### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 2 of 66 Tralopyril Registration Review Team

Human Health Timothy Dole Jonathan Chen Zoe Layton

Environmental Fate and Effects Zoe Layton Srinivas Gowda James Breithaupt Siroos Mostaghimi

Risk Management Wanda Henson Lance Wormell

Office of General Counsel Philip Ross

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

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## Table of Contents
1 Introduction .................................................................................................................. ........... 5 1.1 Statutory and Regulatory Authority ................................................................................. 5 1.2 Case Overview ................................................................................................................. 7 1.3 Chemical Identification and Properties ............................................................................ 7 1.4 Use/Usage Description ..................................................................................................... 9 1.4.1 Summary of Regist ered Uses .................................................................................... 9 1.4.2 Usage Information .................................................................................................. 10 1.5 Regulatory History ......................................................................................................... 10 1.5.1 Recent/Pending Regulatory Actions ....................................................................... 10 1.5.2 Tolerance Information ............................................................................................ 10 1.6 Incidents ..................................................................................................................... .... 10 1.6.1 Human Health ......................................................................................................... 10 1.6.2 Ecological ............................................................................................................... 10 2 Anticipated Data Needs ........................................................................................................ 11 3 Human Health Risk Assessment ........................................................................................... 14 3.1 Dietary Exposure .......................................................................................................... ...... 16 3.1.1 Food ................................................................................................................... ......... 16 3.1.2 Drinking Water ......................................................................................................... .. 16 3.2 Occupational and Resi dential Exposures ............................................................................ 17 3.2.1 Occupational Handler Exposure .................................................................................. 17 3.2.2 Residential Handler Exposures .................................................................................... 18 3.2.3 Residential Post-Application Exposures ...................................................................... 19 3.3 Aggregate and Cumulative Exposure ................................................................................. 19 3.3.1 Aggregate Exposures ................................................................................................... 1 9 3.3.2 Cumulative Exposures ................................................................................................. 20 4 Environmental Risk Assessment........................................................................................... 20 4.1 Environmental Fate and Exposure Pathways ................................................................. 21 4.2 Ecological Effects Assessment ....................................................................................... 24 4.2.1 Mode of Action ....................................................................................................... 24 4.2.2 Measures of Effect (Ecotoxicology Assessment Endpoints) .................................. 24 4.3 Exposure Analysis Plan .................................................................................................. 29 4.3.1 Aquatic and Terrestrial Wild life Exposure Estimates ............................................ 29 5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 30 6 Optional Label Changes ........................................................................................................ 30 7 Guidance for Commentors .................................................................................................... 31 7.1 Preliminary Work Plan ................................................................................................... 31 7.1.1 Trade Irritants .......................................................................................................... 31 7.1.2 Water Quality .......................................................................................................... 31 7.1.3 Environmental Justice ............................................................................................. 31 7.1.4 Structure Activity Relationships ............................................................................. 32 7.1.5 Additional Information ........................................................................................... 33 8 Next Steps .................................................................................................................... ......... 33 9 References .................................................................................................................... ......... 33

Appendix A Toxicology Profile ............................................................................................... 42

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 4 of 66 Appendix B Environmental Fate ............................................................................................. 49 Appendix C Ecotoxicology Profile .......................................................................................... 57

List of Tables Table 1 – Summary of Anticipated Risk A ssessments and Data Needs: Tralopyril ...................... 6 Table 2 – Anticipated Regist ration Review Schedule .................................................................... 6 Table 3 – Chemical Identification of Tralopyril ............................................................................. 7 Table 4 – Physical-Chemical Properties for Tralopyril ................................................................. 8 Table 5 – Chemical and Physical Prop erties of Tralopyril Degradates .......................................... 9 Table 6 – Summary of Tralopyril Registered Uses ...................................................................... 10 Table 7 – Studies Anticipated as Needed fo r the Registration Review of Tralopyril ................... 12 Table 8 –Existing Toxicological Endpoints for Dietary Exposure to Tralopyril .......................... 14 Table 9 – Existing Toxicological Endpoints for Occupational/Residential Exposure to Tralopyril

............................................................................................................................... ........................ 15 Table 10 – Occupational Handler Ex posure Scenarios for Tralopyril .......................................... 18 Table 11 – Residential Handler Exposu re Scenarios for tralopyril .............................................. 19 Table 12 – Selected Effects Endpoints for the Ecological Risk Assessment of Tralopyril .......... 25 Table 13 - Selected Effects Endpoints for the Ec ological Risk Assessment of Tralopyril's Major Degradate CL322,250 ........................................................................................................... ........ 26 Table 14 - Selected Effects Endpoints for the Ec ological Risk Assessment of Tralopyril's Major Degradate CL322,248 ........................................................................................................... ........ 28 Table 15 - Acute Toxicity Data for tralopyril ............................................................................... 4 2 Table 16 - Summary of parent tralopyril half-l ives and degradate amounts and half-lives in environmental fate studies .................................................................................................... ........ 51 Table 17 - Sorption (Kf/Koc) of parent tralopyril and its main degradates .................................. 52 Table 18 - Physical-Chemical Properties fo r Tralopyril and its Primary Metabolites ................. 52 Table 19 – Reviewed and Accepted Paint Leachi ng Studies for Tralopyril in Seawater ............. 53 Table 20. Toxicity Profile of Tralopyr il Parent and Degradates to Birds .................................... 58 Table 21. Toxicity Profile of Tralopyril Parent and Degradates to Freshwater Fish, Acute and Chronic ....................................................................................................................... ................... 59 Table 22 – Toxicity Profile of Tr alopyril Parent and Degradates to Freshwater Invertebrates, Acute and Chronic ............................................................................................................. ........... 60 Table 23. Toxicity Profile of Tralopyril Parent and Degradates to Estuarine and Marine Fish, Acute and Chronic ............................................................................................................. ........... 61 Table 24. Toxicity Profile of Tralopyril Parent and Degradates to Estuarine and Marine Invertebrates, Acute and Chronic .............................................................................................. ... 62 Table 25. Toxicity Profile of Tralopyril Parent and Degradates to Be nthic Invertebrates, Freshwater and Estuarine/Marine ............................................................................................... .. 64 Table 26. Toxicity Profile of Tral opyril Parent and Degradates to Terristrial/Semi Aquatic Plants

............................................................................................................................... ........................ 64 Table 27. Toxicity Profile of Tralopyril Pare nt and Degradates to Aquatic Plants ..................... 65

List of Figures Figure 1 – Conceptual Model for Ecological Expo sure and Effects of Tralopyril to Aquatic Organisms from the Antifoulant Use ............................................................................................ 24

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# 1 Introduction

This document is the Environmen tal Protection Agency’s (EPA or “the Agency”) Preliminary Work Plan (PWP) for tralopyril. This case was originally titled “econea” and has since been renamed “tralopyril” to replace the trade name with the generic active ingredient name. The PWP document explains what EPA's Office of Pesticide Programs knows about tralopyril, highlighting anticipated data and assessment need s, identifying the types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timeline for completing tralopyril’s review.

The registration review process was designed to include a publi c participation component to solicit input from interested stake holders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows ab out tralopyril and what types of new data or other information would be helpful for the Agen cy to receive as it moves toward a decision on tralopyril. The Agency encourages all interested stakeholders to review the PWP and to provide comments and additional information that will he lp the Agency’s decision-making process for this chemical.



## 1.1 Statutory and Regu latory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the U.S. Environmental Protection Agency (USEPA, EPA, or the Agency ) based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The regist ration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet th e statutory standard of no unreas onable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs , products in the marketpl ace can be used safely. Information on this program is provided at http://www.epa.gov/oppsrrd 1/registration_review/.

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registra tion review begin at 40 CFR 155.40. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registrati on review decision. After reviewing and responding to comments and data received in the docke t during this initial comment period, the Agency will develop and commit to a Final Work Plan (FWP) and anticipated schedule for the Tralopyril Case.

Documents associated with this registration re view can be viewed at http://www.regulations.gov in docket EPA-HQ-OPP-2013-0217. Below is a summ ary of the issues relevant to this registration review case.

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 6 of 66 Table 1 – Summary of Anticipated Risk A ssessments and Data Needs: Tralopyril

Risk Assessment Assessment Necessary to Support Registration Review Date of Most Recent Assessment Type of Assessment Required (New/Updated) Data Anticipated as Needed (See Table 7 for more detail about anticipated data needs)

Dietary (food) No N/A None None Dietary (drinking water) Yes 4/16/08 Updated None

Occupational Handler Yes 2/15/2007 Updated Dermal Exposure, Outdoor Inhalation Exposure

Residential Handler Yes 4/10/2008 Updated Dermal Exposure, Outdoor Inhalation Exposure Aggregate Yes None New None

Cumulative No None None None

Tolerance Review No N/A None None

Ecological Yes 4/24/2007 Updated Leaching data in fresh water

Avian reproduction study

Acute zebra fish study or a rainbow trout fish early life stage study

Freshwater benthic i nvertebrate chronic reproduction study one with an amphipod and one with a chironomid for the parent

Saltwater benthic invertebrate with an amphipod

pKa values

Log Kow values N/A = Not applicable



### Table 2 – Anticipated Regi stration Review Schedule
Anticipated Activity Target Date* Completion Date Phase 1: Openin g the Docket Open Docket and 60-Day Comment Period for Preliminary Work Plan 2013-06 [Year-MM-DD] Close Public Comment Period 2013-08 Phase 2: Case Development Issue Final Work Plan 2013-12 Issue Data Call-In (DCI) 2014-12 Receive Data to be Considered in Risk Assessment 2017-12 Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2019-06 Close Public Comment Period 2019-07 Phase 3: Registration Review Decision and Implementation Open 60-Day Public Comment Period for Proposed Decision 2019-12 Close Public Comment Period 2020-02

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 7 of 66 Issue Final Decision 2020-06 Begin Post-Decision Followup 2020 Total (years) 7 *The anticipated schedule will be revised as necessary ( e.g ., need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case).



## 1.2 Case Overview
The docket for the tralopyril Case (Case 5114) has been established at http://www.regulations.gov in docket number EPA-HQ-OPP-2013-0217.



## 1.3 Chemical Identification and Properties

Table 3 presents the active ingredient to be assessed in Case 5114, tr alopyril (PC Code 119093).

Table 3 – Chemical Identi fication of Tralopyril

Common Name Tralopyril

Chemical Names 1H-Pyrrole-3-carbonitrile,4-bromo-2-(4-chlorophenyl)-5-(trifluoromethyl)-; Pyrrole-3-carbonitrile, 4-bromo-2-(p-chlorophenyl)-5-(trifluoromethyl); 2-(p-chlorophenyl)-3-cyano-4-bro mo-5-trifluoromethyl pyrrole; Tralopyril Classification Halogenated Pyrrole Nitrile PC Code 119093 Common Name Tralopyril CAS No. 122454-29-9 Molecular Formula C 12 H 5 BrClF 3 N 2 Molecular Weight 349.53 g/mol Available Bromine 45.72% Available Chlorine 20.28% Available Fluorine 32.62%

Molecular Structure:



### The parent tralopyril product chemis try information (source: MRIDs 45673902, 45673903, 45673906, 45673907 and 48596802) relevant to risk assessm ent is summarized in Table 4 and details of the environmental fate proper ties are discussed in Appendix B.

Table 5 below contains the chem ical and physical properties of the tralopyril degradates CL 322,250, CL 322,248, and CL 325,195.

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 8 of 66 Table 4 – Physical-Chemical Properties for Tralopyril

Guideline Number Physical and Chemical Properties Value

830.1500 Product Identity and Composition Refer to Table 3 830.1650 Description of Formulation Process Confidential Business Information (CBI) 830.1800 Enforcement Analytical Method HPLC Method M-3408.01

830.6302 Color Pale yellow-brown Beige White powder Off-White powder

830.6303 Physical State Powder Solid at room temperature. 830.6304 Odor Slightly sweet, marzipan-like odor

830.6313 Stability to normal and elevated temperature, metals/metal ions The test substance was stable after incubation for 14 days at 54  C and is stable in the presence of copper and iron.

830.6314 Oxidation/Reduction: Chemical Incompatibility: Oxidizer. Materials to avoid: Strong Oxidizing Agents. 830.6315 Flammability The TGAI is not combustible/flammable. 830.7000 pH 5.16 (0.1% w/v dispersion in dist. water).

830.7050 UV/Visible Absorption The wavelengths of maximum absorbance are as follows: 281.4, 281.9, and 223.9 for acidic, neutral and alkaline conditions, respectively.

830.7200 Melting point Examination of the differential scanning calorimetry endotherms with programmed heating indicated that melting starts at 252.3  C (525.5 K), with a peak at 253.4  C (526.6 K). No decomposition was observed at temperatures below 400  C. 830.7220 Boiling point Not applicable (TGAI is solid). 830.7300 Density 1.714 g/cm 3 at 20oC 830.7370 Dissociation Constant in water pKa = 7.08 at 26  C

830.7550 Partition coefficient ( n

octanol/water) Log K ow 3.5

830.7840 Solubility in water Water solubility by column elution at 20  C:

 0.17 mg/L in unadjusted water (nominal pH of 4.9) and

 0.16 mg/L in seawater (nominal pH of 8.1).

830.7860 Solubility in Organic solvents at 20°C Acetone 300.5 g/L Ethyl acetate 236.0 g/L n-Heptane 7.2 g/L Methanol 109.1 g/L n-Octanol 85.2 g/L Xylene 5.6 g/L

830.7950 Vapor pressure 1.42 x 10 -10 mm Hg at 20  C 3.45 x 10 -10 mm Hg at 25  C

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 9 of 66 Table 5 – Chemical and Physical Pr operties of Tralopyril Degradates

Degradate Name CL 322,250 (parent compound minus three

fluorines forming a carboxylic acid by hydration) CL 325,195 (Debrominated parent compound with hydration forming a ketone and an ortho hydroxylated trifluoromethyl group) CL 322,248 (Debrominated CL 322,250)

Inert PC Code 619094 619093 NA Chemical Family Pyroles Pyroles Pyroles

Molecular Formula C 11 H 6 Br 1 CL 1 N 2 C 12 H 6 F 3 ClN 2 O 2 C 11 H 7 CLN 2 Molecular Weight g/ml 281.54 302.64 248.67
Molecular Structures:

Log P (Log Kow) 3.72 2 4.17 2 1.68 2
Solubility in water mg/l 5.63 17.95 476
Vapor pressure mm Hg at 25  C 7.62 x 10 -7 3.45 x 10 -9 7.0 x 10 -11

Henry’s Law (m 3 mol -1 ) 5 x 10 -8 7.65 x 10 -11 4.8 x 10 -14
References: EPI Suite 4.1; 1 Values used in Henry’s Law Calculations 2 These EPI-Suite 4.1 values for Log P are questionable because the experimental log P value for parent traloyril with 3 fluorines and 1 bromine was 3.5 (MRID 45673906). The loss of halogens results in compounds that are more water soluble and therefore the log P is expected to be lower because of preferential partitioning into the water phase.



## 1.4 Use/Usage Description

1.4.1 Summary of Registered Uses

A listing of the registered uses of tralopyril is included in Table 6. Tralopyril is registered for use as antifoulant in paint for both recreational and co mmercial vessels in fresh and salt water. There are two technical products that contain 93.2 and 99 percen t tralopyril and seven end use products that contain 2.9 to 7.28 percent tralopyril. One of the end use products contains only tralopyril and the other six end use products also contain zinc pyrithione (ZPT). The products can be applied by brush, roller and airless spraye r. Two or three coats are recommended for best performance.

Some of the tralopyril end use products that c ontain ZPT prohibit airle ss sprayer application by residential (non-commercial) users and require that residential users apply no more than one coat C N

C l

N O H

H O

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Page 10 of 66 within a 24 hour time period. These restricti ons are based on the ZPT RED (not based on tralopyril). All products are antifouling paints registered fo r use on ships hulls and bottoms and are applied using an airless spra y gun system or brush/roller.

Table 6 – Summary of Tralopyril Registered Uses

Use Application Method Amount Ai in Paint Paint Coverage Boats, ships, hull bottom Brush, Roller, Airless Sprayer 2.9 to 7.28 percent 267 to 528 ft 2 /gallon



### 1.4.2 Usage Information

According to the Section Seven Tracking System(SSTS) database, the production volume for tralopyril is less than 20,000 kg per year for the years 2008 to 2011.



## 1.5 Regulatory History
The first product containing tralopyril (E conea®), 4-bromo-2-(4-chlorophenyl)-5- (trifluoromethyl)-1H-pyrrole-3-car bonitrile, was registered in Ma y of 2002 as a technical product with approved uses to formulate a non-copper based antifoulant coating. The first end use product containing tralopyril was re gistered in 2007. There are curr ently 9 end use products with tralopyril as an active ingredient. There ar e currently no outstanding Data Call-In data requirements for this active ingredient. There ar e no products containing this ingredient as an inert ingredient.



### 1.5.1 Recent/Pending Regulatory Actions There are currently products awai ting registration decisions, these products are not anticipated to affect this work plan.



### 1.5.2 Tolerance Information There are no tolerances or exemptions from tolerances for tralopyr il because there are no currently registered uses for this active ingredient associated with food or feed.



## 1.6 Incidents

1.6.1 Human Health The Incident Data System (IDS) of The Office of Pesticide Programs (OPP) of Environmental Protection Agency (EPA) contains reports of incidents from various sources, including registrants, other federal and st ate health and environmental agen cies and individual consumers, submitted to OPP since 1992. As of June 4, 2013, no incidents have been reported in IDS associated with tralopyril us e from 1992 to the present.



### 1.6.2 Ecological No tralopyril ecological incidents have been re ported in the Agency’s Ecological Incident Information System (EISS) for the time period spanning 2005 to 2012.

