orr at 25  C (USEPA 1994). Piperalin is slightly mobile in low organic carbon soils and hardly mobile in other soils, based on the FAO classification scheme, with organic carbon

- normalized Freundlich adsorption coefficients ( K FOC ) that range from 7672 to 44824 L/kg OC for four soils (MRID 4 2493001 ).

The most significant decay mechanism under most environmental conditions is expecte d to be hydrolysis ( abiotic and microbially mediated )

. Piperalin is susceptible to rapid hydrolysis under

alkaline conditions and hydrolyzes more slowly under neutral conditions, but is relatively stable under acidic conditions (MRID s 404075 0 1, 43922803 ). In soil, piperalin degrades slowly under aerobic conditions (t 1/2 = 98

, 100 d for two radiolabels in one soil type ; MRID 41425201 ) and

somewhat more rapidly under anaerobic conditions (t 1/2 = 34

, 38 d for two radiolabels in one soil
type ; MRID 41425202 )

. Because both test soils were acidic (pH 5.5), more rapid degradation would be expected in more alkaline soils due to more rapid hydrolysis at higher pH levels. Aquatic metabolism data are not available and are not required for the greenhouse use patter n

. Photodegradation data were submitted in 1989 but were not reviewed; the data are not required for the greenhouse use pattern.

Even though there are no empirical data on the bioconcentration or bioaccumulation of piperalin in aquatic ecosystems, a log K
ow > 4 indicates a potential for bioaccumulation if water
contamination should occur . Based on a log K

ow of 4.3, the K

ow - based Aquatic Bio a ccumulation Model (KABAM; http://www.epa.gov/oppefed1/models/water/models4.htm ) was used to estimate that bioaccumulation could occur in aquatic ecosystems

, with factors of approximately 1000x for various size classes of fish with the major route of accumulation occurring through

r espiration (USEPA, 2009)

. However, based on the lack of a complete exposure pathway from9

the use site to non

- target aquatic organisms , ecological effects associated with bioaccumulation of piperalin are not expected.

Two m ajor degradates of piperalin wer e identified in hydrolysis, aer obic and anaerobic soil

studies: the de

- esterification products 2,3

- dichlorobenzoic acid (DCBA) and 3

- (2

- methylpiperidino)propyl alcohol (MPPA). Maximum concentration information for these degradates is presented in Table 2

. Both degradates are more mobile than the parent with K F values ranging from 1.1 to 2.0 L/kg OC in three soils and 0.2 in one soil for DCBA (MRID 43922801)

, and from 0.7 to 3

. 8 for MCPA (MRID 43922802). The adsorption of the degradates is not well correlated with the organic matter content of the soils studied, so the K

oc model may not accurately describe soil mobility across multiple soils for the degradates

.

Table 2. Maximum concentration of piperalin degradates in environm ental fate studies.

Chemical Name MRID Study Type Maximum Concentration (Time) /Final Concentration (time)

2,3

- dichlorobenzoic acid (DCBA) 40407501 Hydrolysis pH 9: 5.2 μg/mL (12 hours ; EOS ) pH 7; 4.7 μg/mL (34 days ; EOS) pH 5; 0.1 μg/mL (34 days ; EOS)

41425201 Aerobic Soil Metabolism 21% (day 14) /48.5% (180)

41425202 Anaerobic Soil Metabolism 58% (day 60; EOS)

3

- (2

- methylpiperidino) propyl alcohol (MPPA) 41425201 Aerobic Soil Metabolism 10.7% (day 3) /2.9% (180)

41425202 Anaerobic Soil Metabolism 14% (day 60 ; EOS) carbon dioxide (CO 2 ) 41425201 Aerobic Soil Metabolism 48.5% (day 180 ; EOS) EOS = End of study.

Ecological Effects

Effects to Aquatic Organisms

Piperalin is classified as highly toxic to freshwater fish and moderately toxic to freshwater invertebrates ( Table 3 ) on an acute exposure basis . No chronic toxicity data are available for freshwater aquatic anim als. In addition, no data are available to describe the toxicity of piperalin

to estuarine /marine fish or invertebrates

, or aquatic vascular or nonvascular plants.

