Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 2 of 69

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

Rose Kyprianou

Marshall Swindell

Office of General Counsel

Philip Ross
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 3 of 69

Table of Contents

1 Introduction............................................................................................................................. 5

1.1 Statutory and Regulatory Authority ................................................................................. 5

1.2 Updates to the Work Plan................................................................................................. 7

1.3 Case Overview ................................................................................................................. 7

1.4 Chemical Identification and Properties............................................................................ 8

1.5 Use/Usage Description................................................................................................... 10

1.5.1 Registrations ........................................................................................................... 10

1.5.2 Usage Information .................................................................................................. 11

1.6 Regulatory History ......................................................................................................... 11

1.6.1 Recent/Pending Regulatory Actions....................................................................... 12

1.6.2 Tolerance Information ............................................................................................ 12

1.7 Incidents......................................................................................................................... 12

1.7.1 Human Health ......................................................................................................... 12

1.7.2 Ecological ............................................................................................................... 12

2 Anticipated Data Needs ........................................................................................................ 12

3 Human Health Risk Assessment........................................................................................... 15

3.1 Existing Toxicological Endpoints.................................................................................. 15

3.2 Dietary Exposure............................................................................................................ 17

3.2.1 Food ............................................................................................................................ 17

3.2.2 Drinking Water ........................................................................................................... 17

3.3 Occupational and Residential Exposures....................................................................... 18

3.3.1 Occupational Handler Exposure ............................................................................. 18

3.3.2 Residential Handler Exposures............................................................................... 20

3.3.3 Residential Post-Application Exposures...................................................................... 20

3.4 Aggregate and Cumulative Exposure............................................................................. 21

3.4.1 Aggregate Exposures.............................................................................................. 21

3.4.2 Cumulative Exposures............................................................................................ 21

4 Environmental Risk Assessment........................................................................................... 21

4.1 Environmental Fate and Exposure Pathways................................................................. 22

4.2 Ecological Effects Assessment....................................................................................... 25

4.2.1 Mode of Action....................................................................................................... 25

4.2.2 Measures of Effect (Ecotoxicology Assessment Endpoints).................................. 25

4.3 Exposure Analysis Plan.................................................................................................. 30

4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates.................................................. 30

5 Endocrine Disruptor Screening Program (EDSP)................................................................. 31

6 Optional Label Changes........................................................................................................ 32

7 Next Steps............................................................................................................................. 32

8 References............................................................................................................................. 32

Appendix A Toxicology Profile............................................................................................... 40

Appendix B Environmental Fate ............................................................................................. 47

Appendix C Ecotoxicology Profile.......................................................................................... 55

Appendix D Comments Received Concerning the Preliminary Work Plan............................ 65
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 4 of 69

List of Tables

Table 1 – Summary of Anticipated Risk Assessments and Data Needs: Tralopyril ...................... 6

Table 2 – Anticipated Registration Review Schedule .................................................................... 7

Table 3 – Chemical Identification of Tralopyril ............................................................................. 8

Table 4 – Physical-Chemical Properties for Tralopyril ................................................................. 9

Table 5 – Chemical and Physical Properties of Tralopyril Degradates........................................ 10

Table 6 – Distribution of Products by Specific Alkylbenzene Sulfonate ..................................... 11

Table 7 – Summary of Tralopyril Registered Uses ...................................................................... 11

Table 8 – Studies Anticipated as Needed for the Registration Review of Tralopyril................... 13

Table 9 – Existing Toxicological Endpoints for Dietary Exposure to Tralopyril......................... 16

Table 10 – Existing Toxicological Endpoints for Occupational/Residential Exposure to 

Tralopyril ...................................................................................................................................... 16

Table 11 – Occupational Handler Exposure Scenarios for Tralopyril.......................................... 19

Table 12 – Residential Handler Exposure Scenarios for tralopyril .............................................. 20

Table 13 – Selected Effects Endpoints for the Ecological Risk Assessment of Tralopyril.......... 26

Table 14 – Selected Effects Endpoints for the Ecological Risk Assessment of Tralopyril's Major 

Degradate CL322,250 ................................................................................................................... 27