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# 2 Anticipated Data Needs

Table 7 presents a summary of the data anticipate d as being needed to su pport this registration review.Docket Number EPA-HQ-OPP-2013-0217www.regulations.govPage12of66Table 7 – Studies Anticipated as Needed for the Registration Review of TralopyrilGLNStudy NameTestSubstanceTime Frame(Measured inmonths fromDCI Receipt)Risk Assessment(s)Data Will SupportUse Site(s)TriggeringAnticipated DataRequirementApplicable Exposure ScenariosStudies Anticipated to be Required through the Registration Review DCI875.1200887.1400Outdoor Exposure, DermalOutdoor Exposure, Inhalationtralopyril 36Occupational HandlerResidential HandlerAntifoulant PaintAirless Spray Application by CommercialPaintersBrush/Roller Application by Do it YourselfPainters870.3700Developmental Toxicity(non-rodent species)tralopyril 24 Drinking WaterAntifoulant Paint(Fresh Water Uses)Oral exposures to drinking watercontaminated with tralopyril or itsdegradates.870.3800 Reproductive Toxicitytralopyril24Drinking Water Antifoulant Paint(Fresh Water Uses)Oral exposures to drinking watercontaminated with tralopyril or itsdegradates.870.4100 Chronic Oral Toxicitytralopyril36Drinking Water Antifoulant Paint(Fresh Water Uses)Oral exposures to drinking watercontaminated with tralopyril or itsdegradates.870.4200 Cancer Studytralopyril36Drinking Water Antifoulant Paint(Fresh Water Uses)Oral exposures to drinking watercontaminated with tralopyril or itsdegradates.870.5100In vitroSalmonellatyphimurium ReverseMutation Assaytralopyril12Drinking Water Antifoulant Paint(Fresh Water Uses)Oral exposures to drinking watercontaminated with tralopyril or itsdegradates.850.1075 or850.1400Acute (zebra fish) or Earlylife Stage (rainbow trout)tralopyril 24 EcologicalAntifoulant paint(Fresh water Uses)Exposure of aquatic organisms to tralopyrilor its degradates in surface waterSpecialStudy1Whole sediment; chronicinvertebrates freshwater (2species—1 amphipod and 1chironomid)tralopyril 24 EcologicalAntifoulant paint(Fresh and saltwater uses)Exposure of aquatic organisms to tralopyrilor its degradates in sedimentSpecialStudy2Whole sediment, chronicmarine invertebrate(1 species-amphipod)CL 322,250 24 EcologicalAntifoulant paint(Salt water uses)Exposure of saltwater benthic organisms toits degradates in sediment850.2300 Avian Reproduction tralopryil 24 EcologicalAntifoulant paint(Fresh water uses)Exposure of aquatic organisms to tralopyrilor its degradates in surface waterDocket Number EPA-HQ-OPP-2013-217www.regulations.govPage13of66GLNStudy NameTestSubstanceTime Frame(Measured inmonths fromDCI Receipt)Risk Assessment(s)Data Will SupportUse Site(s)TriggeringAnticipated DataRequirementApplicable Exposure ScenariosSpecialStudy3Leaching from antifoulantpaint in freshwaterEP (monitortralopyrilanddegradates)12Ecological Antifoulant Paint(Fresh Water Uses)Oral exposures to drinking watercontaminated with tralopyril or itsdegradates.Exposure of aquatic organisms to tralopyrilor its degradates in surface water.830.7550 or830.7560 or830.75704Log KowCL 322,250CL 322,248CL 325,19512Ecological Antifoulant Paint(Fresh and saltwater use)Exposure of aquatic organisms to tralopyrildegradates in surface water1Based on log P (Log Kow) of >3, Koc values of 5,571-23,150 ml/g, and a half-life of >10 days.2The anticipated DCI requiring this special study will require the submission of a protocol for review prior to conduct of thestudy.3The registrant has not submitted any dataon leaching of tralopyril and its degradates in freshwater. All submitted leachingdata employed artificial seawater andthe Agency assumes that boats currently in ocean water can betransported and used in freshwater, creating exposure. Leachingdata are anticipated to be neededfor each registered paint.4The EPI-Suite 4.1 values are questionable because the experimental log Pvalue for parent tralopyrilwith 3 fluorines and 1 bromine was 3.5 (MRID 45673906).The loss of halogens to form the degradates results in compounds that are more water soluble than the parent compound, and therefore are more likely to have alower log P value than the parent compound.

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# 3 Human Health Risk Assessment

EPA anticipates the need to revise the existing t oxicological endpoints as pa rt of this registration review. Tables 7 and 8 presents the endpoints us ed in EPA’s most recent human health risk assessments. Several toxicological studies were id entified as data gaps an d as anticipated data needs for registration review ba sed on currently registered us es. All available information including existing toxi cology studies, valid scientific literatur e, and the studies that are expected to be required for registration review will be co nsidered in establishing the endpoints to be used in the registration review risk assessment. Th e following issues regarding these endpoints will also need to be addressed:

 The inhalation exposures were assessed in the initial registrati on decision using an endpoint of 5.7 mg/kg/day that was converted from a 90 day i nhalation toxicity study in rats where the LOAEL was 20 mg/m 3 

### based on portal of entry e ffects. This conversion was made so that the PHED unit exposure da ta, which are reported in terms of exposure per amount of ai handled, could be used. During registration review an inhalation exposure study, where the exposures are reporte d in terms of air c oncentration, will be used and these exposures will be assessed using a human equivalent concentration (HEC). It is estimated th at the HEC would equal 24 mg/m 3 

### using the formula HEC= LOAEL * 6 hours/8 hours * RDDR where the RDDR = 1.57. It also estimated that the level of concern for the uncertainty fact or would be 100 which would include the standard factors of 3 and 10 normally associated with an HEC and an additional factor of 3 for the lack of a NOAEL. Dividing the HEC of 24 mg/m 3 

### by the uncertainty factor of 100 yields an “RfC” of 0.24 mg/m 3 

### as an eight hour TWA. This Rfc value would most likely be used to assess inhalation exposures for occupational handlers.

 Dermal exposures were assessed in the initia l registration decision using an endpoint of 1000 mg/kg/day for systemic effects from a derm al toxicity study. This endpoint will not be used during registration review because de rmal exposures are not normally assessed when the NOAEL is at the limit dose. It will be necessary; however, to the assess irritation effects that are re presented by the NOAEL of 100 mg /kg/day for the appearance of sores that were observed at the LOAEL of 300 mg/kg/day.

Table 8 –Existing Toxicological Endpoints for Dietary Exposure to Tralopyril (Water)

Exposure Scenario Dose Used for Endpoint Uncertainty Factors for Risk Assessment Study and Toxicological Effects

Acute Dietary 6.3 mg/kg/day (LOAEL, Females) 10X intraspecies, 10X intraspecies, 3X conversion of the LOAEL to a NOAEL

Acute RfD = 6.3 mg/kg/day 10 x 10 x 3

= 0.021 mg/kg/day Subchronic (90) Day Oral LOAEL = 6.3 mg/kg/day (LDT) for females based on microscopic findings of the brain and spinal cord. NOAEL could not be determined in the females. LOAEL = 16.2 mg/kg/day in males. NOAEL = 5.2 mg/kg/day

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Exposure Scenario Dose Used for Endpoint Uncertainty Factors for Risk Assessment Study and Toxicological Effects

Chronic Dietary (general population) 6.3 mg/kg/day (LOAEL, Females) 10X intraspecies, 10X intraspecies, 3X conversion of the LOAEL to a NOAEL 10X data base uncertainty (missing chronic study and a neurotoxicity study)

Chronic RfD = 6.3 mg/kg/day 10 x 10 x 10 x 3

= 0.0021 mg/kg/day Subchronic (90) Day Oral LOAEL = 6.3 mg/kg/day (LDT) for females based on microscopic findings of the brain and spinal cord. NOAEL could not be determined in the females. LOAEL = 16.2 mg/kg/day in males. NOAEL = 5.2 mg/kg/day



### Table 9 – Existing Toxicological Endpoints for Occupational/Resid ential Exposure to Tralopyril

Exposure Scenario Dose Used in Risk Assessment Target MOE for Risk Assessment Study and Toxicological Effects Dermal* Short-Term (1-30 days) and Intermediate-Term (1–6 months) NOAEL = 100mg/kg/day Target MOE = 100 (10x interspecies extrapolation, 10x intraspecies variation+. Subchronic (90 Day) Dermal LOAEL = 300 mg/kg/day based on the appearance of

sores

Dermal* Long-Term (6 months – lifetime) Risk assessment was not required based fo r this use pattern because long term exposures are not anticipated.

Inhalation

Short-Term (1-30 days) and Intermediate Term (1 – 6 months) NOAEL could not be calculated (<20mg/m 3 ) (LDT). Target MOE = 300

10x interspecies extrapolation, 10x intraspecies variation, 3x conversion of LOAEL to NOAEL Subchronic (90 Day) Inhalation Toxicity (Phase I)

LOAEL is 20-mg/m 3 based chronic and subacute inflammation, ulcerations, exudates, epithelial hyperplasia,hyperkeratosis and degeneration of the olfactory epithelium in the nasal section N1 to N3. Decreased body weight gain was also seen at this dose level. Inhalation Long-Term (6 months – lifetime) Risk assessment not required based for this use pattern

Cancer No cancer data available *Note - The toxicological end point for dermal systemic effects will not be used for registration review because it was based on a NOAEL of 1000 mg/kg/day which was the highest dose tested.

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## 3.1 Dietary Exposure

3.1.1 Food

There are no food uses for tr alopyril and therefore the EPA doe s not anticipate the need to conduct a dietary (food) risk assessment.



### 3.1.2 Drinking Water The U.S. EPA conducted a drinking water assessment in 2008 and results were summarized in a memorandum dated April 16, 2008 1 

### . The results of both acute and chronic assessments for all subpopulations were below 20% of the aPAD or cPAD. Drinking water exposures to water containing tralopyril residues from the antifouling pa int uses were not cons idered of concern at the time. After reviewing the 2008 risk assessment the Agency has conclude d that it is necessary to update the previous drinking wate r assessment. This is due to advances in the scientific tools and models available to the Agency since c onducting the 2008 assessment. A summary of planned revisions to the drinking wa ter assessment are as follows:

 More recent version of DEEM-FCIDTM: The 2008 memo states that the risk assessment was conducted using the Diet ary Exposure Evaluation Model (DEEMFCIDTM, Version 2.02) DEEM-FCIDTM which us es food and drinking water consumption data from the U.S. Deparent of Agricultu re’s Continuing Surveys of Food Intakes by Individuals (CSFII) for 1994-1996 and 1998. A newer version (3.18) of DEEM-FCIDTM is currently available 2,3 

### that contains more recent f ood commodity consumption data derived from the National Health and Nutrit ion Examination Survey/”What We Eat in America” for 2003-2008 4



### .

 A newer version of MAMPEC (3.0) 5 

### is currently available. The most recent version will be used to estimate refined drinking water residue values.

 Drinking water residue values will be furt her updated based on the development of a freshwater lake scenario in MAMPEC . The 2008 memo states that the drinking water residue estimate used as an input into DEEM-FCIDTM was determined using Version 1.6 of the Marine Antifoulant Model to Predict Environmental Concentrations (MAMPEC) for the primary degradation products of tralopyril, CL 322,250 and CL 322,248. MAMPEC is an integrated hydrodynami c and chemical fate models that provides predictions of environmental concen trations of antifouli ng products in various aquatic environments. The model has trad itionally focused on six “typical” marine environments, which were used in the 2007 ecological risk assessment and 2008 drinking water assessment. However, the Agency is in the process of refini ng a fresh water lake

1 U.S. EPA (United States Environmental Protection Agen cy). 2008. An AD Memo from Talia Lindheimer to Marshall Swindell on “Acute and Chronic Drinki ng Water Exposure and Risk Assessment for the Registration Action of tralopyril (EPA Reg. #2693-200)”, April 16, 2008.
2 http://www.epa.gov/opp00001/science/deem/
3 http://www.epa.gov/oppfead1/cb/csb_page/updates/2012/deem-fcid.hl
4 http://www.cdc.gov/nchs/nhanes.h
5 http://www.deltares.nl/en/software/1039844/mampec/1232321

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 17 of 66 scenario which will allow the Agency to upda te the drinking water residue values as appropriate.

 Availability of freshwater leaching data : due to the development of a fresh water lake scenario in MAMPEC, the Agency expects to refine the MAMPEC model estimations using freshwater leaching data. It has been determined that in order to properly address the potential freshwater risk, leaching data in fresh water are anticip ated to be required for parent tralopyril as well as its two primary degradates (CL 322,250 and CL 322,248). Once received and reviewed, the freshwater l eaching data will be used to estimate refined drinking water residue values.

 Availability of anticipated chronic/cancer study will further allow for a refined drinking water assessment.

The fate properties of tralopyr il used in the drinking water assessment are summarized in a 2008 memorandum 6



### . 

## 3.2 Occupational and Re sidential Exposures
Occupational and residential e xposures are anticipated during the application of tralopyril containing antifoulant paints to commercial vess els and pleasure craft. The Agency assessed these exposures in 2007 prior to the registration of these paints, however, the Agency anticipates the need to revise these assessments because they relied upon use assumptions, unit exposure values and toxicological endpoints that are no longe r valid. These assessments will need to be reassessed using the updated values.



### 3.2.1 Occupational Handler Exposure Occupational handler dermal and inhalation expo sures to tralopyril were assessed for handlers spraying antifoulant pain t products onto ships 7 

### . This assessment was based on a product (Sigma Nexxum 20) which contained 3.4 percent tral opyril and had a cove rage of 220 feet ft 2 

### /gallon at 4 mils dry thickness. The inhalation and dermal exposures were assessed using PHED unit exposure data for the airless sprayer scenario. The inhalation unit exposures were adjusted using protection factors of 10, 50 and 100 for half face air purifying resp irators, full face powered air purifying respirators (PAPR) and full face supplied air respirator s. The dermal unit exposures were adjusted using factor of 2 to account for the use of tyvek coveralls. The amount of paint handled was assumed to be either 14 gallons based on a submitted assessment or 50 gallons based on generic information from the ACC. The dermal MOEs ranged from 87 to 830 and exceeded the target 100 for both use estimates (i.e . 14 or 50 gallons) if gloves were worn. The inhalation MOEs ranged from 7 to 6000 and exceed ed 100 only if the two highest levels of respiratory protection (Full face PAPR or full face SAR) were worn.

6 U.S. EPA (United States Environmental Protection Agen cy). 2008. An AD Memo from James Breithaupt to Marshall Swindell entitled, “Environmental Fate Assessm ent of EconeaTM Technical for New Registration as Antifoulant in Fresh Water”, April 1, 2008.
7 Tralopyril Occupational Exposure Re-Assessment Using a Revised Dermal Toxicity Endpoint: Update of November 15, 2006 Review for a New Active Ingredient, 1H-Pyrrole-3-carbonitrile, 4-bromo-2-(4-chlorophenyl)- 5-(trifluoromethyl) ,(a.k.a., tralopyril ), Proposed as an Antifoulant D295928, D327535, D327536 & D330452, 2/15/2007.

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 18 of 66 The labels generally require dermal ppe (i.e. gl oves) that yield dermal MOEs of 100 but they do not require respiratory protecti on that yields MOEs of 100. So me labels do not require any respiratory protection even though they allow spray application. Some labels only specify that a “mask” should be worn while others have the statement “commercial users must wear a respirator with an organic vapor removing cartri dge with a pre-filter approved for pesticides (MSHA/NIOSH APPROVAL NUMBER TC-14G) or a NIOSH approved full face respirator with an organic removing cartridge with a P- 100 prefilter”. Because the general phrase “a respirator” does not itself specify the type of respirator, a worker could wear a half face respirator which yields an MOE of 60, and still be in compliance with certain labels. It is recommended that the labels be revised to stat e that full face respirators with organic vapor cartridges and P-100 pref ilters are required for spray applications.

The occupational handler exposures listed in Table 9 will need to be reassessed during registration review to account for the following factors that have changed:

 The product assessed at the time of re gistration (11350-GL: Sigma Nexxium 20 Antifouling) had 3.4 percent tralopyril 7 

### . Since that time other products have been registered that have as mu ch as 7.28 percen t tralopyril.

 The assessment was done using PHED unit e xposure data for airless spraying. These data were based on studies where airless spraying of houses was conducted. In 2007, EPA received a worker exposure study of shipyard painting operations. The unit exposures from this study range from 2.7 to 113 ug/m 3 

### per lb ai handled when expressed as an 8 hour time weighted average (TWA) and some are above the PHED unit exposure of 48 ug/m 3 

### /lb ai expressed as an 8 hour TWA.

 The amount of paint handled was assumed in the occupational exposure assessment 7 

### to be either 14 gallonsbased on an observationa l study submitted by the registrant (MRID 468466-02) or 50 gallons based on a standard AD assumption th at had been derived from an industry estimate provided by the Am erican Chemistry Council in 2005. In comparison, the amount handled in the ZPT sh ipyard study ranged from 12 to 83 gallons with an average of 35 gallons.

Table 10 – Occupational Handler Ex posure Scenarios for Tralopyril

Scenario Exposure Route(s) Duration Airless Sprayer Application of Antifoulant Paint In halation Short, Intermediate, and Long Term



### 3.2.2 Residential Handler Exposures

Residential handler dermal a nd inhalation exposures to tr alopyril were assessed for the application of tralopyril antifoulant paint products onto pleasure craft 8 

### . This assessment was

8 Residential Exposure and Risk Assessment of the End Us e Product, Trilux 44 – White Antifoulant Paint, (EPA Reg. No. 2693-220) Containing 3.9% of the Active Ingredient, 1 H-Pyyrole-3-carbonitrile, 4-bromo-2-(4- chlorophenyl)-5-(trifluoremethy l), as an Antifoulant in Paint for Pleasure Craft and Do-it-Yourself Applications, D384689, 4/10/ 2008.

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 19 of 66 based a product (2693-220, Trilux White Antifouling Paint) that contains 3.9 percent tralopyril. The dermal exposures were assessed using PHED unit exposure data for the brush/ roller scenario and the inhalation exposures were a ssessed using data from a literature study 9 

### . The amount of paint handled was based on the hull sizes of 14, 20 and 30 feet, a coverage of 400 ft 2 

### per gallon and one to three coats painted with in a 24 hour period. The dermal MOEs ranged from 360 to 4,300 without gloves and the inha lation MOEs ranged from 2,400 to 21,000 without respiratory protection.

The residential handler dermal exposures listed in Table 10 will need to be reassessed during registration review to account for the following factors that have changed:

 The product assessed at the time of registrati on had 3.9 percent tralopyril. Since that time other products have been registered th at have as much as 7.28 percent tralopyril.

 The dermal exposure assessment will need to be done with a more representative exposure study, MRID 465118-01 which was done on residential yacht painters. The mean dermal unit exposures from this study ar e 312 mg/lb ai with long sleeved shirt, long pants and no gloves and 41 mg/lb ai with l ong sleeved shirt, long pants and gloves. These values are greater than the corres ponding PHED unit exposures for brush/roller applications of 180 mg/lb ai and 24 mg/lb ai.

 Dermal exposures were assessed using an endpoint of 1000 mg/kg/day for systemic effects from a dermal toxicity study. This assessment may need to be repeated to account for the dermal irritation NOAEL of 100 mg/kg/day which is from the same study where sores were observed at a LOAEL of 300 mg/kg/day.

Table 11 – Residential Handler Ex posure Scenarios for tralopyril

Scenario Exposure Route(s) Duration Applying Paint Using Brushes and Rollers Dermal Short Term



### 3.2.3 Residential Post-Application Exposures Because tralopyril is used only as an antifoulant pa int, residential post application exposures are not anticipated.


## 3.3 Aggregate and Cumulative Exposure

3.3.1 Aggregate Exposures Prior to the registration of tr alopyril, assessments were conducte d for dietary exposures from drinking water and for dermal and inhalation expo sures from residential handler application of

9 Potential Exposure of Amateurs (Consumers) through Pa inting Wood Preservative and Antifoulant Preparations. Garrod ANI, Guiver R, Rimmer DA. Annals Occupational Hygiene, Vol. 44, No. 6, pp.421-426. (MRIDs 462444- 21 and 473073-08)

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 20 of 66 paints to pleasure craft; however, an aggr egate assessment was not conducted. Upon a reevaluation and selection of t oxicological endpoints, combined with the updated human health exposure assessments expected as a part of this registration review cas e, aggregate exposures may need to be assessed. This assessment may include dietary (drinki ng water) exposures and residential exposures.



### 3.3.2 Cumulative Exposures With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common me chanism of toxicity, EPA has not made a common mechanism of toxicity finding as to tr alopyril and any other substances and tralopyril does not appear to produce a toxic metabolite pro duced by other substances. For the purposes of this registration review, therefore, EPA has not assumed that tralopyril has a common mechanism of toxicity with other substances . For information regarding EPA’s efforts to determine which chemicals have a common mech anism of toxicity and to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/.