Table 3 . Summary of most sensitive endpoints from submitted aquatic toxicity studies for piperalin

.
Species (common name) Taxa

Represented End

point Duration

(hours) Mean

C oncentration (μg a.i./L) Citation

MRID Study

Classification

Lepomis macrochirus (Bluegill Sunfish) Freshwater fish and aquatic

phase amphibians LC 50 96 770

(highly toxic) 43012201 Acceptable

Daphnia magna (Water Flea) Freshwater

Invertebrates LC 50 48 1890
(moderately toxic) 40407504 Acceptable10

Effects to Terrestrial Organisms

Piperalin is classified as practically non

- toxic to birds on a sub

- acute dietary exposure basis and slightly toxic to mammals on an acute oral exposure basis ( Table 4) . There are no data on the chronic effects of piperalin on birds or mammals . There are no data o n the effects of piperalin to terrestrial plants. Piperalin is practically non

- toxic to honey bees ( Apis mellifera ) on an acute contact exposure basis.

Table 4 . Summary of most sensitive endpoints from submitted terrestrial toxicity studies

for piperalin ( NR=not reported ).

Species

(common name) Taxa

Represented End

point Mean

Concentration Test

Substance (% a.i.) Citation

MRID Acute

Toxicity

Classification

Rattus norvegicus

(Fisher 344 Rat) Mammals LD 50 800 mg/kg (female)

1419 mg/kg (male) 99 40503201 Slightly toxic

Colinus virginianus

(Northern

Bobwhite Quail) Birds L C 50 > 5,380 mg/kg

- diet 99 40407502 Practically

non

- toxic

Apis mellifera (Honey Bee) Terrestrial

insects LD 50 > 36.26 μg/bee 1 NR 00018842 Practically

non

- toxic

1 Two percent mortality occurred at the highest concentration tested (36.26 μg/bee)

Degradate Toxicity Predictions

Ecological effects data are not available for the two major degradates of piperalin, DCBA and

MPPA. In order to comp are potential toxicity of transformation products to the parent , estimated toxicity data for piperalin and degradates were generated using quantitative structure

- activity relationships (QSAR ) derived in the program ECOSAR (version 1.11) (see Appendix A for program output) . QSAR es timates for the parent compound for fish acute toxicity (LC 50 range: 625 to 810 μg a.i./L ) are very similar to the empirical endpoint for piperalin (LC 50 = 770 μg a.i./L ), regardless of whether these estimates are based on a specific chemical class (i.e., aliphatic

amines ) or baseline toxicity (i.e., neutral organics). QSAR estimates of the toxicity of piperalin to daphnids overestimate the empirical endpoint for piperalin (LC 50 = 1890 μg a.i./L ) based on

the class aliphatic amines (LC 50 = 154 μg a.i./L ), b ut were more accurate for the ester class (LC 50 = 1070 μg a.i./L ). Overall, QSAR toxicity predictions suggest that degradates are either of equal or lower toxicity than the parent compound across fish, aquatic invertebrates, and algae.

Ecological Inciden ts11

A review of the Ecological Incident Information System (EIIS) maintained by the Agency’s Office of Pesticide Programs (OPP) in January 2014 indicates that there are no reported ecological incidents associated with the use of piperalin

. A review of OPP’s Incident Data System (IDS) in February 2014 indicates that there was one incident in which the product Pipron ® was associated with minor damage to plants

. A search of the American Bird Conservancy’s Avian Incident Monitoring System (AIMS) Database in January 2014 did not indicate any reported incidents in birds involving the use of piperalin. In general, an absence of reported incidents cannot be construed as the absence of incidents though.

Characteristics of Ecosystems Po tentially at Risk

As previously discussed, piperalin is registered for use only in enclosed commercial greenhouses with impermeable roofs and, as such, exposure to non

- target aquatic and terrestrial organisms is not expected. As such, no ecosystem is lik ely to be at risk from the indoor use of this compound.

Conceptual Model

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically significant concentrations. An exposure pathway is the means by which a pesticide mov es in the environment from a source to an ecological receptor. For an ecological pathway to be complete, it must have a source, a release mechanism, an environmental transport medium, a point of exposure for ecological receptors, and a feasible route of e xposure.