Table 15 – Selected Effects Endpoints for the Ecological Risk Assessment of Tralopyril's Major 

Degradate CL322,248................................................................................................................... 29

Table 16 – Acute Toxicity Data for Tralopyril............................................................................. 40

Table 17 – Summary of parent tralopyril half-lives and degradate amounts and half-lives in 

environmental fate studies ............................................................................................................ 49

Table 18 – Sorption (Kf/Koc) of parent tralopyril and its main degradates................................. 50

Table 19 – Physical-Chemical Properties for Tralopyril and its Primary Metabolites................. 50

Table 20 – Reviewed and Accepted Paint Leaching Studies for Tralopyril in Seawater............. 51

Table 21 – Toxicity Profile of Tralopyril Parent and Degradates to Birds................................... 56

Table 22 – Toxicity Profile of Tralopyril Parent and Degradates to Freshwater Fish, Acute and 

Chronic.......................................................................................................................................... 57

Table 23 – Toxicity Profile of Tralopyril Parent and Degradates to Freshwater Invertebrates, 

Acute and Chronic ........................................................................................................................ 58

Table 24 – Toxicity Profile of Tralopyril Parent and Degradates to Estuarine and Marine Fish, 

Acute and Chronic ........................................................................................................................ 59

Table 25 – Toxicity Profile of Tralopyril Parent and Degradates to Estuarine and Marine 

Invertebrates, Acute and Chronic ................................................................................................. 60

Table 26 – Toxicity Profile of Tralopyril Parent and Degradates to Benthic Invertebrates, 

Freshwater and Estuarine/Marine ................................................................................................. 62

Table 27 – Toxicity Profile of Tralopyril Parent and Degradates to Terristrial/Semi Aquatic 

Plants............................................................................................................................................. 62

Table 28 – Toxicity Profile of Tralopyril Parent and Degradates to Aquatic Plants.................... 63

List of Figures

Figure 1 – Conceptual Model for Ecological Exposure and Effects of Tralopyril to Aquatic 

Organisms from the Antifoulant Use............................................................................................ 25
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 5 of 69

1 Introduction 

This document is the Environmental 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 explained what EPA's Office of Pesticide Programs knows about tralopyril, 

highlighting anticipated data and assessment needs, 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. This work plan addresses public comments received 

concerning the PWP, which was posted in the tralopyril registration review docket (EPA-HQOPP-2013-0217) on June 26, 2013. A public comment period was initiated, which concluded on 

August 26, 2013. Further, this document makes final the work plan for the tralopyril registration 

review process.

1.1 Statutory and Regulatory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States 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 risks to human health or the environment when 

used as directed on product labeling. The registration 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 the statutory standard of no unreasonable 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 marketplace can be used safely. 

Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/.

The Agency is implementing the registration review 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 the FIFRA standard for 

registration. The regulations governing registration 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 registration review decision. 

Documents associated with this registration review can be viewed at http://www.regulations.gov 

in docket EPA-HQ-OPP-2013-0217. Below is a summary of the issues relevant to this 

registration review case. 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 6 of 69

Table 1 – Summary of Anticipated Risk Assessments 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 8 for more detail about 

anticipated data needs)

Dietary (food) No N/A None None 

Dietary (drinking water) Yes 4/16/2008 Updated 

Developmental Toxicity (non-rodent)

Reproductive Toxicity

Chronic Oral Toxicity

Cancer Study

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

Inhalation Exposure , Outdoor

Residential Handler Yes 4/10/2008 Updated Dermal Exposure, Outdoor

Inhalation Exposure, Outdoor

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 (special 

study) for parent tralopyril (anticipated 

study will need to address CL 322,250)

Avian reproduction study with tralopyril

Acute zebra fish study or a rainbow 

trout fish early life stage study with 

tralopyril (data from the parent expected 

to be used as surrogate for major 

degradates)

Freshwater benthic invertebrate chronic 

reproduction study one with an 

amphipod and one with a chironomid for 

the parent (special studya)