# 4 Environmental Risk Assessment

The Agency conducted an ecological hazard assess ment and environmental risk characterization for tralopyril and its degradates in April of 2007 10 

### as part of the new use registration as an antifoulant. The 2007 risk assessment was not refined and therefore an endangered species effect determination was not made at the tim e of registration. The Agency will conduct a comprehensive updated ecological risk assessmen t for the antifoulant use of tralopyril.

The Agency anticipates needing th e following data in order to c onduct a complete ecological risk assessment for tralopyril, including an endangered species assessment:

 (OPPTS GLN 850.2300) Avian Reproduction

 (OPPTS GLN 850.1075 or 850.1400) Acute Freshwater Fish Toxicity with Zebra fish or Fish Early-Life Stage with Rainbow Trout

 (Special Study) Whole Sediment; Chroni c Invertebrates Freshwater and Marine

 Leaching from antifoulant paint in fresh wate r (EP with monitoring of tralopyril and its major degradates)

 Log Kow (Log P) data for CL 322,250, CL 322,248, and CL 325,195

To fill toxicity data gaps remaining for tralopyril’s major degradates CL322,250 and CL322,248, they will be assumed to be as toxic as the parent compound.

10 U.S. EPA (2007). An AD Memo from Richard Petrie to Marshall Swindell entitled EconeaTM (tralopyril) Antifoulant New Chemical Registration, Ecological Hazard Assessment and Environmental Risk Characterization (PC Code: 119093).

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 21 of 66 The Agency has not conducted a risk assessmen t that supports a complete endangered species determination. The planned update to the ecological risk assessment conducted during registration review will allow th e Agency to determine whether tralopyril’s use has 'no effect' or 'may affect' federally listed threatened or endang ered species (listed species) or their designated critical habitats. If the assessment indicates th at tralopyril (parent and degradates/metabolies) “may affect” a listed species or its designated critic al habitat, the assessment will be refined. A more refined assessment involves clear delineation of the action area associated with proposed use of tralopyril antifoulan t and use of best available informa tion on the temporal and spatial colocation of listed species with respect to the action area. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.



## 4.1 Environmental Fate a nd Exposure Pathways
A previous environmental risk assessment for ecological exposure to freshwater aquatic organisms (MRID 47301601) was submitted and reviewed. The 2007 risk assessment (MRID 47301601) assessed use in fresh water and sea water settings. Three diffe rent aquatic models were used to predict expected environmental con centrations (EEC’s) in harbors, marinas, bays, and channels in U.S. waters; the assessment incl uded application to naval vessels, commercial ships, cruise ships, and pleasure craft. Model runs submitted were reviewed for completeness and accuracy by the Agency. Marine Antif ouling Model to Predict Environmental Concentrations (MAM PEC) Model results, which had the highest EECs (Barbours Point Marina, Houston) were used in the 2007 risk assessment.

Since the 2007 risk assessment, a further revi ew indicates that additional information on environmental fate and ecological toxicity for pa rent tralopyril is needed to assess the risk to endangered and threatened federally listed ( i.e ., listed) species. Fu rther review of the environmental fate studies indicate s that the freshwater leaching ra te used in the assessment was found not to be supported by any data in the Ag ency’s records. All submitted studies on the leaching rate of parent tralopyril and its degradates were for salt water and not fresh water. In addition, an erroneous log Kow (log P) value of 3 for parent tralopyril was reported in place of the correct log Kow value of 3.5 and th e log Kow of the CL 322,250, CL 322,248, and CL 325,195 degradates needs to be submitted . Thes e log Kow values will be used in modeling. Also, the stability of the degradates in sedime nt raises concerns ove r reproductive effects for aquatic benthic invertebrates bu t only subchronic (10-da y) study results are available. The Agency plans to conduct an endangered species risk assessment that a ddresses the lack of leaching data for fresh water, the erroneous and missing log Kow values, and the lack of reproductive data.

Once parent tralopyril is released from the paint matrix into water, it is expected to form the primary and major degradate CL 322,250 (defluorin ated parent compound). Aquatic exposure will be primarily from the CL 322,250 degradate, which is more persistent than parent tralopyril 11 

### . Another major degradate, debrominated CL 322,250 (CL 322,248), is formed under

11 MRIDs 45673908, 45673909, 45673910, 45673911, 45673912

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Page 22 of 66 anaerobic conditions (rep resenting bottom sediment) and in saltwater conditions and did not degrade 12 

### . The study results may be seen in Table 16.

Degradation of parent tralopyril produces co mpounds of different chemical and physical properties. The degradates have lower molecula r weight, higher water so lubility, and lower log Kow (Log P) values. Therefore, they would be expected to be present in water with a higher water:sediment ratio than parent tralopyril. Based on the molecula r weights, vapor pressures, Henry’s Law constants, and study results (MRIDs 45673910, 45673911, 45673912, EPI-Suite 4.1), neither parent tralopyril nor its degradates are expected to volatilize from water ( Table 18).

Parent tralopyril and its degradat es are expected to be present in both the water and sediment compartments in water bodies. Parent tral opyril will continually leach and any organisms present will be exposed to the parent compound a nd its degradates. The exposure in the water column is expected to be higher in marinas with boat storage than in open water because of boat density, the constant presence of sitting boats, an d the lack of water exch ange because of a low flushing rate in some cases. However, the sorp tion based on suspended sediment in marinas is likely to reduce these water concentrations 13 

### . The limited depth in a marina relative to the open water will mean that boat propellers will stir up sediment which will sorb aqueous residues of tralopyril and its degradates.

The registrant has submitted a bioconcentra tion in fish study (M RID 48680501) for parent tralopyril which has not been formally reviewed but will be reviewed in Registration Review. The study reports bioconcentration factors (BCF s) of 3.2-32X (unitless) in carp at acid conditions, which are below the pKa of 7.08. As a result, the tralopyril was not ionized and would have had maximum bioconcentration. The pK a is not likely to change significantly for the major degradates because they retain the nitrile group which carries the pKa. The CL 322,250 degradate was not found based on persistence of parent tralopyril under acid conditions.

A large number of ecotoxicity studies for tralopryil and its degradates were submitted. The deterministic risk assessment used the maximu m expected environmental concentration (EEC) and toxicity endpoints for avian sp ecies, fish, invertebrates, estuarine/marine species, sediment dwelling species, and plants to generate ri sk quotients for the degradates CL 322,250 and CL 322,248 (debrominated CL 322,250). Some limited ecotoxicity studies were submitted for the minor degradate 325,195 (debrominated parent tr alopyril), however the 325,195 degradate is not a concern due to its relatively low rate of formation (< 7.1 % of applied) 14 

### and low toxicity to test species (see Appendix C ). Terr estrial bird, mammal, or plant e xposure is not expected to occur to any great extent for antifoulants because the treated paint stays at or below the water line. However, the risk to waterfowl exposed to tr alopryil and degradates through feeding were assessed based on avian concerns when compounds si milar to tralopryil are used in agricultural fields.

12 MRID 45673910
13 MRIDs 45673913, 45673914
14 MRID 45673910 contained the maximum formation (7.1 % of applied tralopyril) of all environmental fate studies. Degradates formed at <10 % of applied parent compound are considered to be “minor” (5/10/11 memorandum from Don Brady, Environmental Fate and Ef fects Division, Guidance for Determini ng Pesticide Residues of Concern in Drinking Water in Coordination with the HED ROCKS )

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 23 of 66 As an antifoulant, parent tralopyril can leach from treated boat paints and degrades primarily to CL 322,250, defluorinated parent compound, in the environment. Cl 322,250 is more persistent and more mobile than parent tralopyril and will be the primary compound to which aquatic organisms are exposed Because pe sticide residues have the poten tial to reach the habitat of aquatic organisms, it is necessary to determine the risk to aquatic fish, in vertebrates, and plants that may occur from parent tralopyril and its degradates. An ecological conceptual model summarizing exposure pathways for tralopyril and its reaction produc ts/degradates is provided in Figure 1.

In Figure 1 all lines for leaching of parent tralopyril and its meta bolites are solid, indicating that environmental exposure is expected to occu r primarily from parent tralopyril and the degradate/metabolite CL 322,250. The lines representing exposure from down-the-drain exposure leading into wastewater treatment pl ants (WWTPs) are dashed because all paints containing tralopryil are solven t based (not water based) a nd cannot be released into a wastewater treatment plant 15 

### . Exposure to total tralopyril resi dues (parent and degradates) will occur in both water and sediment 16 

### . In addition, the degradate debrominated CL 322,250 (CL 322,248) is expected to be present in anaerob ic (representing sediment) and in saltwater conditions 17



### . The registrant has submitted leaching data from antifoulant paints for parent tralopyril and degradates in salt water, but not from freshwater, and freshwater leaching data are required to assess the potential for effects on Federally-listed species. The Agency assumes that tralopyril can be used to treat freshwater and marine ships and boats, and that treate d boats can be used in both freshwater and saltwater . Leaching of tralopyril (parent and CL 322,250) from 19 antifoulant paints in salt wa ter (Table 19) was observed at maximum rates of 2.2-48 ug/cm 2 

### /day 18 

### . However, the registrant assumed a leaching rate of 4 ug/cm 2 

### /day for the parent compound in freshwater in the risk asse ssments contained in MRIDs 47250101 and 47301601. Based on this assumed parent leaching rate (4 ug/cm 2 

### /day), the registrant-calculated leaching rates for the CL 322,250 and CL 322,248 degradates of 3.84 and 3.456 ug/cm 2 

### /day. These degradate leaching rates were based on the maxi mum percent formation of 96 and 86 % in the environmental fate studies 19 

### . When compared to the actual maximum leaching rates (19 total), the assumed fresh water leaching rate of 4 ug/cm 2 

### /day for parent tralopyril was lower than 18 of the 19 observed maximum rates and lower than 17 of the 19 observed average and minimum rates. Therefore, any predictions of the exte nt of leaching and ecological and drinking water exposure using the 4 ug/cm 2 

### /day value are likely to be underestimates.

15 http://des.nh.gov/organization/commissioner/pip/factsheets/hw/documents/hw-29.pdf
16 MRIDs 45673910, 45673911, 45673912, 45673913, 45673914
17 MRID 45673910
18 MRIDs 48734904, 48734905, 48734906, 48734907, 47500201, 45673201, 46934508, 47238912, 47550801, 47554203, 48297806, and 49046003
19 MRIDs 45673908, 45673909, 47128801, 45673910, 45673911, 45673912, 45673913, 45673914.

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 24 of 66 Figure 1 – Conceptual Model for Ecologi cal Exposure and Effects of Tralopyril to Aquatic Organisms from the Antifoulant Use



## 4.2 Ecological Effects Assessment
The ecological effects assessment evaluates the pot ential for adverse eff ects as a result of tralopyril’s use as an antifoulant. As described in the Agency’s Overview Document (U.S. EPA, 2004), the most sensitive endpoint for each taxa is evaluated. Assessment endpoints include direct toxic effects on the surviv al, reproduction, and growth of te rrestrial and aquatic life, as well as indirect effects, such as reduction in prey base and/or modification of habitat. The evaluated taxa include birds, freshwater and marine/estuarine fish, freshwater and marine/estuarine aquatic inverteb rates, small mammals, benthic fr eshwater and marine/estuarine invertebrates, algae, an d terrestrial plants.

Acute (short-term) and chronic (long-term) toxi city information was characterized based on registrant-submitted studies. A summary of the available ecotoxicity information are provided in this preliminary work plan. Table 12, Table 13, and Table 14 summarize the most sensitive ecological toxicity endpoints based on an ev aluation of the submitted studies.



### 4.2.1 Mode of Action The mode of action is being review ed to determine if a total toxic residue approach will be taken.



### 4.2.2 Measures of Effect (Ecoto xicology Assessment Endpoints) Current selected ecotoxicologica l endpoints are summarized in Table 12, Table 13, and Table 14. A more detailed description of the ecotoxicity studies are provided in Appendix C . Stressor

Source

Receptors and Exposure Routes

Attribute Change(s) Individual organisms Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae Reduction in prey Modification of PCEs related
to prey availability Habitat integrity Reduction in primary productivity Reduced cover Community change Modification of PCEs related to habitat Surface Water/Sediment

Aquatic Animals Invertebrates Vertebrates Exposure Media

Ingestion Ingestion Uptake/gills

or integument

Aquatic Plants
Non

‐ vascular Vascular Uptake or sorption/cell, roots, leaves,

Piscivorous* Invertebrates Vertebrates Phytoplanktivore/ Herbivore Invertebrates Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g ., amphibians, mollusks, crustaceans, etc.) Ingestion Domestic Waste Water Treatment Plant (WWTP)

Key Most likely

exposure pathway contributing to risk
Low likelihood of contributing to risk In

‐ Service Use of Tralopyril in Boat Paints as an Antifoulant

WWTP microorganisms Uptake or sorption

Population Respiration inhibition Down

‐ the

‐ drain disposal of wastewater from rinsing paint rollers, brushes, and trays

Paint Leaching and Removal in Water

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 25 of 66 Table 12 – Selected Effects Endpoints for the Ecological Risk Assess ment of Tralopyril

Receptor Group Surrogate Species Risk Scenario Study Duration Toxicity Endpoint Classification Reference

Terrestrial Animals: Birds Northern Bobwhite ( Colinus virginianus ) Acute Oral 14-Day LD 50 = 24.7;

NOEL = 6 (mg ai/kg-bw) Acceptable MRID 43492809

Mallard Duck ( Anas
p latyrhynchos ) Subacute (Dietary) 10-Day LC 50 = 10.76;

NOEL = 5.62 (mg/kg-diet) Acceptable MRID 46596005

Data Gap: Avian Reproduction

Aquatic Animals: Freshwater Fish Rainbow Trout ( Oncorhynchus mykiss ) Acute 96-Hour LC 50 = 1.3;

NOEC = 0.68 (μg a.i./L) Acceptable MRID 46596002

Chronic 1 Data Gap: Early life stage with Rainbow Trout ( Oncorhynchus mykiss ) or Acute Zebra Fish 1 ( Danio rerio )

Aquatic Animals: Freshwater Invertebrates Water Flea ( Daphnia
magna ) Acute 48-Hour EC 50 = 1.5 μg a.i./L Acceptable MRID 46596001

Chronic 21-Day NOEC = 0.20 μg a.i./L Acceptable MRID 46596004

Aquatic Animals: Marine/Estuarine Fish Sheepshead Minnow ( Cyprinodon variegatus ) Acute 96-Hour LC 50 = 23.71 μg a.i./L Acceptable MRID 45674003
Chronic 34-Day NOEC = 4.3 μg a.i./L Acceptable MRID 45674007

Aquatic Animals: Marine/Estuarine Invertebrates Mysid ( Americamysis bahia ) Acute 96-Hours LC 50 = 0.98 μg a.i./L Acceptable MRID 45674006
Chronic 28-Day NOEC = 2.28 μg/L Acceptable MRID 44911101 Eastern Oyster ( Crassostrea virginica ) Acute (Shell Deposition) 96-Hour EC 50 = 0.64 μg a.i./L Acceptable MRID 46751305
Aquatic Animals: Freshwater Benthic Invertebrates Two species ( Hyalella azteca and Chironomous sp.) Chronic Data Gap: Freshwater benthic invertebrate

Aquatic Animals: Estuarine/Marine Benthic Invertebrates Amphipod ( Leptocheirus
p lumulosus ) Chronic Not Anticipated to be Needed for Parent: In Estuarine/Marine environment the parent is highly unstable, data with stable de gradate are anticipated to be needed

Aquatic Plants: Non-Vascular Marine Diatom ( Skeletonema

costatum ) Non-listed 96-hour IC 50 = 2.7; Acceptable MRID 46619901 Listed 96-hour NOAEC = 1.5 μg/L

Aquatic Plants: Vascular Duckweed ( Lemna gibba) Non-listed 7-day IC 50 = 87.2 μg a.i./L Acceptable MRID 45674116 Listed 7-day NOAEC = 22 μg a.i./L

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Page 26 of 66 Receptor Group Surrogate Species Risk Scenario Study Duration Toxicity Endpoint Classification Reference

Aquatic Rooted Plant Rice ( Oryza sativa ) Seedling Emergence Non-listed 14-day IC 25 = 170 μg a.i./L Acceptable MRID 45674115 Listed 14-day NOAEC > 170 μg a.i./L

Terrestrial Mammal Rat Acute (Oral) N/A LC 50 = Not established— Will use 90-d or similar results for assessing risk 2 Acceptable See Table 15 MRID 45673915

Chronic N/A Not Required

1 Rainbow trout was the most acutely sensitive species tested . Because there can be wide differences in species sensitivity a chronic value is needed for this species so that chronic risk is not underestimated. This anticipated data requirement may be met by either a fi sh early stage chronic value for rainbow trout or a fathead minnow acute value which can be used along with the existing fathead minnow early life stage test to derive an acute-to-chronic ratio (ACR) which can be applied to the rainbow trout acut e value to estimate a rainbow trout chronic value.

2 To asses risk to terrestrial animals ingesting water or f ood contaminated with econea a value from available data will be used as a surrogate.



### Table 13 - Selected Effects E ndpoints for the Ecological Risk Assessment of Tralopyril's Major Degradate CL322,250

Receptor Group Surrogate Species Risk Scenario Study Duration Toxicity Endpoint Classification/ Comments Reference

Terrestrial Animals: Birds Mallard Duck ( Anas
p latyrhynchos ) Subacute (Dietary) 11-Day LC 50 = 962;

NOAEL = 250 (mg/kg diet) Acceptable MRID 46596013

Aquatic Animals: Freshwater Fish Rainbow Trout ( Oncorhynchus mykiss ) Acute 96-Hour LC 50 = 520;

NOAEC= 320 (ppb) Acceptable/ updated from 2007 risk assessment MRID 46596010

Chronic 1 ELS Data Gap: Early life stage with Rainbow Trout ( Oncorhynchus mykiss ) 1

Aquatic Animals: Freshwater Invertebrates Water Flea ( Daphnia magna ) Acute 48-Hour EC 50 = 510;

NOAEC = 250 (ppb) Acceptable MRID 46596008

Chronic 21-Day NOAEC = 300 ppb Acceptable MRID 46596011

Aquatic Animals: Marine/Estuarine Fish Sheepshead Minnow ( Cyprinodon variegatus ) Acute 96-Hour LC 50 > 950; NOEC ≥ 950 (ppb) Supplemental/ For purposes of the risk assessment, the non-definitive LC 50 value will be used as the LC 50 value 2

. MRID 45674101

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Page 27 of 66 Receptor Group Surrogate Species Risk Scenario Study Duration Toxicity Endpoint Classification/ Comments Reference

Chronic 34-Day NOAEC = 240 ppb Acceptable MRID 45674106

Aquatic Animals: Marine/Estuarine Invertebrates Mysid ( Americamysis bahia ) Acute 96-Hour LC 50 = 550;

NOAEC = 330 (ppb) Acceptable MRID 45674104

Chronic 28-Day NOAEC = 82 ppb Acceptable MRID 46596012 Eastern Oyster ( Crassostrea virginica ) Acute (Shell Deposition) 96-Hour EC 50 = 310; NOEC = 46 (ppb) Acceptable MRID 45674103
Aquatic Animals: Freshwater Benthic Invertebrates -- Chronic Not anticipated to be needed. Data from tests with the parent will be used to assess risk to degradate in this case.
Aquatic Animals: Estuarine/Marine Benthic Invertebrates Amphipod ( Leptocheirus
p lumulosus ) Chronic Data anticipated to be required. In seawater parent is not expected to be stable. CL32 2,250 is expected to be the compound present in sediments in seawater given its stability and Kd, Kow. No chronic repr oduction data are available.