The conceptual model for piperalin provides a written description and visual representation of the predicted relationships between piperalin, potential routes of exposure, and the predicted effects for the assessment endpoint. A conceptual model consists of two major components: risk hypothesis and a conceptual diagram (USEPA 1998).

Risk Hypothesis

A risk hypothesis describes the predicted relationship among the stressor, exposure, and assessment endpoint response along with the rationale for t heir selection. For piperalin, the following ecological risk hypothesis is being employed for this ecological risk assessment:

Piperalin , when used indoor s in accordance with the label, is not expected to result in adverse effects on the survival, growth , and reproduction of non

- target terrestrial and /or aquatic organisms (plants and animals)

.

Conceptual Diagram

A c onceptual diagram/model is established for chemicals with likely outdoor environmental exposure pathways. This is not the case for piperalin , which is used indoors and does not have

outdoor uses. As such, this problem formulation does not depict a conceptual diagram for the indoor use of piperalin.12

For the sole currently registered use of piperalin, potential ecological exposure i s expected to be

de minimis based on the lack of a complete exposure pathway from the use site to non

- target terrestrial and aquatic organisms.

Analysis

T he use, environmental fate, and ecological effects are characterized and integrated to assess the

r isks. This is accomplished using a risk quotient ( RQ; ratio of exposure concentration to effects concentration) approach when possible

. When a RQ approach is not possible, risks are assessed qualitatively. Because piperalin is used indoors only, and in a relatively low quantity on a national basis, environmental exposure is not expected. Therefore, risk to non

- target listed and

non

- listed organisms will not be assessed.

Endangered Species Assessment

Based on the indoor

- only use pattern for piperalin, and EPA's determination that, when piperalin

is used according to the label, environmental exposure is not expected

, the Agency makes a No Effects (NE) determination for all listed species and a No Habitat Modification determination for all designated crit ical habitats for the currently registered use of piperalin within greenhouses

.

If, in the future, piperalin is considered for additional uses that could result in environmental exposures, further analysis will need to be undertaken to determine potential effects to listed species and their designated critical habitat

.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, E PA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, r eproductive 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 the most recent registrat ion decision for piperalin, 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), piperalin is subject to the endocrine scr eening 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 ident ify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will p roceed to the next stage of the EDSP where EPA13

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and

establish a dose

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67

c hemicals, 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 2 and includes some pesticides scheduled for registration review and chemicals found i n water. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our

website. 3

Uncertainties

The expectation of no exposure to non

- target organisms in this assessment is based on the presumption that piperalin use is limited to indoors , as specified on the label . However, if

contamin ated potting soil is compost ed outdoors (although piperalin should be highly adsorbed

to soil ) or contaminated water is washed out of the greenhouse into surface waters, the

assessment might not be protective , and there would be uncertainty as to the potential adverse effect of piperalin on non

- target organisms due to exposure

.

References

FAO. 2000. Appendix 2. Parameters of pesticides that influence processes in the soil . In FAO Information Division Editorial Group (Ed.), Pesticide Disposal Series 8. Assessing Soil Contamination. A Reference Manual. Rome: Food & Agriculture Organization of the United Nations (FAO).

Schyneegurt, M.A. and M. J. Henry. 1992. Effects of piperalin and fenpropidin on sterol biosynthesis in Ustilago maydis. Pesticide biochemistry and physiology 43: 45

- 52.

U SEPA. 1994 a

. USEPA. 1994a. Reregistration Eligibility Decision (RED) Piperalin. Office of Pesticide Progr ams, United States Environmental Protection Agency. Washington, D.C. July 1994. (EPA 738

- R

- 94

- 033)

USEPA. 1994b

. USEPA. 1994b. Piperalin RED (Reregistration Eligibility Document). (sic) Environmental Fate and Effects Division, Office of Pesticide Pro grams, United States Environmental Protection Agency. Washington, D.C. September 1994. (DP Barcodes: 183913, 200603)

.

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.

3 http://www.epa.gov/endo/14

USEPA. 1998a. Guidance for Ecological Risk Assessment. Risk Assessment Forum.

EPA/630/R

- 95/002F, April 1998.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. Office of Prevention, Pesticides, and Toxic Substances. Office of Pesticide Programs. Washington, D.C. January 23, 2004.

USEPA. 2007b. Ecological Incide nt Information System. http://www.epa.gov/espp/consultation/ecorisk

- overview.pdf

.