Saltwater benthic invertebrate with an 

amphipod for CL 322,250 (special 

studya)

pKa values for CL 322,250 and CL 

322,248

Log Kow values for CL 322,250, CL 

322,248, and CL 325,195

N/A = Not applicable

a The anticipated Data Call-In Notice (DCI) will provide that protocols need to be required to be submitted for review prior to conduct of the 

study. Because of the photodegradation potential, The anticipated DCI will require that sediment in test vessels should be shielded to reduce bias 

from laboratory lighting and design.
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 7 of 69

Table 2 – Anticipated Registration Review Schedule

Anticipated Activity Target Date*Completion Date

Phase 1: Opening the Docket 

Open Docket and 60-Day Comment Period for Preliminary Work Plan 2013-06 2013-06-26

Close Public Comment Period 2013-08 2013-08-26

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

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 Updates to the Work Plan

Since the publication of the PWP, the agency has made the following updates:

Added this section “Updates to the Work Plan.”

Updated the dates in Table 2.

Removed study entitled “In vitro Salmonella typhimurium Reverse Mutation Assay” 

from Table 8.

Updated Table 13 to include an additional acute toxicity study in the rat per response to 

public comments.

Removed the Guidance for Commenters Section.

Added Appendix D “Comments Received Concerning the Preliminary Work Plan.”

Added other minor edits to the Final Work Plan.

The Agency received fourteen comments on the initial docket. The comments received changed 

the data requirements (see above) and timeline described in the PWP. A summary of the 

comments received and the Agency’s responses are presented in Appendix D.

1.3 Case Overview

The docket for tralopyril (Case 5114) has been established at http://www.regulations.gov in 

docket number EPA-HQ-OPP-2013-0217. 

Tralopyril is registered for use as antifoulant in paint for both recreational and commercial 

vessels in fresh and salt water. There are two technical products that contain 93.2 and 99 percent 

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 products also contain zinc pyrithione (ZPT). 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 8 of 69

The products can be applied by brush, roller and airless sprayer. Two or three coats are 

recommended for best performance. 

Some of the tralopyril end use products that contain ZPT prohibit airless sprayer application by 

residential (non-commercial) users and require that residential users apply no more than one coat 

within a 24 hour time period. These restrictions are based on the ZPT RED (not based on 

tralopyril). All products are antifouling paints registered for use on ships hulls and bottoms and 

are applied using an airless spray gun system.

1.4 Chemical Identification and Properties

Table 3 presents the two active ingredients to be assessed in Case 4006: Sodium dodecylbenzene 

sulfonate (PC Code: 079010) and Dodecylbenzene sulfonic acid (PC Code: 098002). The major 

difference between these actives are the ions on the sulfonate groups which are sodium versus 

hydrogen respectively, both ionize. ABS product chemistry information relevant to risk 

assessment is summarized in Table 3.

Table 3 – Chemical Identification 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-bromo-5-trifluoromethyl pyrrole;

Tralopyril

Classification Halogenated Pyrrole Nitrile

PC Code 119093

CAS No. 122454-29-9

Molecular Formula C12H5BrClF3N2

Molecular Weight 349.53 g/mol

Available Bromine 45.72%

Available Chlorine 20.28%

Available Fluorine 32.62%

Molecular Structure:
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 9 of 69

The parent tralopyril product chemistry information (source: MRIDs 45673902, 45673903, 

45673906, 45673907 and 48596802) relevant to risk assessment is summarized in Table 4 and 

details of the environmental fate properties are discussed in Appendix B. 

Table 5 below contains the chemical and physical properties of the tralopyril degradates CL 

322,250, CL 322,248, and CL 325,195.

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/cm3at 20oC

830.7370 Dissociation Constant in water pKa = 7.08 at 26 C

830.7550 Partition coefficient (noctanol/water) Log Kow3.5

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
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 10 of 69

Guideline 

Number Physical and Chemical Properties Value

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

Table 5 – Chemical and Physical Properties 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 C11 H6 Br1 CL1 N2 C12H6F3ClN2O2 C11H7CLN2

Molecular Weight g/ml 281.54 302.64 248.67

Molecular Structures:

Log P (Log Kow) 3.7224.1721.682

Solubility in water mg/l 5.63 17.95 476

Vapor pressure mm Hg at 

25 C

7.62 x 10-73.45 x 10-97.0 x 10-11

Henry’s Law (m

3mol-1

) 5 x 10-87.65 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.