Aquatic Plants: Non-Vascular Marine Diatom ( Skeletonema

costatum ) Non-listed 96-hour IC 50 = 660 ppb Acceptable MRID 46596014 Listed 96-hour N OAEC = 500 ppb

Aquatic Plant: Vascular Duckweed ( Lemna gibba) Non-listed 7-day IC 50 > 990 ppb Supplemental— parent value will be used to conduct risk
assessment MRID 45674122 Listed 7-day N OAEC = 530 ppb

Aquatic Rooted Plants Rice ( Oryza sativa ) Seedling
emergence non-listed -- Not anticipated to be needed. Data from tests with the parent will be used to assess risk to degradate in this case. Listed --

Terrestrial Mammals Rat Acute Oral Data Anticipated to Be Required (See Table 1)
Chronic Data Anticipated to Be Required (See Table 1)

1 No fish early life stage (ELS) test with the most acutely sensitive tested species, rainbow trout, is available. A chronic value for the rainbow trout is anticipated to be required. The anticipated data requirement may be met in a number of ways such as submittal of a rainbow trout ELS te st, or submittal of a zebra fish acute study to use in calculating a rainbow trout ch ronic NOAEC using an existing and acceptable zebra fish ELS test and an acute-tochronic ration (ACR) from the zebra fish data, or if no da ta are submitted, data from the parent will be used as a surrogate.

2 Without a definitive acute LC 50 or an acceptable limit test, risks may over estimated.

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 28 of 66 Table 14 - Selected Effects E ndpoints for the Ecological Risk Assessment of Tralopyril's Major Degradate CL322,248

Receptor Group Surrogate Species Risk Scenario Study Duration Toxicity Endpoint Classification Reference

Terrestrial Animals: Birds Mallard Duck ( Anas
p latyrhynchos ) Subacute (Dietary) 8-day LC 50 > 5620; NOEC = 3160 (ppm) Acceptable MRID 46751310

Aquatic Animals: Freshwater Fish Rainbow Trout ( Oncorhynchus mykiss ) Acute 96-hour Data anticipated to be required. Based on available data from other species this degradate appears less toxic than the parent and CL322,250. For the risk assessment for a total toxic residue approach this degradate will be assumed to be as toxic as CL322,250.

Chronic 1 ELS Data anticipated to be required. Based on available data from other species this degradate appears less toxic than the parent and CL322,250. For the risk assessment for a total toxic residue approach this degradate will be assumed to be as toxic as CL322,250.

Aquatic Animals: Freshwater Invertebrates Water Flea ( Daphnia
magna ) Acute 48-hour A supplemental study is available but because of study issues it is not suitable for use in the risk assessment. —Based on available data from other species this degradate appears less toxic than the parent and CL322,250. The CL322,250 value will be used to conduct risk assessment for this degradate.

Chronic 21-day A supplemental study is available but because of study issues it is not suitable for use in the risk assessment. —Based on available data from other species this degradate appears less toxic than the parent and CL322,250. The CL322,250 value will be used to conduct risk assessment for this degradate.

Aquatic Animals: Marine/Estuarine Fish Sheepshead Minnow ( Cyprinodon variegatus ) Acute 96-hour LC 50 > 89,000 ppb Acceptable MRID 46751309

Chronic ELS Data anticipated to be required. Based on available data from other species this degradate appears less toxic than the parent and CL322,250. For the risk assessment for a total toxic residue approach this degradate will be assumed to be as toxic as CL322,250.

Aquatic Animals: Marine/Estuarine Invertebrates Mysid ( Americamysis bahia ) Acute 96-Hour LC 50 = 4300 ppb Acceptable MRID 46751308

Chronic Data anticipated to be required. Based on available data from other species this degradate appears less toxic than the parent and CL322,250. For the risk assessment for a total toxic residue approach this degradate will be assumed to be as toxic as CL322,250.
Aquatic Animals: Freshwater Benthic Invertebrates -- Chronic Data anticipated to be required. Based on available data from other species this degradate appears less toxic than the parent and CL322,250. For the risk assessment for a total toxic residue approach this degradate will be assumed to be as toxic as CL322,250.

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 29 of 66 Receptor Group Surrogate Species Risk Scenario Study Duration Toxicity Endpoint Classification Reference

Aquatic Animals: Estuarine/Marine Benthic Invertebrates -- Chronic Data anticipated to be required. Based on available data from other species this degradate appears less toxic than the parent and CL322,250. For the risk assessment for a total toxic residue approach this degradate will be assumed to be as toxic as CL322,250.

Aquatic Plants: Algae Bluegreen Algae (Anabaena flosaquae ) Non-listed IC 50 > 1000 ppb Supplemental— CL 322,250 values will be used to conduct risk assessment MRID 45893904 Listed NOEC = 1000 ppb

Marine Diatom ( Skeletonema

costatum ) Non-listed IC 50 > 1,200; NOEC = 160 (ppb) Supplemental because did not obtain definitive values—will use this data if EEC values are lower otherwise will use CL322,250 data as surrogate MRID 45674127 Listed NOEC = 160 ppb

Aquatic Plant: Vascular Duckweed ( Lemna gibba) Non-listed IC 50 > 930 ppb Supplemental because did not obtain definitive values—will use this data if EEC values are lower otherwise will use CL322,250 data as surrogate MRID 45674125

Listed NOEC > 930 ppb

Aquatic Rooted Plants Rice ( Oryza sativa ) Seedling
emergence non-listed -- Not anticipated to be needed. Data from tests with the parent will be used to assess risk to degradate in this

case. Listed --

Terrestrial Mammals Rat Acute Oral Data not anticipated to be required
Chronic Data not anticipated to be required



## 4.3 Exposure Analysis Plan

4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates The Agency in 2007 performed an ecological hazar d and risk characteri zation for the use of tralopyril as an antifoulant. For assessment, the Agency used data based on two models which included MAMPEC (Marine Antifoulant Model to Predict Environmental Concentrations) and, EFDC (Environmental Fluid Dynamic Code ). The environmental conditions for Barbours Cut (Houston), Baltimore Harbor (Maryland), and Norfol k Harbor/James River (Virginia) were used as inputs for running these models. The mode l simulations were used to estimate the concentrations of CL322,250 and CL 322,248 in the a bove harbor systems. The outputs from the MAMPEC runs from the Barbours Point (Houston) were used for ecological risk assessment of

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 30 of 66 tralopyril. This assessment was focused on large ships only. The Agency has since developed a fresh water lake scenario for use of antifoulan ts. The Agency will reassess the fresh- and saltwater exposure and risk to non-listed and listed species. Th e potential risk to endangered species was not addressed in previous assessment. To properly address the potential freshwater risk, leaching data in fresh water will be requir ed for parent tralopyril as well as its two primary degradates (CL 322,250, and CL 322,248).


# 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its 2008 reregistrati on decision for tralopyril, EPA reviewed these data and selected the most sensitive endpoints fo r relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), tralopyril is subject to the endocrine screening part of the Endocri ne Disruptor Screeni ng Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 scre en all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide activ e ingredients and 9 inert ingred ients. Tralopyril is not among the group of 58 pesticide active ingredients on th e initial list to be sc reened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call-ins, requiring the submission of EDSP sc reening assays for tralopyril.

For further information on the status of the ED SP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening ba ttery, please visit our website: http://www.epa.gov/endo/.


# 6 Optional Label Changes

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 31 of 66 It is recommended that the labels be revised to indicate that fu ll face respirators with organic vapor removing cartridges a nd P-100 prefilters are require d for spray applications.



# 7 Guidance for Commenters

7.1 Preliminary Work Plan
The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work plan for the tralopyril regi stration review case.



### 7.1.1 Trade Irritants Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. The Agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specifici ty as possible regarding the nature of the

concern.



### 7.1.2 Water Quality Neither parent tralopyril nor its de gradates are identified as a caus e of impairment for pesticidal uses in any water bodies listed as impaired under section 303(d) of the Clean Water Act 20 

### . All sites listed for pesticides , and organics were reviewed and none of them listed tralopyril, CL 322,250, or debrominated CL 322,250 (CL 322,248).

More information on impaired water bodies and TMDLs 21 

### can be found at EPA’s website 22 

### . The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water B ody and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 23 

### in order to ensure they can be used quantitatively or qualitativel y in pesticide risk assessments.



### 7.1.3 Environmental Justice

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, and policies. To help address potential

20 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885
21 TotalMaximum Daily Load (TMDL). TMDL is a calculation of the maximum amount of a pollutant that a waterbody can receive and still safely meet water quality standards (http://water.epa.gov/lawsregs/lawsguidance/cwa/tmdl/index.cfm )
22 h tt p : // w a t e r

. e p a

. g o v / l a w s r e g s / l a w s g u i d a n c e / c w a / t

m d l / i nd e x

. c fm
23 http://www.epa.gov/oppsrrd1/regist ration_review/reg_review_process.htm

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 32 of 66 environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to tralopyril compared to the general population. Please comment if you are aware of any sub-populatio ns that may have atypical, unusually high exposure compared to th e general population.



### 7.1.4 Structure Activity Relationships EPA must rely upon information of appropriate qual ity and reliability for each decision made by the Agency. In the Office of Pesticide Program s (OPP), the evaluation process for a pesticide chemical traditionally begins with the applicant’ s submission of a set of studies conducted with the specific pesticide chemical of interest. The us e of the results of such testing (measured data) is a logical, scientifically rigorous proce ss that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

Today, there is significant interest in alternat ive techniques, i.e., tech niques other than data generation that could significantly inform the Agency’s decision-making process. Recently, OPP has made increasing use of stru cture activity relationship (SAR ) as part of its regulatory decision-making process. In the SAR process, a ch emical's molecular structure is compared to that of other chemicals for which data are availabl e. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties. Thus, the chemical’s physical, chemical, and biol ogical properties are a f unction of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a selected set of measured da ta on a single physical, chemical, or biological property is used to derive a model (an equatio n) to predict the valu e of that property.

Since SAR assessments and QSAR modeling are anothe r set of tools that are available to Agency scientists, OPP has begun a proce ss shift that envisions shifting from the current study-by-study approach to an approach in which the use of pr edicted data, generated us ing validated models, is considered along with information from open litera ture and studies specifically generated under Part 161 requirements. All relevant information w ould be considered as pa rt of a weight-of-theevidence evaluation.

At this time, EPA believes that for certain e ndpoints, especially physi cal/chemical and fate properties, that SAR and QSAR might be effect ively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals. When considering biological prope rties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is appropriate because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a screening-level assessment procedure rather than multiple tiers of assessments with progressively more data requirements.

If stakeholders believe that submission of predic ted data can fulfill one of the data needs for the tralopyril case, then the Agency invites submi ssion of this information. The submitter would be expected to supply a rationale describing th e utility of the information and provide documentation on the scientific va lidity of the information. The de termination that the predicted

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 33 of 66 data fulfills the data requirement would be at the sole discretion of the Agency. Pre-submission consultation with the Agency is encouraged.



### 7.1.5 Additional Information

Stakeholders are also specifically asked to provid e available information a nd data that will assist the Agency in refining its risk assessments, including any species-spec ific ecological effects determinations. The Agency is interested in receiving the following information:

1. Confirmation on the following label information: A. Sites of application B. Formulations C. Application methods and equipment D. Maximum application rates E. Frequency of application, applicatio n intervals and maximum number of applications F. Geographic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non-agricultura l uses (e.g., material s preservation) 5. Typical application interval 6. State or local use restrictions 7. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency 8. Monitoring data



# 8 Next Steps

After the 60-day comment period closes in A ugust 2013, the Agency will review and respond to any comments received in a timely manner, and then issue a Final Work Plan for the tralopyril

case.


# 9 References

Best, S.; McGuire, G. (1999) Identification of Unknown Component Presen t in a Day 30 Surface Water Following Application of (Carbon- 14)-R107894 to Loamy Sand Sediment: Lab Project Number: 17802: 16787: 367605. Unpublis hed study prepared by Inveresk Research. 34 p. 45673912

Cafarella, M. (2005) R107894 - Acute Toxicity to Water Fleas, (Daphni a magna) Under FlowThrough Conditions. Project Number: 13751/6144, AGR/921. Unpublished study prepared by Springborn Smither s Laboratories. 66 p. 46596001.

Cafarella, M. (2005) R107894 - Full Life Cycle Toxi city Test with Water Fleas, Daphnia Magna, Under Flow-Through Conditions. Project Number: 13751/6145, AGR/922. Unpublished study prepared by Springborn Smithers Laboratories. 81 p. 46596004

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 34 of 66 Cafarella, M. (2005) CL322,250 - Acute Toxicity to Water Fleas, (Daphnia Magna) Under Flow Through Conditions. Project Number: 13751/6151, AGR/925. Unpublished study prepared by Springborn Smither s Laboratories. 68 p. 46596008.

Cafarella, M. (2005) CL322,250 - Full Life-Cycle Toxicity Test with Water Fleas, Daphnia magna, Under Flow-Through Conditions . Project Number: 13751/6152, AGR/926. Unpublished study prepared by Springbor n Smithers Laboratories. 81 p. 46596011

Cafarella, M. (2005) CL322,250 - Life Cycle Toxicity Test with Mysids (Americamysis bahia). Project Number: 13751/6153, AGR/927. Unpub lished study prepared by Springborn Smithers Laboratories. 87 p. 46596012

Cafarella, M. (2006) R107894 - Acute Toxicity to Eastern Oyster (Crassostrea virginica) Under Flow-Through Conditions. Proj ect Number: 13751/6157, AGR/1176, TS/FT/OYSTER/R107894. Unpublished study prep ared by Springborn Laboratories Inc. 70 p. 46751305

Cox, P.; Ristorcelli, D. (2001) R107894: Determina tion of the Physico-Chemical Properties (pH, pKa, and EC Tests A4, A6 and A8): Fi nal Report: Lab Project Number: 1073/41-D2141: AGR 00301. Unpublished study prepared by Cova nce Laboratories, Ltd. 59 p. MRID 45673906.

Deltares Software. 2012. MAMPEC 3.0 model. http://www.deltares.nl/e n/software/1039844/mampec/1232321

Dionne, E. (2001) CL322.250--Acute Toxicity to Ea stern Oysters (Crassost rea virginica) Under Flow-Through Conditions: Lab Project Number: 13751.6123: AGR 364: 031301/FIFRA/OPPTS/FT-OYS TER. Unpublished study prepared by Springborn Laboratories, Inc. 71 p. {OPPTS 850.1025} 45674103

Durando, J. (2005) Primary Eye Irritation St udy in Rabbits: R107894. Project Number: P324, 17342. Unpublished study prepared by Produc t Safety Laboratories. 17 p. 46539401

Gallagher, S.; Martin, K.; Beav ers, J. (2005) R107894: A Dietary LC50 Study with the Mallard. Project Number: AGR/916, 168/101B. Unpublished study prepared by Wildlife International, Ltd. 75 p. 46596005

Gallagher, S.; Martin, K.; B eavers, J. (2005) CL322250: A Dietary LC50 Study with the Mallard. Project Number: AGR/1116, 168/102. Unpublished study prepared by Wildlife International, Ltd. 75 p. 46596013

Gallagher, S.; Martin, K.; B eavers, J. (2006) CL322248: A Dietary LC50 Study with the Mallard. Project Number: AGR/1174, 168/103. Unpublished study prepared by Wildlife International, Ltd. 62 p. 46751310

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 35 of 66 Garrod, Ani, R. Guiver, and D.A. Rimmer. Year??? Potential Exposure of Amateurs (Consumers) through Painting Wood Preservativ e and Antifoulant Preparations. Annals Occupation Hygiene, 44(6), pp. 421-426. MRIDs 46244421 and 47307308)

Hall, T.; Donald, E. (2001) R107894 Technical: Ac ute Oral Toxicity (Fix ed Dose Procedure) Test in Rats: Lab Project Number : 19839: 577486. Unpublished study prepared by Inveresk Research. 39 p. {OPPTS 870.1100} 45673915

Hall, T.; Donald, E. (2001) R107894 Technical: Ac ute Dermal Toxicity (LD50) Test in Rats: Lab Project Number: 19836: 577470. Unpublished study prepared by Inveresk Research. 37 p. {OPPTS 870.1200} 45673916

Hawkins, W.; Donald, E. (2002) R107894 Technica l: Buehler Test in Guinea Pigs for Delayed Skin Sensitisation Potential: Lab Pr oject Number: 20973: AGR304: 577512. Unpublished study prepared by Inveresk Research Group. 61 p. 45673919

Hoberg, J. (2001) R107894--Toxicity to Duckweed, Lemna gibba: Lab Project Number: 13751.6104. Unpublished study prepared by Springbor n Laboratories, Inc. 74 p. {OPPTS 850.4400} 45674116

Hoberg, J. (2001) CL322,250--Toxicity to Duck weed, Lemna gibba: Lab Project Number: 13751.6108: AGR 338. Unpublished study prepar ed by LISEC. 70 p. {OPPTS 850.4400} 45674122

Hoberg, J. (2001) CL 322,248--Toxicity to Du ckweed, Lemna gibba: Lab Project Number: 13751.6111: AGR 339. Unpublished study prepared by Springborn Laboratories, Inc. 70 p. {OPPTS 850.4400} 45674125

Hoberg, J. (2003) CL322, 248--Toxicity to the Fres hwater Diatom, Naviculla pelliculosa: Lab Project Number: 13751.6135: AGR 479: EC/OPPTS/SA-NAVICULA. Unpublished study prepared by Springborn Smither s Laboratories. 70 p. {OPPTS 850.5400} 45893904

Hoberg, J. (2005) R107894- Acute T oxicity to the Marine Diatom , Skeletonema costatum, Under Static Conditions. Project Number: 1 3751/6147, AGR/1026. Unpublished study prepared by Springborn Smithers Laboratories. 69 p. 46619901

Hoberg, J. (2005) CL322,250 - Acute Toxicity to the Marine Diatom, Skeletonema costatum, Under Static Conditions. Project Nu mber: 13751/6154, AGR/1027. Unpublished study prepared by Springborn Smither s Laboratories. 70 p. 46596014

Hutchinson, A.; Donald, E. (2002) R107894 Technical : Acute Dermal Irritation Test in Rabbits: Lab Project Number: 20682: AGR 306: 577491. Unpublished study prepared by Inveresk Research. 38 p. {OPPTS 870.2500} 45673918

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Page 36 of 66 Knox III, D. (2011) Econea Technical: Preliminary Analysis. Project Number: 32442, AGR/4539, P809. Unpublished study prepared by Eurofins/Product Safety Laboratories. 84p. 48596802

Koga, Y. (2011) Bioconcentration Study of R107 894 in Carp: Final Report. Project Number: 642/10/S/5626, 45626, AGR/4535. Unpublished study prepared by Chemicals Evaluation and Research Institute. 81p. 48680501

Lentz, N. (2007) Non-GPL Photolysis of R107894 and CL332,250 in Sterile pH 5 Buffer and Non-GLP Indirect Photolysis of R107894 in Sterile Synthetic Humic Water (SHW). Project Number: 13751/6162. Unpublished study prepared by Springborn Smithers Laboratories. 45 p. 47128801

Lima, W. (2001) R107894--Acute Toxicity to Sheepshead Minnow (Cyprinodon variegatus) Under Flow-Through Conditions: Lab Project Number: 13751.6119: AGR 368. Unpublished study prepared by Springborn Laboratories, Inc. 65 p. {OPPTS 850.1075} 45674003