USEPA. 20 09

. Registration Review : Preliminary Problem Formulation for Ecological Risk,

Environment al Fate, Endangered Species, and Drinking Water Assessments for Piperalin. Office of Pesticide Programs, United States Environmental Protection Agency. Washington, D.C. May 28, 2009

. (DP Barcode: 364402)

U.S. Fish and Wildlife Service (USFWS) and National Marine Fisheries Service (NMFS). 1998. Endangered Species Consultation Handbook: Procedures for Conducting Consultation and Conference Activities Under Section 7 of the Endangered Species Act. Final D raft.

March 1998.15

Environmental Fate Studies

161

- 1 Hydrolysis

MRID Citation Reference

93185018 Registrant

summary Environ Corp. (1990) Elanco Products Co. Phase 3 Summary of MRID

40407501. Hydrolysis of Piperalin in Buffer Solution: Study No. AAC8718. Prepared by Lilly Research Laboratories. 10 p.

40407501 2067281 Koenig, D.K. 1987 Hydrolysis of Piperlin in Buffer Solution

161

- 2 Photodegradation

- water

MRID Citation Reference

41335801 DER not

located Dykes, J. (1989) Determination of the Photolysis Rate of [Carbon

- 14]

- piperalin

in Aqueous Solution: ABC Final Report 37686; 211/EWPHOT/US. Unpublished study prepared by Analytical Bio

- Chemistry Laboratories, Inc. 34 p.

161

- 3 Photodegradatio n

- soil

MRID Citation Reference

41335802 DER not

located Jackson, S.; Kesterson, A.; Lawrence, L. (1989) Soil Surface Photolysis of

[Carbon

- 14] Piperalin in Natural Sunlight: Lab Project No. 353; Report 1219; 211/ESPHOT/AM. Unpublished study prepared by Pharmacology and Toxicology Research Laboratory. 68 p.

162

- 1 Aerobic soil metabolism

MRID Citation Reference

41425201 2067282 Rainey, D. (1990) Aerobic Soil Metabolism of ?Carbon 14| Piperalin: Lab I.D. Number ABC0430. Unpublished study prepared by DowElanco, Plant Science Chemical Development. 33 p.

162

- 2 Anaerobic soil metabolism

MRID Citation Reference

41425202 2067283 Rainey, D. (1990) Anaerobic Soil Metabolism of ?Carbon 14| Piperalin Lab I.D. Number: ABC0431. Unpublished study prepared by DowElanco, Plant Science Chemical Development. 32 p.

163

- 1 Leach/adsorp/desorption

MRID Citation Reference

41425203 2067284 Saunders, D. (1990) Piperalin Aged Soil Leaching Study: Lab I.D. Number: DGS8902. Unpublished study prepared by DowElanco, Plant Science Chemical16 Development. 37 p.

42493001 2067285 Saunders, D.; Powers, F. (1988) Adsorption and Desorpt ion of Piperalin on Soil: Lab Project Number: EWD8729. Unpublished study prepared by Lilly Research Laboratories. 63 p.

43922801 2067286 Kennard, L.; Saunders, D. (1996) Soil Adsorption and Desorption of 2,3

- Dichlorobenzoic Acid, a Degradate of Piperalin : Lab Project Number: ENV95138. Unpublished study prepared by DowElanco North American Environmental Chemistry Lab. 82 p.

43922802 2067287 Sanders, L.; Saunders, D. (1996) Soil Adsorption and Desorption of 3

- (2

- Methylpiperidino)proply Alcohol, a Degradat e of Piperalin: Lab Project Number: ENV95139. Unpublished study prepared by DowElanco North American Environmental Chemistry Lab. 84 p.

N on

- Guideline

43922803

Reviewed with

43922801 and 802 2067289 Saunders, D.; Powers, F. (1996) Confirmation of Degrada tes of Piperalin: Lab Project Number: ENV95140. Unpublished study prepared by DowElanco North American Environmental Chemistry Lab. 84 p.

Ecological Effects Studies

71

- 2 Avian Dietary Toxicity

MRID Citation Reference

40407502 2067291 Negilski, D.; Meyerhoff, R. (1987) The Toxicity of Piperalin to Juvenile

Bobwhite in a Five

- day Dietary Study: Laboratory Pro

- ject ID: A00487. Unpublished study prepared by Lilly Research Laboratories. 38 p.