Lima, W. (2001) R107894--Acute Toxicity to Mysids (Americamysis bahia) Under FlowThrough Conditions: Lab Project Number: 13751.6118: AGR 371. Unpublished study prepared by Springborn Laboratorie s, Inc. 64 p. {OPPTS 850.1035} 45674006

Lima, W. (2001) CL 322.250--Acute Toxicity to Sheepshead Minnow (Cyprinodon variegatus) Under Flow-Through Conditions: Lab Project Number: 13751.6122: AGR 367: 020499/FIFRA/OPPTS/FT-SHM. Unpublishe d study prepared by Springborn Laboratories, Inc. 62 p. {OPPTS 850.1075} 45674101

Mackie, J. (1997) Determination of the Hydr olytic Stability of (Carbon-14)-RC107894: Lab Project Number: 390042: 15348. Unpublished study prepared by Inveresk Research. 105 p. 45673908

Mackie, J. (1998) Adsorption/Desorption of (Carbon-14)-R107894 in Sediments: Lab Project Number: 390723: 15715. Unpublished study prepar ed by Inveresk Research. 122 p. 45673913

Mackie, J. (1999) Adsorption/Desorption of th e Hydrolysis Products of (Carbon-14)-R107894 in Sediments: Lab Project Number: 16693: 390770. Unpublished study prepared by Inveresk Research. 123 p. 45673914

Mackie, J. (1999) The Aerobic Degradation of (Carbon-14)-R107894 in Two Water/Sediment Systems: Lab Project Number: 393001: 16787. Unpublished study prepared by Inveresk Research. 97 p. 45673911

Mackie, J. (2000) The Anaerobic Degradation of (Carbon-14)-R107894 in Two Water/Sediment Systems: Lab Project Number: 17832: 393017. Unpublished study prepared by Inveresk Research. 102 p. 45673910

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 37 of 66 Millen, W. (2001) Validation of HRGC Method M-3467.01 to Assay for CL 312264 and CL 322,697 in the Technical Grade of AC 303268: Lab Project Number: APBR 1153: 00- APBR-1125-9. Unpublished study prepared by BASF. 53 p. {OPPTS 830.1700}. MRID 45673903

Milligan, F.; Williams, S.; McGuire, G. (1997) Supplement to Hydrolytic Stability Report NO 15348: Identification of Hydr olytic Degradation Products of (Carbon-14)-R107894: Lab Project Number: 15365: 364871: 15348. Unpublis hed study prepared by Inveresk Research. 37 p. 45673909

Moore, G. (2006) Acute Inhalation Toxicity Study in Rats - Limit Test: R107894. Project Number: 19437, AGR/1269, P330. Unpublished st udy prepared by Product Safety Laboratories. 22 p. 46846601

Putt, A. (2001) CL 322,250--Acute Toxicity to Mysids (Americamysi s bahia) Under FlowThrough Conditions: Lab Project Number: 13751.6121: AGR 370. Unpublished study prepared by Springborn Laboratorie s, Inc. 62 p. {OPPTS 850.1035} 45674104

Putt, A. (2005) R107894 - Acute Toxicity to Rainbow Trout (Oncorhynchus mykiss) Under Flow-Through Conditions. Project Nu mber: 13751/6143, AGR/920. Unpublished study prepared by Springborn Smither s Laboratories. 67 p. 46596002

Putt, A. (2005) CL322,250 - Acute Toxicity to Rainbow Trout (Onchorynchus mykiss) Under Flow-Through Conditions. Project Nu mber: 13751/6150, AGR/924. Unpublished study prepared by Springborn Smither s Laboratories. 69 p. 46596010

Ristorcelli, D. (2001) R107894: Determination of the Physico- Chemical Properties: Final Report: Lab Project Number: 1073/48-D 2149: AGR 00351. Unpublished study prepared by Covance Laboratories, Ltd. 65 p. MRID 45673907

Sayers, L. (2006) CL322,248 - Acute Toxicity to Sheepshead Minnow (Cyprinodon variegatus) under Static Conditions. Proj ect Number: 13751/6159, AGR/1178, PPTS/SHM/STA/JANSSEN. Unpublished st udy prepared by Springborn Laboratories Inc. 60 p. 46751309

Sayers, L. (2006) CL322,248 - Acute Toxicity to Mysids (Americamysis bahia) under Static Conditions. Project Number: 13751/6 160, AGR/1179, PTS/MYSID/ST/JANSSEN. Unpublished study prepared by Sprin gborn Laboratories Inc. 62 p. 46751308

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 38 of 66 Serak, K.; Hanh, J. (2006) Determination of the Leach Rate of Econea fr om Paint (International Copper Free) in Synthetic Seawater. Project Number: 49702, 49702/7. Unpublished study prepared by Analytical Bio-Ch emistry Labs., Inc. 62 p. 46934508

Serak, K. (2007) Determination of the Leach Ra te of Organic Biocides from Two Paints in Substitute Ocean Water: Seaguard HMF 1 and Seaguard HMF 2: HMC Antifouling Paint. Project Number: 49912, 49912/1. Unpublished study prepared by ABC Laboratories, Inc. 125 p. 47238912

Sinning, D. (2002) Leach Rate Determination of Sigma Nexxium 20 Paint Containing Sea Nine 211 and AFO28 Antifoulings: Lab Project Number: 630-16. Unpublished study prepared by Case Consulting Laboratories, Inc. 34 p. 45673201

Sinning, D. (2008) Release Rate Determination of Tralopyril from Smart Solution. Project Number: 3990/01. Unpublished study prepared by Case Consulting Laboratories, Inc. 27 p. 47500201

Sinning, D. (2011) Leach Rate Determination of Pettit Hydrocoat ECO Antifouling Pain 1104 White: Final Report. Project Number: 390/100. Unpublished study prepared by Case Consulting Laboratories, Inc. 34p. 48734904

Sinning, D. (2011) Leach Rate Determination of Pettit Hydrocoat EC O Antifouling Paint 1204 Blue: Final Report. Project Number: 390/101. Unpublished study prepared by Case Consulting Laboratories, Inc. 34p. 48734905

Sinning, D. (2011) Leach Rate Determination of Pettit Hydrocoat EC O Antifouling Paint 1604 Red: Final Report. Project Number: 3 90/102. Unpublished study prepared by Case Consulting Laboratories, Inc. 34p. 48734906

Sinning, D. (2011) Leach Rate Determination of Pettit Hydrocoat ECO Antifouling Pain 1804 Black: Final Report. Project Number: 390/103. Unpublished study prepared by Case Consulting Laboratories, Inc. 34p. 48734907

Sinning, D. (2012) Leach Rate and VOC Determin ation of Armor Solventbase Antifouling Paint: Final Report. Project Number: 260/10. Unpub lished study prepared by Case Consulting Laboratories, Inc. 37p. 49046003

Sousa, J. (2001) R107894--Early Life-Stage Toxicity Test with Sheepshead Minnow (Cyprinodon variegatus): Lab Proj ect Number: 13751.6128: AGR 383. Unpublished study prepared by Springborn Laboratories, Inc. 84 p. 45674007

Sousa, J. (2001) CL 322,250--Early Life-Sta ge Toxicity Test with Sheepshead Minnow (Cyprinodon variegatus): Lab Proj ect Number: 13751.6129: AGR 385. Unpublished study prepared by Springborn Laboratories, Inc. 83 p. 45674106

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 39 of 66 Teixeira, D. (2001) R107894--Determination of Effects on Seedling Emergence of Rice (Oryza sativa): Lab Project Number: 13751.6127: AGR 362. Unpublished study prepared by Springborn Laboratories, In c. 75 p. {OPPTS 850.4100, 850.4225} 45674115

Tunink, A. (2008) Determination of the Leach Rate of Organic Biocides from Four Paint Colors, Code No. LAg 2007 025 - Black, Red, Blue, and Green in Substitute Ocean Water. Project Number: 63315, AGR/3766, ASTM/D/6903/ 07. Unpublished study prepared by ABC Laboratories, Inc. 98 p. 47550801

Tunink, A. (2008) Determination of the Leach Ra te of Organic Biocides from Three Paint Colors, Code No. LAg 2007 023 - Black, White, and Red, in Substitute Ocean Water. Project Number: 63311, AGR/3764, ASTM/D/6903/ 07. Unpublished study prepared by ABC Laboratories, Inc. 90 p. 47554203

Tunink, A. (2010) Determination of the Leach Ra te of Organic Biocide at Three Different Temperatures from the Antifouling Paint Code No. Lag 2008 036 - Blue, in Substitute Ocean Water. Project Number: 65299, AGR /4345. Unpublished study prepared by ABC Laboratories, Inc. 86 p. 48297806

Tutorvista.com. 2013. Van der Waals Equation. http://chemi stry.tutorvista.com/physicalchemistry/van-der-waals-equation.html

U.S. Center for Disease Control. 2013. Nati onal Health and Nutrition Examination Survey (NHANES). http://www.cdc.gov/nchs/nhanes.htm

U.S.Environmental Protection Agency. 1996. OPPTS 850.1730 Fish BCF. EPA 712–C–96– 129. http://www.epa.gov/ocspp/pubs/frs/publica tions/OPPTS_Harmonized/850_Ecological_Ef fects_Test_Guidelines/Drafts/850-1730.pdf

U.S. Environmental Protection Agency (E PA). 2002. ECOTOX User Guide: ECOTOXicology Database System. Version 3.0. Availabl e: http://www.epa.gov/ecotox/

U.S. Environmental Protection Agency. 2007. An AD Memo from Richard Petrie to Marshall Swindell entitled Econea TM 

### (tralopyril) Antifoulant New Chemical Registration, Ecological Hazard Assessment and Environm ental Risk Characterization (PC Code 119093)

U.S. Environmental Protection Agency (EPA). February 15, 2007. Tralopyril Occupational Exposure Re-Assessment Using a Revised Dermal Toxicity Endpoint: Update of November 15, 2006 Review for a New Active Ingredient, 1H-Pyrrole-3-carbonitrile, 4- bromo-2-(4-chlorophenyl)-5-(trifluoromethyl) ,(a.k.a., tralopyril ), Proposed as an Antifoulant D295928, D327535, D327536 & D330452.

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Page 40 of 66 U.S. Environmental Protection Agency. 2008. An AD Memo from Talia Lindheimer to Marshall Swindell on “Acute and Chronic Drinking Wa ter Exposure and Risk Assessment for the Registration Action of tralopyril (E PA Reg. #2693-200)”, April 16, 2008.

U.S. Environmental Protection Agency. Ap ril 10, 2008. Residential Exposure and Risk Assessment of the End Use Product, Trilux 44 – White Antifoulant Pa int, (EPA Reg. No. 2693-220) Containing 3.9% of the Active I ngredient, 1 H-Pyyrole-3-carbonitrile, 4- bromo-2-(4-chlorophenyl)-5-(tri fluoremethyl), as an Antif oulant in Paint for Pleasure Craft and Do-it-Yourself Applications, D384689.

U.S. Environmental Protection Agency. Ma y 10, 2011. Environmental Fate and Effects Division Guidance, Author, Don Brady. Guidan ce for Determining Pesticide Residues of Concern in Drinking Water in Coor dination with the HED ROCKS.

U.S. Environmental Protection Agency. 2012. DEEM-FCID/Calendex Version 3.18/9.14 Release. http://www.epa.gov/pesticides/science/deem/

U.S. Environmental Protection Agency. 2012. EPI-Suite 4.1. http://www.epa.gov/opptintr/exposu re/pubs/episuitedl.htm

U.S. Environmental Protection Agency. D ecember 2012. Registration Review Process. http://www.epa.gov/oppsrrd1/registrati on_review/reg_review_process.htm

U.S. Environmental Protection Agency. 2013. Endocrine Disruptor Screening Program. http://www.epa.gov/endo/

U.S. Environmental Protection Agency (EPA ). 2013. High Production Volume Information System (HPVIS). http://www.epa.gov/hpvis/

U.S. Environmental Protection Agency. 2013. Impaired Waters 303(d) Listings. http://water.epa.gov/lawsregs/law sguidance/cwa/tmdl/listing.cfm

Van der Kerken, K. (2002) Alga, Growth Inhibi tion Test Effect of CL 322,248 on the Growth of Skeletonema costatum: Final Report: La b Project Number: AGR 00309: WE-06-272: KV-2001-10532-R-MJ-WE06272. Unpublished study pr epared by LISEC. 78 p. {OPPTS 850.5400} 45674127

Williams, W.; Northcott, W.; Marincic, K. (2007) Environmental and Ecological Risk Assessment of ECONEA Anti-Foulant Agent in Freshwater Environm ents: Final Report. Project Number: WEI/567/01/F, JANSSEN/ AGR/3762. Unpublished study prepared by Waterborne Environmental, Inc. (WEI). 28 p. 47301601

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Page 41 of 66 Yang, H. (2000) Validation of the Ion Chro matographic Method M-3417.01 to Assay for Triethylamine (TEA) in the CL 303268 Techni cal Grade Active Ingredient (TGAI): Lab Project Number: APBR 1130: 00-APBR-1125-3. Unpublished study prepared by BASF. 49 p. {OPPTS 830.1700}. MRID 45673902.

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Page 42 of 66 

# Appendix A Toxicology Profile

Acute Toxicity for Product Labeling

As summarized in Table 1, in acute toxicity stud ies, tralopyril has been shown to have severe toxicity by the oral route (Toxici ty Category I), moderate toxici ty by inhalation route (Toxicity Category II) and weak toxicity through dermal r oute (Toxicity category III). Tralopyril is a mild skin irritant (Toxicity Category IV ) and a mild eye irritant (Toxicit y Category III). Tralopyril is not a dermal sensitizer.

Table 15 - Acute Toxicity Data for tralopyril

Guideline No. Data Requirement/ Species Conclusions/Acceptable/ Comments Tox Cat MRID

870.1100 Acute Oral/Rat LD 50 = Not established [Acceptable/-Guideline] I 45673915

870.1200 Acute Dermal/Rabbit LD 50 >2000 mg/kg for both males and females [Acceptable/Guideline] III 45673916

870.1300 Acute Inhalation/Rat* LC50 = <510 mg/m 3 (males) LC50 = <510 mg/m 3 (females) LC50 = <510 mg/m 3 (males and females) [Acceptable/Guideline] II 46846601

870.2500 Dermal Irritation/ Rabbit Mildly irritating based on very slight erythematic, but no edema at 72 hours [Acceptable/Guideline] IV 45673918

870.2400 Primary Eye Irritation./Rabbit Mildly irritating [Acceptable/Guideline] III 46539401

870.2600 Dermal Sensitization/ Guinea Pig Not a dermal sensitizer [Acceptable/Guideline] N/A 45673919



## Subchronic Toxicity

The subchronic toxicology database includes a 90 -day oral study in rats, a 28-day dermal rangefinding study in rats, a 90-day rat dermal study in rats, and a 90-day rat inhalation study (with neurotoxicity battery measured) in rats. A summ ary of these studies is included below and more detailed information can be found in the data evaluation records:

90-Day Oral Toxicity Study (MRID 46442201 and MRID 46659701)

This study was evaluated in D323129 of 06/ 29/06 under TXR #1,003,062 and it was found to be acceptable under the relevant guideline (OPPT S 870.3100). During this study tralopyril (94.6% a.i) was administered to 10 Sprague-Dawley ra ts/sex/dose via food at dose levels of 0, 80, 250, or 750 ppm active ingredient. These concentr ations were equivalent to 5.2, 16.2, or 51.9

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Page 43 of 66 mg/kg/day, respectively, in males and 6.3, 20.9, or 62.0 mg/kg/day, respectively, in females. An additional study was performed with 10 Sprague-Daw ley rats/sex/dose at the same concentration as above with 5 rats/sex/dose were undergoing terminal sacrifice by in situ perfusion after anesthesia after 3 months of exposure and 5 rats /sex/dose undergoing a 4-week recovery period. The intake of test article in th ese rats was similar to that obser ved in the main study animals (i.e., 5.1, 16.2, or 51.6 mg/kg/day, respectively, in males and 6.8, 20.7, or 61.4 mg/kg/day, respectively, in females).

No unscheduled deaths occurred during the cour se of the study. There were no treatment - related clinical signs of toxicity, ophthalmological findings, ur inalysis, or macroscopic findings. Food consumption decreased in the first week of treatment in both males and females administered 750 ppm. The body weight gains were low throughout the study, likely due to low food consumption.

Hematology data indicated only minor (<10% di fference from controls) effects in high-dose animals, except for a 15% increas e in platelets in the males w ith a corresponding increase in females that was not significant (9%). All hema tological values were comparable to controls after the 4-week recovery period. Alanine am inotransferase (ALT) and alkaline phosphatase (ALP) were statistically-significantly increased in the mid- and high-dose males, which correlate to increased relative liver weight s in the main group. Females disp layed a lesser increase in ALP with only the high-dose group demo nstrating a statistic ally significant change. Low-dose males also displayed a statistically significant increase in ALP. Signs of dehydration and undernourishment were evident wi th statistically significant increases in phosphorus, urea, magnesium, and cholesterol; and a statistically significant decrease in glucose in high-dose males and females.

Clinical chemistry findings in the recovery gr oup indicate reversibil ity of the effects. Differences in creatinine and triglycerides were generally <10% different from the main control group and were thus considered due to biological variation.

Terminal body weight was reduced a statistically significant amount in mid- and high-dose males and high-dose females, which affected the absolute and/or relative weight s of several organs. treatment-related changes includ e increases in relative brain we ights (mid- and high-dose males; high-dose females) and liver weights (mid- and hi gh-dose males; all treate d females). However, the changes in ALP and ALT enzyme were reversib le after 4 weeks and the increases in the liver were likely due to increased metabolism of the te st article. The relative brain weights in the high-dose animals remained elevated after the recovery period, though the males were the only statistically significant value. However, frank effect s were noted in the brai n at necropsy in these recovery group animals.

Microscopic findings of the brai n and spinal cord observed in the main group were as follows: minimal to moderate multifocal vacuolation of the brain in the mid- and high-dose males and females as well as the low-dose females; modera te to marked multifocal vacuolation of the thoracic cord in the high-dose females; minimal to marked multifocal vacuolation of the lumbar cord in the mid- and high-dose males and fe males as well as the low-dose females.

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Page 44 of 66 Microscopic finding of the brain and spinal cord of the animal s that were in the perfusion fixation satellite group displayed treatment-rela ted finding which included slight to moderate vacuolization. The lumbar region (cauda equina ) was most profoundly aff ected and the females appeared to be more sensitive.

Other treatment-related microsc opic findings in the main group were minimal to slight mucosal hyperplasia of the duodenum in the mid- and high- dose males and females that were reversible after 4 weeks. These were spongiform myelinopa thy in the central and the proximal peripheral nervous system. The most severe lesions were multifocal vacuolation of the white matter and intramyelinic vacuolation of the peripheral nerves in the cauda equina (lumbar cord and root fibers). Peer review of the pathology confir med the general findings, although there were some minor differences on severity and in some instan ces the involvement of vacuolation in several tissues.

There were no changes in behavior or parasy mpathetic movements (e.g. tremors, convulsions, impaired gait, posture, response to handling, activit y, or arousal).

After 4 weeks of no treatment, mi croscopic lesions were still obs erved in the brain and lumbar region. Minimal multifocal vacuolization of the br ain in high-dose males and minimal to slight multifocal vacuolization of the brain in mid- and high-dose females were observed; minimal to slight multifocal vacuolization of the lumbar in mid- and high-dose males and minimal to moderate multifocal vacuolization of the lumbar in all treated females. The lesion severity increased with dose.

The LOAEL is 16.2 mg/kg/day in males based on reduced body weight and body weight gain, reduced food consumption, hematol ogy, clinical chemistry, organ weights, and microscopic findings of the brain and spinal cord. The LOAEL is 6.3 mg/kg/day in females based on microscopic findings of the brain a nd spinal cord. The NOAEL is 5.2 mg/kg/day in males and could not be determined in females.

28-day Rat Range-Finding Dermal Toxicity Study (MRID 466597-02)

This study was evaluated in D323129 of 01/ 31/06 under TXR #1,003,056 and it was found to be acceptable under the relevant guideline (OPPT S 870.3200). During this study, tralopyril (94.6% a.i.) was administered to 5 rats/dose /sex at dose levels of 0, 30, 100, 300, or 1000 mg/kg/day for 29 days (6 hours/day, 5 days/week). Results from this study were used to determine the dose range of a proposed 90-day dermal subchroni c study. Treatment-rela ted effects at 1000 mg/kg/day included ano-genital staining but this was not considered to be toxicologically significant. There were no mortal ities during this study. Additio nally, there were no significant changes to body weight, food consumption, food e fficiency, organ weight, or pathology (gross or microscopic). The LOAEL is >1000 mg/kg/d ay (HDT). The NOAEL is < 1000 mg/kg/day. Based on these results, rats were be expected to tolerate an ex posure of >1000 mg/kg/day in the subsequent 90-day dermal study.

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Page 45 of 66 90-day Rat Dermal Toxicity Study (MRID 46802201, MRID 47006601)

This study was evaluated in D328778 of 06/ 29/06 under TXR #1,003,062 and it was found to be acceptable under the relevant guideline (OPPTS 870.3250, OECD 411). During this study, tralopyril (94.6%) was applied to the shaved skin of 10 rats per sex and dose at doses of 0, 100, 300, or 1000 mg/kg/day, 6 hours/day for 5 da ys/week during a 90-day period. One 100- mg/kg/day female died prior to study terminati on. A treatment-related dose-dependent increase in small dermal sores was noted in both th e mid- and high-dose group. Consequently, the dermal NOAEL is 100 mg/kg/day; a dermal LOAEL is 300 mg/kg/day based on the appearance of sores. There were no other adverse findings with this substance.

The systemic NOAEL is > 1000 mg/kg/day (HDT). The systemic LOAEL is >1000 mg/kg/day.

90-day Rat Inhalation Study with Neurotoxicity Battery (MRID 46802202)

This study was evaluated in D328778 of 06/ 29/06 under TXR #1,003,062 and it was found to be acceptable under the relevant guideli nes (OPPTS 870.3465, 870.6200). During this study tralopyril (92.4% a.i.) was administered via nos e-only exposure to 10 Sprague Dawley rats per sex and air concentration in Phase I and 12 rats pe r sex and air concentrati on in Phase II. The air concentrations (both nominal and an alytical) were 0, 20, 40, and 80 mg/m 3 

### . The exposure period was 6 hours per day, 7 days per week for a minimu m of 90 consecutive days. The particle size was within the accepted range.

The No Observable Adverse Effect Level (NOAEL) was 20 mg/m 3 

### for survival, hematology, clinical chemistry, or gross pathology. Na sal lesions were observed in the 20 mg/m 3 

### animals and were considered a local effect.

One female rat in the Phase I inhalation toxic ity was found dead on study Day 9. This animal was in the control group, therefor e the death was not considered te st article-related. Three males in the 80-mg/m 3 

### Phase II neurotoxicity study group were found dead on study Days 0, 20, and 85, respectively. Additionally, an 80 mg/m 3 

### female in the Phase II neurotoxicity study group was found dead on Day 0 after the first exposure. Since there were numerous deaths in the 80 mg/m 3 

### group these deaths were consid ered test article-related.

Clinical signs of toxicity rela ted to treatment included brown staining on multiple body surfaces in males and females of all three test articl e-treated groups. Staini ng, which began on Day 11 and persisted through the end of the study, was ob served on the neck, forelimb, abdominal area, thoracic area, inguinal area, hindlimb, rump, anog enital area, urogenital area, and tail. Reduced mean body weights for the male and female an imals of the 20- (males), 40-, and 80-mg/m 3 

### test groups were statistically significan tly lower than the control group.

Microscopic treatment related effects were limited to the nose of all of the treated animals. The effects were observed to be loca lized in the dorsal region of th e nose, and included inflammation, ulceration or erosion, squamous or respiratory me taplasia, and olfactory or respiratory epithelial degeneration. These changes disp layed a dose-related increase in incidence a nd severity.

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Page 46 of 66 In the Phase I of the study, the LOAEL was 20 mg/m 3 

### for male and female is 20 mg/m 3 

### based on the findings observed in the N1 (N asal section 1) for both sexes a nd N3 section in the females of the 20-mg/m 3 

### animals. The 20-mg/m 3 

### males exhibited chronic and subacute inflammation, ulcerations (N1), and exudate (N1), and the fema les had subacute inflam mation (N1), epithelial hyperplasia (N1), hyperkeratosis (N1), and dege neration of olfactory epithelium (N3) and decrease body weight gain in male. The NOAE L could not be determined (<20 mg/m3)(LDT).

In the phase II of the study, neurobehavioral as sessment (functional observational battery [FOB] and motor activity testing) was performed on all Phase II animals (12 rats/sex /group) prior to dose administration (pretest), and at Weeks 3, 7, and 12. Cholinesterase activity was not determined. At study termination, 6 animal s/sex/dose in the controls and 80-mg/m 3 

### groups were perfused in situ for neuropathological examinati on of the central and peripheral nervous system tissues. For the Phase II neurot oxicity study, after the first day of exposure, 1 male and 1 female were found dead in the 80 mg/m 3 

### group and were replaced. Two 80 mg/m 3 

### males died prior to study termination, one on Day 20 and the other on Day 85.

During FOB handling measurement, the 40 and 80 mg/m 3 

### animals were observed to have soiled fur, unclean fur, and increased grooming (80 mg/m 3 

### males) during Weeks 7 and 12. These changes correlate with the clinical toxicity findi ngs of soiled fur and were not considered adverse neurotoxicological findings. Du ring Week 3 FOB measurements, an overall decrease in total locomotor activity was noted in the 40 and 80 mg/m 3 

### males and in ambulatory activities for 80 mg/m 3 

### males as a result of reduced activity in sub-session measur ements. During Week 12, the 80 mg/m 3 

### males were observed with total activit y decrease compared to controls.

At neuropathology, an increase in minimal axona l degeneration was observed in the peroneal nerve in the 80 mg/m 3 

### animals (3/6 for both males and females) over controls (0/0 for both males and females).

The neurotoxicity LOAEL was 40 mg/m 3 

### in males based on decreased motor activity and 80 mg/m 3 

### in females based on axonal degeneration ob served in the peroneal nerve. The neurotoxicity NOAEL was 20 mg/m 3 

### for males and 40 mg/m 3 

### for females. 

## Developmental Toxicity

There is one rat developmental study in the tral opyril toxicology database . Since drinking water exposure can occur if tralopyril anti foulant paints are used on fresh water boats or ships, an additional developmental toxic ity study on a second species ( i.e . non-rodent) is anticipated to be needed for registration review.

Rat Developmental Toxicity (MRID 46426902)

This study was evaluated and it was found to be acceptable under the relevant guideline for a developmental toxicity study in rats (O PPTS 870.3700; OECD 414). During this study, tralopyril (94.6% a.i.) was administered to 25 ti me-mated Sprague-Dawley female rats /dose by gavage at dose levels of 0, 5, 10 or 20 mg /kg/day from day 6 through 19 of gestation ( i.e . gd 6- 19).

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Page 47 of 66 Treatment related maternal effects at 20 mg/ kg/day included increase d mortality, frequent salivation, reduced body weight ga in, decreased uterin e weight, decreased corrected body weight gain, increased resorptions (total, early and late) and decreased placental weight. At 10 mg/kg/day, dams exhibited freque nted salivation. The matern al LOAEL is 10 mg/kg/day, based on frequent salivation. Th e NOAEL is 5 mg/kg/day.

Developmental findings also o ccurred at 10 and 20 mg/kg/day. Tr eatment-related effects at 20 mg/kg/day included decreased mean fetal weight a nd an increased incidence of fetuses exhibiting disturbances and delays of o ssification (non/incomplete/dumbbell /biparte) of various skeletal structures (skull, sternebrae), as well as supernumerary (14th) and wavy ribs. The ossification delays were considered to be secondary to matern al toxicity and correlat ed with decreased fetal weight. At 10 mg/kg/day, there was a decrease in mean fetal weight. The developmental LOAEL is 10 mg/kg/day, based on decreased feta l weight, the developmental NOAEL is 5 mg/kg/day. 

## Reproductive Toxicity

There are no reproductive studies in the tralopyril toxicology database. Since drinking water exposure can occur if tralopyril an tifoulant paints are used on fresh water boats or ships, a reproductive toxicity study is anticipated to be needed for registration review. 

## Chronic Toxicity and Carcinogenicity

There are no chronic toxicity studies in the toxicology database. Since drinking water exposure can occur if tralopyril antifoulant paints are used on fresh water boats or ships, chronic toxicity and cancer studies are anticipated to be needed for registration review. 

## Mutagenicity

There are two mutagenicity studies in the toxicology database:

1. In vitro Mammalian Cell Gene Mutation 2. In vivo Mammalian Cell Cytogenetics (B one Marrow Micronucleus),

There is no in vitro Salmonella typhimurium Revers e Mutation Assay in the toxicology database and is considered as a data gap to eval uate the mutagenic pot ential of tralopyril.

In vitro Mammalian Cell Gene Mutation Assay (MRID 46426903),

Chinese hamster ovary (CHO) cells were exposed to tralopyril (94%) in di methylsulfoxide up to cytotoxic and insolubility concentrations and was not mutagenic in the presence or absence of S9 activation. The positive controls did induce the appropriate res ponse. There was no evidence of a concentration-related, positive re sponse that induced mutant colonies over background. This study is classified as ACCEPTABLE-GUIDELINE and satisfies the gu ideline requirement (OPPTS 870.5300, OECD 476) for in vitro mutagenicity (mammalian forward gene mutation) data.

In vivo Mammalian Cell Cytogenetics Assay (MRID 46426904)

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Page 48 of 66 Five 5 male mice per dose were exposed once by or al gavage to tralopyril (>94% pure) in olive oil at doses of 0, 3, 6, or 12 mg/kg bw. Bone marrow cells were harvested at 24 hours posttreatment. There was no mortality among the anim als tested in the main assay, however, clinical signs of toxicity (squatting pos ture) were observed in the 12 mg /kg bw animals at both 24- and 48-hour harvest times. No statistically-signifi cant increases in the number of small or large micronucleated PCEs or NCEs were reported at any dose or harvest time compared to the concurrent solvent control. Additionally, positive controls also showed a significant increase in the percentage of micronucleated PCEs in males; therefore, the positive c ontrol elicited a clearly positive response. There was no significant in crease in the frequency of micronucleated polychromatic erythrocytes in bone marrow after a ny treatment time. This study is classified as ACCEPTABLE-GUIDELINE and satisfies the gui deline requirement (OPPTS 870.5395; OECD 474) for in vivo cytogenetic mutagenicity data. 

## Other Toxicological Effects

There are neurotoxicity effects that have been observed in several submitted studies

1. In the 90-day rat oral study (MRID 46442201 and MRID 46659701), microscopic findings of the brain and sp inal cord were observed in the main group as follows: minimal to moderate multifocal vacuolation of the brain in the mid- and high-dose males and females as well as the low-dose females. These were spongiform myelinopathy in the central and the proximal peripheral nervous system. The most severe lesions were multifocal vacuolation of the white matter and intramyelinic vacuolation of the peripheral nerves in the cauda equina (lumbar cord and r oot fibers). After 4 weeks of no treatment, microscopic lesions were still observe d in the brain and lumbar region.

2. Decreased motor activity and axonal degenerati on in the peroneal nerve were observed in the 90-day rat inhalation study (MRID 46802202).

3. Frequent salivation was identif ied as a significant effect in the rat developmental study (MRID 46426902).

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Page 49 of 66 

# Appendix B Environmental Fate

Parent tralopyril and its degrad ation products can create enviro nmental exposure in water bodies where treated boats either reside or are in use. This is the only registered use of tralopyril, and therefore, exposure in terrestrial situations wi ll not be assessed in th is document. Aquatic exposure will be highest in marinas and around doc ks where boats are stored, and lower outside marinas where boat density is lower. and ther efore long-term acute a nd chronic exposure to aquatic organisms inhabiting these areas will present. In other areas where boats are present and in use ( e.g . areas outside marinas), water exposure will be lower because of lower boat density.

Parent tralopyril degrades by both abiotic processes including hydrolysis 24 

### and photodegradation in water, 25 

### and by biotic processes 26 

### to form CL 322,250, which is defluorinated parent compound with a carboxylic acid group. Hydrolysis half-lives fo r parent tralopyril ranged from 14-175 days at pH 5 to 0.1-0.6 days in pH 9 and seawater. CL 322,250 did not degrade in the hydrolysis study. The photodegradation in water half-lives were 1 day (distilled water and humic acid water) for parent tralopyril and 0.025 days (36 minutes) for CL 322,250. However, the photodegradation in water study has not been fo rmally reviewed and w ill be in registration review. Aquatic exposure in freshwater will o ccur from the parent compound and the more persistent CL 322,250 degradate under acid to neut ral conditions. Under al kaline freshwater and in saltwater conditions, the prim ary exposure will be from the CL 322,250 degradate. The halflives for parent tralopyril in anaerobic condi tions were 29 and 0.7 days in freshwater and saltwater, and were 12 and 0.6 days under aer obic conditions. The half-lives for CL 322,250 were 23-31 days in these conditi ons and were longer than for pa rent tralopyril. Another major degradate, debrominated CL 322,250 (CL 322,248) , is formed under anaerobic conditions (representing sediment) and in saltwater conditions and did not degrade (Table 16).

Degradation of parent tralopyril produces co mpounds of different chemical and physical properties. The degradates have lower molecula r weight, higher water so lubility, and lower log Kow (Log P) values 27 

### . Therefore, the degradates would be expected to be present in water with a higher water:sediment ratio th an parent tralopyril. Based on the molecular weights, vapor pressures, Henry’s Law constants, and study results 28 

### , neither parent tralopyril nor its degradates are expected to vol atilize from water (Table 18).

Sorption to sediment is a significant route of dissipation (disappearance) for tralopyril and its degradates/metabolites. For parent tralopyr il and CL 322,250, the whole sediment sorption coefficients (Kf values) ranged from 22-446 and 14-357 ml/g, respectively. The Koc values for parent tralopyril and CL 322,250 ranged from 3,143-20,273 and 4,571-23,150 ml/g, respectively. For parent tralopyril, the sorpti on for the freshwater and saltwat er sediments was 96-98 and 82-

24 MRIDs 45673908, 45673909
25 MRID 47128801
26 Aquatic metabolism, MRIDs 45673910, 45673911, 45673912
27 The Log P values in Table 18 for the degradates are questionable because the EPI-Suite 4.1 model predicts higher water solubility than parent compound. The 830.7550 test (log P) involves shaking a pesticide in a mixture of octanol and water and more water soluble compounds will tend to partition to water, lowe ring the predicted log P.
28 MRIDs 45673910, 45673911, 45673912, EPI-Suite 4.1

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Page 50 of 66 97 %, respectively. For CL 322,250, the sorption fo r the freshwater and saltwater sediments was 96-98 and 57-95 %, respectively 29 

### . However, the total sorption to sediment in the aquatic metabolism studies 30 

### did not exceed 70 %. In the anaerobic aquatic metabolism study 31 

### , the total sorption (extractable plus unext ractable residues) was 70 and 37 % for the freshwater and salt water systems, respectively. In the aerobic aquatic metabolism study, 32 

### the total sorption (extractable plus unextractable residues) was 42 and 21 % for the freshwater and salt water systems, respectively.

The apparent difference in sorption can be expl ained by the water to sediment ratios in the studies, the use of shaking in the leaching-adso rption-desorption studies (standard practice), and degradation to other compounds. In th e leaching-adsorption-desorption studies 33 

### , the ratio of water to sediment was 5:1. The study design for leaching-adsorption-desorption does not allow for degradation of the tested compound. However, the ratio of water to sediment in the aquatic metabolism studies 34 

### was 10:1. The main reasons for the apparent differences in study results lies in the fact that a lower water: sediment ra tio forces higher sorpti on of a pesticide to the sediment 35 

### . Shaking of the water and sediment in the leaching-adsorption-desorption study (OCSPP 835.1230) to achieve sorption is also standa rd, while shaking is not used in metabolism studies because the shaking can e nhance degradation over the long-term 36 

### . Also, the degradation in the aquatic metabolism studies formed compo unds that are more polar because of loss of halogen molecules (fluorine, bromine) 37 

### . As a result, further degradation of the parent compound and CL 322,250 results in more water so lubility (based on EP I-Suite 4.1) and lower sorption (Table 17 and Table 18). The Koc valu es (sorption to soil expressed as % organic carbon) estimated using EPI-Suite 4.1 were 2,314 and 27-34 ml/g for the minor degradate CL 325,195 (debrominated parent) and major degradate CL 322,248 (debrominated 322,250), respectively (Table 17). In the aquatic metabolism studies 38 

### , the applied parent tralopyril degraded to CL 322,250, CL 322,248 , and CL 325,195 degradates which lose halogens and are sorbed to a lesser degree than parent compounds.

Leaching from antifoulant paints was also observed at up to 2.2-48 ug/cm 2 

### /day. Average and cumulative leaching rates ranged from 1.3-22 ug/cm 2 

### /day and 55.5-986 ug/cm 2 

### , respectively (Table 19).

Bioconcentration in fish and a quatic invertebrates is also po ssible. There was a submitted bioconcentration in fish study 39 

### for parent tralopyril in carp that indicates limited bioconcentration factors (BCFs) of 3.2-32 depending on the treatme nt concentration. However, that study has not been formally reviewed and no c onclusions can be drawn at this time. It will be reviewed in registration review.