93185004 Summary of

above Environ Corp. (1990 ) Elanco Products Co. Phase 3 Summary of MRID

40407502. The Toxicity of Piperalin to Juvenile Bobwhite in a Five

- Day Dietary Study: Study No. AOO487. Prepared by Lilly Research Laboratory. 15 p.

72

- 1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

124479 What animals? Worth, H.; Gibson, W.; Anderson, R. (1965) Acute Toxicity Studies in Animals with Pipron E.C. (Unpublished study received Nov 29, 1965 under 1471

- 58; submitted by Elanco Products Co., Div. of Eli Lilly and Co., Indianapolis, IN;

CDL:006295

- A)

40407503 2067292

invalidated Negilski, D.; Grothe, D.; Seacat, J. (1987) Acute Toxicity of Pi

- peralin to

Bluegill (Lepomis macrochirus ) in a Flow

- through Test System: Laboratory Project ID: F01287. Unpublished study pre

- pared by Lilly Research Laboratories. 36 p.

43012201 2067294 Weinberg, J.; Kirk, H.; Miller, J.; et al. (1993) Evaluation of the Acute Toxicity of Piperalin to the Bluegill, Lepomis macrochirus Rafinesque: Lab Project

Number: DECO

- ES

- 2722. Unpublished study prepared by Dow Chemical Environmental Toxicity & Chemistry Research Lab. 27 p.17

40098001 2049421 Mayer and Ellersieck, USFWS

- Goldfish LC50

93185005 Summary of

above Environ Corp. (1990) Elanco Products Co. Phase 3 Summary of MRID

40407503. Acute Toxicity of Piperalin to Bluegill (Lepomis macrochirus) in a

Flow

- Through Test System: Study NO.F01287. Prepared by Lilly Research Laboratories. 12 p.

72

- 2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

40407504 2067293 Negilski, D.; Grothe, D.; Mohr, R. (1987) Acute Toxicity of Pipera

- lin to Daphnia magna in a Static

- renewal Test System: Laboratory Project ID: C00887. Unpublished study prepared by Lilly Re

- search Laboratories. 36 p.

93185006 Summary of

above Environ Corp. (1990) Elanco Products Co. Phase 3 Summary of MRID

40407504. Acut e Toxicity of Piperalin to Daphnia magna in a Static

- Renewal Test System: Study No.C00887. Prepared by Lilly Research Laboratories. 12 p.18

Appendix . ECOSAR Predicted Toxicity Results f or Piperalin and Transformation

Products.

(Piperalin)

SMILES: CC1CCCCN1CCCOC(=O)c2cc(CL)c(CL)cc2
CHEM: Piperalin

MOL FOR: C16 H21 CL2 N1 O2

MOL WT : 330.26
Log Kow: 5.08 (KowWin estimate) Wat Sol: 20 mg/L (experimental database)

ECOSAR v1.00 Class(es) Found

------------------------------ ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Aliphatic Amines : Fish 96

- hr LC50 0.810
Aliphatic Amines : Daphnid 48

- hr LC50 0.154
Aliphatic Amines : Green Algae 96

- hr EC50 0.180
Aliphatic Amines : Fish ChV 0.018
Aliphatic Amines : Daphnid ChV 0.020
Aliphatic Amines : Green Algae ChV 0.032
Aliphatic Amines : Fish (SW) 96

- hr LC50 0.887
Aliphatic Amines : Mysid Shrimp (SW) 96

- hr LC50 0.136
Aliphatic Amines : Green Algae (SW) 96

- hr EC50 0.175
Aliphatic Amines : Fish (SW) ChV 0.018
Aliphatic Amines : Mysid Shrimp (SW) ChV 0.020
Aliphatic Amines : Green Algae (SW) ChV 0.033

Esters : Fish 96

- hr LC50 0.775

Esters : Fish 14

- day LC50 1.094
Esters : Daphnid 48

- hr LC50 1.070
Esters : Green Algae 96

- hr EC50 0.327
Esters : Fish 32/33

- d ChV 0.033
Esters : Daphnid 21

- day ChV 0.305
Esters : Green Algae ChV 0.225
Esters : Fish (SW) 96

- hr LC50 0.850
Esters : Mysid Shrimp 96

- hr LC50 0.220
Esters : Fish (SW) ChV 0.222 !
Esters : Mysid Shrimp (SW) ChV 0.026