29 MRIDs 45673913, 45673914, Table 16
30 MRIDs 45673910, 45673911, 45673912
31 MRID 45673910
32 MRIDs 45673911, 45673912
33 MRIDs 456734913, 45673914
34 MRIDs 45673910, 45673911, 45673912
35 835.1230 test guideline, http://www.regulations. gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0006
36 OCSPP 835.4300 and 835.4400
37 http://chemistry.tutorvista.com/physical-chemistry/van-der-waals-equation.html
38 MRIDs 45673910, 45673911, 45673912
39 OCSPP 850.1730, MRID 48680501

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Page 51 of 66 Table 16 - Summary of parent tral opyril half-lives and degradat e amounts and half-lives in environmental fate studies

Study Type MRID Parent Half-lives (days) Maximum formation % based on applied parent compound 1,2 and half-life CL 322,250 (%) 3 CL 325,195 -(%) 4 CL 322,248 (%) 5

Hydrolysis (835.2120) 45673908 (main study)

45673909 (degradate identification study) 10 o C - Linear half-lives of 175, 2.9, 0.6, and 0.6 days in pH 5, 7, and 9 water fresh and seawater (pH 8), respectively 25 o C- Linear half-lives of 14, 0.4, 0.1, and 0.1 days in pH 5, 7, and 9 water fresh and seawater (pH 8), respectively Distilled water
9.4-96.2 %

(30 d) 1,2 (no half-life calculated--

stable) 6 1.4-4.6 % (30 d) 1 Minor degradate 7 Degradate not formed in the study

Seawater 95.7-96.3 % (1-4 d), 95.2-95.5 %

(30 d) 1,2 (no half-life calculated--

stable) 6 2.7-2.8 % (0.5 d) Minor degradate 7 Degradate not formed in the study

Aqueous Photolysis (835.2240) 47128801 25 o C - Non-linear half-lives of 1 and 0.9 days in distilled water and synthetic humic water (synthetic humic water represents natural water containing humic acid, a natural contaminant) Distilled water 75 % (0 d), <1 % by 5 d 1,2

(half-life of 0.025 days, irradiated) Dark control stable Degradate not formed in the study Degradate not formed in the study (no half-life calculated--stable) 6

Synthetic Humic Water No degradates analyzed No degradates analyzed No degradates analyzed Anaerobic Aquatic Metabolism (835.4300) 45673910 Freshwater system (21 o C) - Non-linear half-life of 29 d 54 % (14 d), 7.2 % (364 d) 1,2 (half-life of 31 days) 1.2 % (364 d) 1 Minor degradate 7 35.7 % (364 d) 1

Saltwater system (21 o C) -Nonlinear half-life of 0.7 d 25 % (7 d) (half-life of 22 days) 7.1 % (3 d), 0.8 % (364 d) 1 Minor degradate 7 19.9 % (273 d), 18.2 % (364 d) 1,2

(no half-life calculated--stable) 6
Aerobic Aquatic Metabolism (835.4400) 45673911 45673912 Freshwater system (21 o C) - Non-linear half-life of 12 d 76 % (7 d), 38 % (30 d) 1,2 (half-life of 25 days) 0.38 % (15 d), <LOQ (30 d) 1 Minor degradate 7 Degradate not formed in the study

Saltwater system (21 o C) -Nonlinear half-life of 0.6 d 36-47 % (21-30 d) 1,2 (half-life of 23 days) 1.9% (30 d) 1 30.3 % (30 d) 1,2

1 End of study period.

2 Numbers in red indicate significant percentages of applied compound.

3 CL 322,250 is parent tralopyril minus three fluorine molecules

4 CL 325,195 is debrominated parent tralopyril

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Page 52 of 66 5 CL 322,248 is debrominated CL 322,250

6 Half-life not calculated because compo und did not degrade in the study and therefore the compound is assumed to be stable

7 Half-life not calculated because compound formed at <10 % of applied parent in the study.



### Table 17 - Sorption (Kf/Koc) of paren t tralopyril and its main degradates
Compound

Parent tralopyril CL 322,250 CL 325,195 Debrominated CL 322,250 (CL 322,248) Kf (Koc) 1 Freshwater

349-446 ml/g (Kf) 17,450-20,273 ml/g (Koc)

Seawater

22-183 ml/g (Kf) 3,143-5,229 ml/g (Koc)

MRID 45673913 Freshwater

189-357 ml/g (Kf) 21,818-23,150 ml/g (Koc)

Seawater

14-119 ml/g (Kf) 4,571-6,743 ml/g (Koc)

MRID 45673914 2,314 ml/g Epi-Suite 4.1 No Kf data available 27-34 ml/g (Koc) Epi-Suite 4.1 No Kf data available

1 Kf is the Freundlich adsorption coefficient for whole sediment. Koc is the Kf/% organic carbon.



### Table 18 - Physical-Chemical Properties fo r Tralopyril and its Primary Metabolites

Compound Molecular weight (g/mol) Water Solubility

(mg/l) Log P (Log Kow) Disassociation constant

(pKa) Vapor Pressure (mm Hg) Henry’s Law (a m 3

mol -1 ) Reference

tralopyril 349.54 0.17 1 (fresh water, pH 4.9)

0.16 (seawater, pH 8.1) 3.5 7.08 at 26 o C 1.42 x 10 -10 at 20  C 1
3.45 x 10 -10 at 25  C 3.8 x 10 -10 Table 4 above

CL 322,250 281.54 5.63 3.72 2 None 7.62 x 10 -7 5 x 10 -8 EPI-Suite 4.1 CL 325,195 302.64 17.95 4.17 2 None 3.45 x 10 -9 7.65 x 10 -11 EPI-Suite 4.1 CL 322,248 (Debrominated CL 322,250) 248.67 476 1.68 2 None 7.0 x 10 -11 4.8 x 10 -14 EPI-Suite 4.1

1 Values used in Henry’s Law Calculations.
2 The EPI-Suite 4.1 values are qu estionable because the experimental log P value for parent traloyril with 3 fluorines and 1 bromine was 3.5 (MRID 45673906). The loss of halogens to form the degradates results in compounds that are likely to have a lower log P value because they are more water soluble. The EPI-Suite 4.1 program predicts higher water solubilities for the dehalogenated degradates, and the log P study design in 830.7550 re quires the shaking of a flask containing n-octanol, distille d water, and the pesticide of interest. Water-soluble pesticides will preferentially partition to water instead of octanol becau se of increased hydrogen bonding.

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Page 53 of 66 Table 19 – Reviewed and Accepted Paint Leac hing Studies for Tralopyril in Seawater

MRID Paint Ingredients (% w/w) Temp ( o C) CL 322,250 40 measured? Review Date Results Maximum, Minimum, an d Average Units are ug/cm 2 /day and Cumulative Units are ug/cm 2 ) 48734904 Petit Hydrocoat ECO Antifouling Paint 1104 White Tralopyril, 6% Zn pyrithione , 4.8% 25 Yes 4/25/12 Rate Maximum Minimum Average Average Cumulative Cumulative Value 48 14 30 21 381 881 Time Interval 1 day 42 days 1-14 days 1-45 days 1-14 days 1-45 days
48734905 Petit Hydrocoat ECO Antifouling Paint 1204 Blue Tralopyril, 6 % Zn pyrithione, 4.8% 25 Yes 4/25/12 Rate Maximum Minimum Average Average Cumulative Cumulative Value 48 10 36 20 351 842 Time Interval 1 day 45 days 1-10 days 1-45 days 1-10 days 1-45 days
48734906 Petit Hydrocoat ECO Antifouling Paint 1604 RED Tralopyril, 6 % Zn pyrithione, 4.8% 25 Yes 4/25/12 Rate Maximum Minimum Average Average Cumulative Cumulative Value 45 8 34 18 325 782 Time Interval 1 day 45 days 1-10 days 1-45 days 1-10 days 1-45 days 48734907 Petit Hydrocoat ECO Antifouling Paint 1804 Black Tralopyril, 6 % Zn pyrithione , 4.8 25 Yes 4/25/12

Rate Maximum Minimum Average Average Cumulative Cumulative Value 31 12 24 17 232 706 Time Interval 1 day 45 days 1-10 days 1-45 days 1-10 days 1-45 days

47500201 Smart Solution Tralopyril, 2.9% 25 Yes 11/13/08

Rate Maximum Minimum Average Average Cumulative Cumulative Value 44 10.3 34.4 20.9 452 850 Time Interval 1 day 45 days 1-14 days 1-45 days 1-14 days 1-45 days

40 All parent tralopyril residues were ch emically converted to the degradate CL 322,250 in the studies for chemical analysis.

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Page 54 of 66

MRID Paint Ingredients (% w/w) Temp ( o C) CL 322,250 40 measured? Review Date Results Maximum, Minimum, an d Average Units are ug/cm 2 /day and Cumulative Units are ug/cm 2 ) 45673201 Sigma Nexxium 20 Paint (Red-Brown) Tralopyril, 3.68% RH-5287, 3.43% 25 Yes 1/6/05 Rate Value Time Interval Maximum 20.8 3 days Minimum 6.0 14 days Average 13.3 1-14 days Average 10.6 14-45 days Cumulative 188 1-14 days Cumulative 454 14-45 days 46934508 International Copper-Free Paint Tralopyril, 3.9 % RH-5287, 4.12 % 25 Yes 1/11/07 Rate Value Time Interval Maximum 7.0 31 days Minimum 4.15 77 days Average 5.9 1-14 days Average 5.8 1-91 days Cumulative 82.2 1-14 days Cumulative 512 1-91 days 47238912 HMF Antifouling Paint I Tralopyril, 7.28% Zn pyrithione,6.38% Yes 1/10/08 Rate Value Time Interval Maximum 13.5 31 days Minimum 6.8 77 days Average 9.2 1-14 days Average 10.3 1-91 days Cumulative 127 1-14 days Cumulative 912 1-91 days 47550801 Lag 2007 025, Black Paint Tralopyril, 3.9% Zn pyrithione, 4.12% 25 Yes 1/8/09 Rate Value Time Interval Maximum 17.9 14 days Minimum 6.7 1 day Average 13.7 1-14 days Average 14.6 1-45 days Cumulative 194 1-14 days Cumulative 678 1-45 days 47550801 Lag 2007 025, Red Paint Tralopyril, 3.9 % Zn pyrithione, 4.12% 25 Yes 1/8/09 Rate Value Time Interval Maximum 19 7 days Minimum 5.4 1 day Average 14.2 1-14 days Average 15.9 1-45 days Cumulative 206 1-14 days Cumulative 751 1-45 days 47550801 Lag 2007 025, Blue Paint Tralopyril, 3.9% Zn pyrithione , 4.12 % 25 Yes 1/8/09 Rate Value Time Interval Maximum 18.4 14 days Minimum 5.7 1 day Average 13.3 1-14 days Average 14.4 1-45 days Cumulative 186 1-14 days Cumulative 670 14-45 days

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Page 55 of 66

MRID Paint Ingredients (% w/w) Temp ( o C) CL 322,250 40 measured? Review Date Results Maximum, Minimum, an d Average Units are ug/cm 2 /day and Cumulative Units are ug/cm 2 ) 47550801 Lag 2007 025, Green Paint Tralopyril, 3.9 % Zn pyrithione, 4.12% 25 Yes 1/8/09 Rate Value Time Interval Maximum 21.2 21 days Minimum 5.1 1 day Average 13.9 1-14 days Average 16.7 1-45 days Cumulative 206 1-14 days Cumulative 801 14-45 days 47554203 Lag 2007 023, Black Paint Percent active ingredients not stated 25 Yes 1/8/09 Rate Value Time Interval Maximum 13 45 days Minimum 8.1 3 days Average 9.9 1-10 days Average 9.9 1-71 days Cumulative 136 1-10 days Cumulative 713 1-71 days 47554203 Lag 2007 023, Red Paint Percent active ingredients not stated 25 Yes 1/8/09 Rate Value Time Interval Maximum 10.8 21 days Minimum 8.6 1 day Average 9.5 1-10 days Average 9.7 1-71 days Cumulative 89 1-10 days Cumulative 695 1-71 days 47554203 Lag 2007 023, White Paint Percent active ingredients not stated 25 Yes 1/8/09 Rate Value Time Interval Maximum 8.5 10 days Minimum 5.0 71 days Average 7.5 1-10 days Average 6.5 10-71 days Cumulative 159 1-10 days Cumulative 474 10-71 days 48297806 Shelter Island Plus Deep Blue Paint (Lag 2008 036 Blue Paint)

Tralopyril, 5.92 % Zn pyrithione, 4.15% 5 Yes 3/1/11

Rate Maximum Minimum Average Average Cumulative Cumulative Value 2.2 0.4 1.0 1.3 12.8 55.5 Time Interval 45 days 7 days 1-14 days 1-45 days 1-14 days 1-45 days 48297806 Shelter Island Plus Deep Blue Paint (Lag 2008 036 Blue Paint) Tralopyril, 5.92% Zn pyrithione, 4.15% 15 Yes 3/1/11 Rate Value Time Interval Maximum 5.3 45 days Minimum 1.7 1 day

Average 2.6 1-14 days

Average 3.3 1-45 days

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Page 56 of 66

MRID Paint Ingredients (% w/w) Temp ( o C) CL 322,250 40 measured? Review Date Results Maximum, Minimum, an d Average Units are ug/cm 2 /day and Cumulative Units are ug/cm 2 ) Cumulative 35.4 1-14 days

Cumulative 149 1-45 days

48297806 Shelter Island Plus Deep Blue Paint (Lag 2008 036 Blue Paint Tralopyril, 5.92 % Zn pyrithione, 4.15% 25 Yes 3/1/11 Rate Value Time Interval Maximum 17.7 45 days Minimum 4.7 1 day Average 7.8 1-14 days Average 11.0 1-45 days Cumulative 108 1-14 days Cumulative 492 1-45 days
49046003 1 Armor SolventBased Antifouling Paint Tralopyril, 5.6 % Zn pyrithione, 4 % 25 Yes N/A Rate Value Time Interval Maximum 34.5 3 days Minimum 12.9 45 day Average 28.6 1-14 days Average 22.0 1-45 days Cumulative 390 1-14 days Cumulative 986 1-45 days

1 MRID 49046003 was has not been formally reviewed but will be reviewed in Registration Review

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Page 57 of 66 

# Appendix C Ecotoxicology Profile Toxicity to Terrestrial Receptors

Birds, Acute and Subacute—Parent and Degradates

For antifoulant coatings and paints, an acute oral toxicity study with a waterfowl and an upland game bird using the technical gr ade of the active ingredient (TGA I) is anticipated to be required to establish the toxicity of a pesticide to birds. This information is used to determine label hazard statements, as well as to estimate risk fo r pesticides which could be directly ingested by birds. Acute oral data for both a waterfowl and an upland game bird have been submitted to the agency. Results of this test are tabulated in Table 20. These results indicate that tralopryil technical is moderately to highly toxic to avian species on an acute oral basis. All avian acute oral data requirements are fulfilled for the parent.

Avian acute oral testing was also conducte d on the CL325,195 metabolite of tralopryil. The results of testing are provided in Table 20. These results indicate that the CL325,195 degradate is slightly toxic to practically non-tox ic to birds on an acute oral basis.

Two subacute dietary studies usi ng the technical grade of the activ e ingredient are anticipated to be required to establish the toxicity of a pesticide to birds, if the use of the pesticide is expected to result in exposure to birds via food items. The preferred te st species are mallard duck (a waterfowl) and bobwhite quail (an upland gamebird). Avian di etary testing with waterfowl was required for tralopyril technical and the two majo r aquatic degradates in order to address the toxicity of the compounds to waterfowl, which may be exposed through feeding or ingestion of water in waters containing tralopyril or its degradates. Results of the submitted avian subacute dietary tests are provided in Table 20. These results indicat e that CL322,250 is highly toxic to waterfowl when ingested via f ood items. All avian subacute da ta requirements are fulfilled for the parent and its two major degradates (CL322,250 and CL322,248).

Birds, Chronic

Avian reproduction studies using th e technical grade of the active i ngredient are anticipated to be required for tralopyril because the following cond itions are met: (1) birds may be subject to repeated or continuous exposure to the pesticid e, especially preceding or during the breeding season, (2) the pesticide is stable in the environment to the exte nt that potentially toxic amounts may persist in animal feed which also includes inge stion of water, and (3) the pesticide is stored or accumulated in plant or animal tissues (indicated by a K ow 

### value of greater than 1000). Avian reproduction testing is required for the currently proposed uses of tralopyril.

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Page 58 of 66 Table 20. Toxicity Profile of Tralop yril Parent and Degradates to Birds

Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

Econea technical 46596005 Mallard Duck ( Anas platyrhynchos ) 11 D LC 50 = 10.76 ppm NOAEL = 5.62 ppm Acceptable

Econea technical 43492809 Northern Bobwhite ( Colinus virginianu s) 14 D LD 50 = 24.7; NOAEL = 6 (mg ai/kg-bw) Acceptable

Econea technical 43492808 Mallard Duck ( Anas platyrhynchos ) 14 D LD 50 = 77 NOAEL = 20 (mg ai/kg-bw) Acceptable

CL 322,250 46596013 Mallard Duck ( Anas platyrhynchos ) 11 D LC 50 = 962 ppm NOAEL = 250 ppm Acceptable

CL 322,248 46751310 Mallard Duck ( Anas platyrhynchos ) 8 D LC 50 > 5620 ppm NOAEL = 3160 ppm Acceptable

CL 325,195 44452612 Mallard Duck ( Anas platyrhynchos ) 14 D LD 50 > 2250 NOAEL > 2250

(mg ai/kg-bw) Acceptable

CL 325,195 44452611 Northern Bobwhite ( Colinus virginianu s) 14 D LD 50 > 741 NOAEL = 192 (mg ai/kg-bw) Acceptable



### Mammals

Wild mammal testing is required on a case-by-case basis, depending on the results of lower tier laboratory mammalian studies, intended use pa ttern and pertinent environmental fate characteristics. In most cases, rat or mouse toxi city values obtained fr om studies conducted to support data requirements for human health risk assessment substitute for wild mammal testing. The Agency uses LC 50 

### values from acute oral mammalian studies and NOEC values from 2- generation reproduction studies al ong with other mammalian data which may be used for risk characterization (e.g. dermal studies). These toxicity values are re ported in Table 15. 

## Toxicity to Freshwater Aquatic Receptors

Freshwater Fish, Acute—Parent and Degradates

Two freshwater fish, one warm water species and one cold water species, toxicity studies using the technical grade of the active ingredient (TGAI) are anticipated to be required to establish the toxicity of tralopyril to fish. This information is used to determine label hazard statements, as well as to estimate risk to freshwater fish from the proposed use. The preferred test species are rainbow trout (a coldwater fish) and bluegill sunfish (a warmwater fish). Results for the parent, tralopyril, are tabulated in Table 21. These results indicate that tr alopryil is very highly toxic to freshwater fish on an acute basis. All acute freshwater fish data requirements have been fulfilled for the parent.

### Docket Number EPA-HQ-OPP-2013-217 www.regulations.gov

Page 59 of 66 Based on the patterns of toxicity seen in marine/est uarine fish acute tests, and in freshwater fish chronic tests, the degradates of concern are less toxic than parent tralopryil. Freshwater fish acute toxicity tests with several tralopryil de gradates were submitted, however, those studies were determined to be invalid a nd are therefore are not included. Freshwater fish acute toxicity testing with a coldwater speci es (Rainbow Trout) using degrad ate CL322,250 was listed as a data gap in the 2007 risk assessment. This data gap was fulfilled by MRID 46596010 and additionally a Bluegill Sunfis h acute test was submitted (MRID 46596009). All acute freshwater fish data requirements for the major degradates have been fulfilled. The results of the study confirm that degradate CL322,250 is believed to be less toxic than pa rent, tralopyril.

Freshwater Fish, Chronic

A freshwater fish early life-stage test using the technical grade of the active ingredient (TGAI) is anticipated to be required for tr alopyril because the end-use product is expected to be transported to water from the intended use site, and (1) tral opyril is intended for a use such that both the parent and it’s degradates will have a presence in water that is likely to be continuous or recurrent, and (2) aquatic acute LC 50 

### values are less than 1 mg/l for the parent and major degradate CL 322,250. The preferred test species is rainbow trout in this case because it is the most acutely sensitive species te sted, but other species may be us ed. However, if other species are used an acute test for the chronic tested spec ies is also needed to allow calculation of an acute-to-chronic ratio (ACR) . The ACR is then used to estimate the chronic value for the most acutely sensitive species. The results of chronic testing are summarized in Table 21; while there are fish early life stage test s with zebra fish there ar e no corresponding acute 96-hr LC 50 

### values which would allow calculation of ACR. Therefor e, chronic data for the most acutely sensitive species is anticipated to be re quired but may be addressed by either an acceptable zebra fish acute study or a rainbow trout ELS study.

Table 21. Toxicity Profile of Tralopyril Paren t and Degradates to Freshwater Fish, Acute and Chronic

Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

Econea technical 45893901 Zebrafish ( Danio rerio ) 33 days (ELS) NOAEC =0.17 ppb LOEC = 0.37 ppb Acceptable

Econea technical 46596002 Rainbow trout ( Oncorhynchus mykiss ) 96 hr LC 50 = 1.300 ppb NOAEC = 0.68 ppb Acceptable

Econea technical 46596003 Bluegill sunfish ( Lepomis macrochirus ) 96 hr LC 50 = 3.2 ppb NOAEC = 1.3 ppb Acceptable

CL 322,250 46596009 Bluegill sunfish ( Lepomis macrochirus ) 96 hr LC 50 = 1200 ppb NOAEC = 550 ppb Acceptable

CL 322,250 46596010 Rainbow trout ( Oncorhynchus mykiss ) 96 hr LC 50 = 520 ppb NOAEC = 320 ppb Acceptable

CL 322,250 46751307 Zebrafish ( Danio rerio ) 35 d (ELS) LOEC = 140 ppb NOAEC = 69 ppb Acceptable
ELS: early life stage test

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Page 60 of 66 Freshwater Invertebrates, Acute—Parent and Degradates

A freshwater aquatic invertebrate toxicity test us ing the technical grade of the active ingredient is anticipated to be required to establish the toxic ity of tralopyril to invert ebrates. The preferred test species is Daphnia magna . Results of this test using the pa rent, tralopyril, are listed in Table 22. The daphnid acute study (MRID #465960-01), was classified as supplemental due to unexplained low percent recoveries in the measured chemical analysis. Th e guideline deviations were corrected by the registrants (MRID 469179-01) and the study was reclassified as acceptable. The results indicate that parent tralopryil is very highl y toxic to aquatic invertebrates on an acute basis.

A freshwater aquatic invertebrate toxici ty test using major degradates CL322,250 and CL322,248, as well as minor degradate CL325,195 were also performed. Results of these tests are listed in Table 22. The results indicate that CL322,250 is moderately to highly toxic to aquatic invertebrates on an acute basis and that CL322,248 is slightly toxic to aquatic invertebrates on an acute basis. Results indi cate that minor degradate CL325,195 is moderately toxic to aquatic invertebrates on an acute basis.

Freshwater Invertebrates, Chronic

A freshwater aquatic invertebrate life-cycle test using the technical grade of the active ingredient (TGAI) was required for tralopyril be cause the end-use product is e xpected to be transported to water from the intended use site, and (1) tralopyril is intended for a use such that both the parent and it’s degradates will have a presence in water that is likely to be c ontinuous or recurrent, and (2) aquatic acute EC 50 

### values are less than 1 mg/l for th e parent and major degradate CL 322,250. Preferred test species is Daphnia magna . Freshwater aquatic in vertebrate life-cycle testing was required for tralopyril due to the likelihood of repeated or continuous exposure from boat hulls, as well as the high acute toxicity to fresh water invertebrates. Results of this test are listed in Table 22.

These studies show that the parent compound and degradates can cause growth and reproductive effects in aquatic invertebrates, but the degradat es are substantially less toxic than the parent compound.

Table 22 – Toxicity Profile of Tralopyr il Parent and Degradates to Freshwater Invertebrates, Acute and Chronic

Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

Econea technical 46596001 Water flea ( Daphnia
magna ) 48 hr EC 50 = 1.5 ppb NOAEC = 0.32 ppb Acceptable

Econea technical 46596004 Water flea ( Daphnia
magna ) 21 days (LC) NOAEC = 0.20 ppb a LOAEC = 0.57 ppb Acceptable

CL 325,195 45706902 Water flea ( Daphnia
magna ) 48 hr EC 50 = 3,510 ppb NOAEC = 2,700 ppb Supplemental

CL 322,250 46596008 Water flea ( Daphnia
magna ) 48 hr EC 50 = 510 ppb NOAEC = 250 ppb Acceptable

CL 322,250 45706903 Water flea ( Daphnia
magna ) 48 hr EC 50 = 1,630 ppb NOAEC = 1,000 ppb Supplemental

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Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

CL 322, 250 45674102 Water flea ( Daphnia
magna ) 48 hr EC 50 = 700 ppb NOAEC = 430 ppb Supplemental

CL 322,250 46596011 Water flea ( Daphnia
magna ) 21 days (LC) NOAEC = 300 ppb a LOAEC = 540 ppb Acceptable

CL 322,248 45674112 Water flea ( Daphnia
magna ) 48 hr EC 50 > 16,800 ppb NOAEC = 11,800 ppb Supplemental

CL 322,248 45674113 Water flea ( Daphnia
magna ) 21 days (LC) NOAEC > 1,370 ppb b Supplemental

LC: life cycle test

a ACR for econea and CL 322,250 (using only acceptable data) in D. magna is 7.5 and 1.7, respectively. ACR = acute value  chronic NOAEC. The acute NOAEC for CL 322,250 of 250 ppb is lower than the chronic NOAEC of 300 ppb, so the ACR based on this pairing is not sound and is an underestimate of the ACR.

b An ACR for CL 322,248 cannot be calculated because th e acute value and chronic NOAEC are both non-definitive values. 

## Toxicity to Estuarine and Marine Animals

Estuarine and Marine Fish, Acute—Parent and Degradates

Acute toxicity testing with estuarine/marine fish using the technical grade of the active ingredient (TGAI) is anticipated to be require d for tralopyril because it is intended for direct application to the marine/estuarine environmen t. The preferred test species is sheepshead minnow. This testing is anticipat ed to be required for antifoulants. Summaries of the results of studies submitted with tralopyril and degradates ar e provided in Table 23. The results indicate that tralopryil parent is highly toxic to estuarine/marine fi sh on an acute basis. All acute estuarine/marine fish data requirements have been fulfilled for the parent. The results indicate that CL322,250 is highly toxic to marine/estuarine fish on an acute basis, that CL322,248 is slightly toxic to estuarine/marine fish on an acute basis and that CL325,195 is slightly toxic to marine/estuarine fish on an acute basis.

Estuarine and Marine Fish, Chronic—Parent and Degradates

Fish early life-stage toxicity testing was c onducted using parent tral opyril, major degradate CL322,250, and minor degradate CL325,195. These data in Table 23 demonstrate that the parent compound and degradates are capable of impacti ng fish larval survival and growth. The degradates are substantially less toxic than the parent compound.

Table 23. Toxicity Profile of Tralopyril Paren t and Degradates to Estuarine and Marine Fish, Acute and Chronic

Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

Econea technical 45674003 Sheepshead minnow ( Cyprinodon variegatus ) 96 hr LC 50 = 23.71 ppb NOAEC = 10.0 ppb Acceptable

Econea technical 45674007 Sheepshead minnow ( Cyprinodon variegatus ) 34 d (ELS) NOAEC = 4.3 ppb a LOAEC = 8.7 ppb Acceptable

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Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

CL 325,195 45674013 Sheepshead minnow ( Cyprinodon variegatus ) 96 hr LC 50 > 16,000 ppb NOAEC > 16,000 ppb Supplemental

CL 325,195 45674017 Sheepshead minnow ( Cyprinodon variegatus ) 34 d (ELS) NOAEC = 1,300 ppb a LOAEC = 2,700 ppb Acceptable

CL 322,248 46751309 Sheepshead minnow ( Cyprinodon variegatus ) 96 hr LC 50 > 89,000 ppb NOAEC > 89,000 ppb Acceptable

CL 322,250 45674101 Sheepshead minnow ( Cyprinodon variegatus ) 96 hr LC 50 > 950 ppb NOAEC > 950 ppb Supplemental

CL 322,250 45674106 Sheepshead minnow ( Cyprinodon variegatus ) 34 d (ELS) NOAEC = 240 ppb a LOAEC = 510 ppb Acceptable

ELS: early life stage test

a ACR for tralopyril, CL325,195, and CL 322,250 in sheepshead minnow is 5.51, >12.3, and >3.96, respectively. ACR = acute value  chronic NOAEC.


### Estuarine and Marine Invertebrates, Acute—Parent and Degradates

Acute toxicity testing with estu arine/marine invertebra tes using the technical grade of the active ingredient (TGAI) was required fo r tralopyril because the end-use product is intended for direct application to the marine/estuarine environment a nd testing is required for its major degradate. The preferred test species are mysid shrimp and easte rn oyster. Results of these tests are listed in Table 24. The results indicate that parent tralopryil is very hi ghly toxic to estuarine/marine invertebrates on an acute basis. Estuarine/marine invertebrate acute toxi city studies using the degradates were also submitted. The resu lts indicate that CL322,250 is highly toxic to estuarine/marine invertebrates on an acut e basis, CL322,248 is moderately toxic to estuarine/marine invertebrates on an acute basis, and CL325,195 is slightly toxic to marine/estuarine invertebra tes on an acute basis.

Estuarine and Marine Invertebrates, Chronic—Parent and Degradates

An estuarine/marine invertebrate life-cycle toxicity test was required for tralopyril because the end-use product is expected to be transporte d to water from the in tended use site, and (1) tralopyril is intended for a use such that both the parent and it’s degradates will have a presence in water that is likely to be continuo us or recurrent, and (2) aquatic acute EC 50 

### values are less than 1 mg/l for the parent and major degradate CL 322,250. Results of these tests are listed in Table 24.

Table 24. Toxicity Profile of Tralopyril Paren t and Degradates to Estuarine and Marine Invertebrates, Acute and Chronic

Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

Econea technical 45674005 Eastern oyster ( Crassostrea virginica ) 96 hr (shell deposition) EC 50 = 0.56 ppb NOAEC = 0.19 ppb Supplemental

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Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

Econea technical 46751305 Eastern oyster ( Crassostrea virginica ) 96 hr (shell deposition) EC 50 = 0.64 ppb NOAEC = 0.29 ppb Acceptable

Econea technical 45674006 Mysid ( Americamysis bahia ) 96 hr LC 50 = 0.98 ppb NOAEC = 0.36 ppb Acceptable

Econea technical 45674009 Mysid ( Americamysis bahia ) 28 d (LC) NOAEC = 0.25 ppb a LOAEC = 0.51 ppb Supplemental

Econea technical 44911101 Mysid ( Americamysis bahia ) 28 d (LC) NOAEC = 2.28 ppb LOAEC = 4.2 ppb Acceptable (Study has a higher NOAEC than acute test)

CL 325,195 45674014 Eastern oyster ( Crassostrea virginica ) 96 hr (shell deposition) EC 50 = 14,000 ppb NOAEC = 6,900 ppb Acceptable

CL 325,195 45674015 Mysid ( Americamysis bahia ) 96 hr LC 50 = 12,250 ppb NOAEC = 5,300 ppb Acceptable

CL 322, 250 45674103 Eastern oyster ( Crassostrea virginica ) 96 hr EC 50 = 310 ppb NOAEC = 46 ppb Acceptable

CL 322, 250 45674104 Mysid ( Americamysis bahia ) 96 hr LC 50 = 550 ppb NOAEC = 330 ppb Acceptable

CL 322,250 46596012 Mysid ( Americamysis bahia ) 28 d (LC) NOAEC = 82 ppb LOAEC = 160 ppb Acceptable

CL 322,248 46751308 Mysid ( Americamysis bahia ) 96 hr LC 50 = 4300 ppb NOAEC = 2500 ppb Acceptable

LC: life cycle test

a ACR for tralopyril and CL 322,250 in Americamysis bahia is 3.92 and 6.7, respectively. ACR = acute value  chronic NOAEC.



### Benthic Invertebrates, Freshwater and Estuarine/Marine—Parent and Degradates

Sediment toxicity testing is anticipated to be required for tralopyril and its major degradate CL 322,250 because based on environmental fate charact eristics which indicate these chemicals are expected to partition to sediment , and ecological effects informati on which indicate high toxicity to aquatic invertebrate species. Parent tralopyril and its degradates are expected to be present in both the water and sediment compartments in wa ter bodies. Parent tralopyril will continually leach and any organisms present will be exposed to the parent compound and its degradates. Subchronic sediment testing was submitted for tralopryil and its major metabolites, and is summarized in Table 25. However, these are not chronic reproduction te sts. Tralopyril under acidic to neutral conditions is expe cted to predominate and be stable for greater than 10 days in freshwater environments and the major degrad ate CL 322,250 is expected to be stable in seawater conditions. Ther efore chronic reproduction tests are an ticipated to be required for the parent in freshwater and for the ma jor degradate CL 322,250 in seawater.

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Page 64 of 66 Table 25. Toxicity Profile of Tralopyril Parent and Degradates to Benthic Invertebrates, Freshwater and Estuarine/Marine

Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

Econea technical 45674010 Amphipod ( Hyalella
azteca ) 10D (subchronic) LC 50 = 2.2 mg/kg-sed NOAEC = 1.0 mg/kg-sed Acceptable

Econea technical 45674011 Amphipod ( Leptocheirus plumulosus ) 10 D (sub chronic) LC 50 = 1.1 mg/kg-sedNOAEC = 0.50 mg/kgsed Acceptable

CL 325,195 45674019 Amphipod ( Hyalella
azteca ) 10 D (subchronic) LC 50 = 49 mg/kg-sed NOAEC = 49 mg/kg-sed Supplemental

CL 325,195 45674020 Amphipod ( Leptocheirus plumulosus ) 10 D (subchronic) LC 50 = 27 mg/kg-sed NOAEC = 27 mg/kg-sed Acceptable

CL 322,248 45674114 Amphipod ( Leptocheirus plumulosus ) 10 D (subchronic) LC 50 = 75 mg/kg-sed NOAEC = 75 mg/kg-sed Acceptable

CL 322,248 45695804 Amphipod ( Hyalella
azteca ) 10 D (subchronic) LC 50 = 37 mg/kg-sed 37 mg/kg-sed Acceptable

CL 322, 250 45674108 Amphipod ( Hyalella
azteca ) 10 D (subchronic) LC 50 = 35 mg/kg-sed NOAEC = 35 mg/kg-sed Acceptable

CL 322, 250 45674109 Amphipod ( Leptocheirus plumulosus ) 10 D (subchronic) LC 50 = 70 mg/kg-sed NOAEC = 70 mg/kg-sed Acceptable



## Toxicity to Plants

Terrestrial/Semi-Aquatic Plants—Parent and Minor Degradate

Currently, semi-aquatic plant testing is anticipate d to be required for antifoulant pesticides on one species, rice ( Oryza sativa ). Studies were conducted us ing parent tralopyril and minor degradate CL325,195. Results of the st udies are listed in Table 26.

Table 26. Toxicity Profile of Tralopyril Parent and Degradates to Terristrial/Semi Aquatic Plants

Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

Econea technical 45674115 Rice ( Oryza sativa ) 14 D EC 25 > 0.17 ppm NOAEC ≥ 0.17 ppm Acceptable

CL 325,195 45674115 Rice ( Oryza sativa ) 14 D EC 25 > 0.17 ppm NOAEC > 0.17 ppm Acceptable

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Page 65 of 66 Aquatic Plants—Parent and Degradates

Aquatic plant testing is required for antifoulant pesticides such as tralopyril. Testing is required on one vascular plant ( Lemna sp.), and four species of algae. Results of submitted studies for tralopryil and major degradates are summarized in Table 27.

Table 27. Toxicity Profile of Tralopyril Parent and Degradates to Aquatic Plants

Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

Econea technical 45674117 Freshwater green algae ( Raphidocelis subcapitata ) 96 Hr IC 50 = 4.49 ppb NOAEC = 3.1 ppb Supplemental

Econea technical 45674118 Marine diatom ( Skeletonema

costatum ) 96 Hr IC 50 = 2.88 ppb NOAEC = 0.54 ppb Supplemental

Econea technical 45893902 Bluegreen algae ( Anabaena flos-aquae ) 96 hr IC 50 = 350 ppb NOAEC = 9.2 ppb Acceptable

Econea technical 45893903 Freshwater diatom ( Navicula pelliculosa ) 96 hr IC 50 = 5.5 ppb NOAEC = 0.99 ppb Acceptable

Econea technical 46596006 Freshwater green algae ( Pseudokirchneriella subcapitata ) 96 hr IC 50 = 11 ppb NOAEC = 6.8 ppb Acceptable

Econea technical 46619901 Marine diatom ( Skeletonema

costatum ) 96 hr IC 50 = 2.7 ppb NOAEC = 1.5 ppb Acceptable

CL 325,195 45674116 Duckweed ( Lemna gibba ) 7 D IC 50 = 87.2 ppb NOAEC = 22 ppb Acceptable

CL 325,195 45674119 Duckweed ( Lemna gibba ) 7 D IC 50 = 13,000 ppb NOAEC = 5,900 ppb Acceptable

CL 325,195 45674120 Green algae ( Raphidocelis subcapitata ) 96 Hr IC 50 = 440 ppb NOAEC = 230 ppb Supplemental

CL 325,195 45674121 Marine diatom ( Skeletonema

costatum ) 96 Hr IC 50 = 470 ppb NOAEC = 280 ppb Supplemental

CL 325,195 45893906 Freshwater diatom ( Navicula pelliculosa ) 96 hr IC 50 = 1,510 ppb NOAEC = 850 ppb Acceptable

CL 325,195 45945201 Bluegreen algae ( Anabaena flos-aquae ) 96 hr IC 50 = 6,500 ppb NOAEC = 1,400 ppb Acceptable

CL 322,250 45674122 Duckweed ( Lemna gibba ) 7 D IC 50 = 990 ppb NOAEC = 530 ppb Supplemental

CL 322,250 45674123 Green algae ( Raphidocelis subcapitata ) 96 Hr IC 50 = 4,620 ppb NOAEC = 1,150 ppb Supplemental

CL 322,250 45674124 Marine diatom ( Skeletonema

costatum ) 96 Hr IC 50 = 1,140 ppb NOAEC = 180 ppb Supplemental

CL 322,250 45893907 Bluegreen algae ( Anabaena flos-aquae ) 96 hr IC 50 > 830 ppb NOAEC > 830 ppb Supplemental

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Chemical MRID Test Species Study Duration Toxicity Endpoint Classification

CL 322,250 45893908 Freshwater diatom ( Navicula pelliculosa ) 96 hr IC 50 > 930 ppb NOAEC > 930 ppb Supplemental

CL 322,250 46596014 Marine diatom ( Skeletonema

costatum ) 96 hr IC 50 = 660 ppb NOAEC = 500 ppb Acceptable

CL 322,248 45674125 Duckweed ( Lemna gibba ) 7 d IC 50 > 930 ppb NOAEC > 930 ppb Supplemental

CL 322,248 45674126 Green algae ( Raphidocelis subcapitata ) 96 hr IC 50 > 1.99 ppm NOAEC > 1.99 ppm Supplemental

CL 322,248 45674127 Marine diatom ( Skeletonema

costatum ) 96 hr IC 50 = 1,200 ppb NOAEC = 160 ppb Supplemental

CL 322,248 45893904 Bluegreen algae ( Anabaena flos-aquae ) 96 hr IC 50 > 1000 ppb NOAEC = 1000 ppb Supplemental

CL 322,248 45893905 Freshwater diatom ( Navicula pelliculosa ) 96 hr IC 50 > 980 ppb NOAEC > 980 ppb Supplemental



### .