Esters : Earthworm 14

- day LC50 436.285 *

==================== ======= ================== ======== ====== ========== Neutral Organic SAR : Fish 96

- hr LC50 0.625
(Baseline Toxicity) : Daphnid 48

- hr LC50 0.524
: Green Algae 96

- hr EC50 0.800

: Fish ChV 0.055
: Daphnid ChV 0.083

: Gree n Algae ChV 0.509 =

Note: * = asterisk designates: Chemical may not be soluble
enough to measure this predicted effect.

Note: ! = exclamation designates: The toxicity value was determined from a predicted
SAR using established acut e

- to

- chronic ratios and ECOSAR regression techniques which
are documented in the supporting Technical Reference Manual. When possible, this
toxicity value should be considered in a weight of evidence approach.19

( DCBA )

SMILES : OC(=O)c1cccc(CL)c1CL

CHEM : DCBA

MOL FOR: C7 H4 CL2 O2

MOL WT : 191.01
Log Kow: 2.82 (KowWin estimate) Wat Sol: 189.4 mg/L (WskowWin estimate)

ECOSAR v1.00 Class(es) Found

------------------------------ Neutral Organics

- acid

Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ==========

-- > Acid moeity foun d: Predicted values multiplied by 10

Neutral Organics

- acid : Fish 96

- hr LC50 279.034 * Neutral Organics

- acid : Fish 14

- day LC50 285.893 * Neutral Organics

- acid : Daphnid 48

- hr LC5 0 177.647
Neutral Organics

- acid : Green Algae 96

- hr EC50 120.443
Neutral Organics

- acid : Fish 30

- day ChV 30.715
Neutral Organics

- acid : Daphnid ChV 23.455

Neutral Or ganics

- acid : Green Algae ChV 52.773
Neutral Organics

- acid : Fish (SW) 96

- hr LC50 364.474 * Neutral Organics

- acid : Mysid Shrimp 96

- hr LC50 154.932
Neutral Organics

- acid : Fish (SW) ChV 65.141
Neutral Organics

- acid : Mysid Shrimp (SW) ChV 10.500
Neutral Organics

- acid : Earthworm 14

- day LC50 2729.851 * Note: * = asterisk designates: Chemical may not be solub le

enough to measure this predicted effect.

(MPPA)

SMILES : C1CCCCN(C(C1)C)CCCO

CHEM : MPPA

MOL FOR: C11 H23 N1 O1

MOL WT : 185.31
Log Kow: 2.32 (KowWin estimate) Wat Sol: 5551 mg/L (WskowWin estimate)

ECOSAR v1.00 Class(es) Found

------------------------------ Aliphatic Amines

Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== == ====== ====== ========== Aliphatic Amines : Fish 96

- hr LC50 20.993
Aliphatic Amines : Daphnid 48

- hr LC50 2.260
Aliphatic Amines : Green Algae 96

- hr EC50 1.0 75 Aliphatic Amines : Fish ChV 0.372
Aliphatic Amines : Daphnid ChV 0.020
Aliphatic Amines : Green Algae ChV 0.392
Aliphatic Amines : Fish (SW) 96

- hr LC50 22.458
Aliphatic Amines : Mysid Shrimp (SW) 96

- hr LC50 2.133
Aliphatic Amines : Green Algae (SW) 96

- hr EC50 1.052
Aliphatic Amines : Fish (SW) ChV 0.37220

Aliphatic Amines : Mysid Shrimp (SW) ChV 0.020
Aliphatic Amines : Green Algae (SW) ChV 0.376

=========================== ================== ======== ====== === ======= Neutral Organic SAR : Fish 96

- hr LC50 77.022
(Baseline Toxicity) : Daphnid 48

- hr LC50 46.178
: Green Algae 96

- hr EC50 22.671

: Fish ChV 7.261
: Daphnid ChV 4.511
: Green Algae ChV 8.693

Note: * = asterisk designates: Chemical may not be soluble

enough to measure this predicted effect.