1.5 Use/Usage Description

1.5.1 Registrations

There are 11 registered products that contain tralopyril. The products are presented in Table 6. 

Most of the products are powder and solid at room temperature.

C

N

Cl

N OH

HO
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 11 of 69

Table 6 – Distribution of Products by Specific Alkylbenzene Sulfonate

Chemical 

Name

PC 

Code % ai Formulations Registered Products

Tralopyril 119093 2.9 -

99%

Soluble Concentrate; 

Ready to Use

577-570, 2693-220, 2693-230, 7313-EA, 9339-GG, 

43813-27, 43813-52,44891-19, 60061-134, 60061-

137, 74681-28 

A listing of the registered uses of tralopyril is included in Table 7. Tralopyril is registered for 

use as antifoulant in paint for both recreational and commercial vessels in fresh and salt water. 

There are two technical products that contain 93.2 and 99 percent tralopyril and nine end use 

products that contain 2.9 to 7.28 percent tralopyril. One of the end use products contains only 

tralopyril and the other end use products also contain zinc pyrithione (ZPT). The products can 

be applied by brush, roller and airless sprayer. Two or three coats are recommended for best 

performance. 

Some of the tralopyril end use products that contain ZPT prohibit airless sprayer application by 

residential (non-commercial) users and require that residential users apply no more than one coat 

within a 24 hour time period. These restrictions are based on the ZPT RED (not based on 

tralopyril). All products are antifouling paints registered for use on ships hulls and bottoms and 

are applied using an airless spray gun system.

Table 7 – 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 ft2/gallon

1.5.2 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. 

1.6 Regulatory History 

The first product containing tralopyril (Econea®), 4-bromo-2-(4-chlorophenyl)-5-

(trifluoromethyl)-1H-pyrrole-3-carbonitrile, was received in May of 2002 as a technical product 

with approved uses to formulate a non-copper based antifoulant coating. The first end use and 

technical products containing tralopyril were registered in 2007. There are currently 2 technical 

and 9 end use products with tralopyril as an active ingredient. There are currently no outstanding 

Data Call-In data requirements for this active ingredient. There are no products containing this 

ingredient as an inert ingredient.
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 12 of 69

1.6.1 Recent/Pending Regulatory Actions 

There are currently no products containing tralopyril awaiting a registration decision.

1.6.2 Tolerance Information

There are no tolerances or exemptions from tolerances for tralopyril because there are no 

currently registered uses for this active ingredient associated with food or feed. 

1.7 Incidents

1.7.1 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 state health and environmental agencies and individual consumers, 

submitted to OPP since 1992. As of June 4, 2013, no incidents have been reported in IDS 

associated with tralopyril use from 1992 to the present.

1.7.2 Ecological

No tralopyril ecological incidents have been reported in the Agency’s Ecological Incident 

Information System (EISS) for the time period spanning 2005 to 2012.

2 Anticipated Data Needs 

Table 8 presents a summary of the data anticipated as being needed to support this registration 

review.
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 13 of 69

Table 8 – Studies Anticipated as Needed for the Registration Review of Tralopyril

GLN Study Name Test 

Substance

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk Assessment(s) 

Data Will Support

Use Site(s) 

Triggering 

Anticipated Data 

Requirement

Applicable Exposure Scenarios

Studies Anticipated to be Required through the Registration Review DCI

875.1200

887.1400

Outdoor Exposure, Dermal

Outdoor Exposure, Inhalation tralopyril 36 Occupational HandlerResidential Handler Antifoulant Paint 

Airless Spray Application by Commercial 

Painters 

Brush/Roller Application by Do it Yourself 

Painters 

870.3700 Developmental Toxicity 

(non-rodent species) tralopyril 24 Drinking Water Antifoulant Paint (Fresh Water Uses)

Oral exposures to drinking water 

contaminated with tralopyril or its 

degradates.

870.3800 or 

OECD 4435 Reproductive Toxicity

tralopyril

24

Drinking Water Antifoulant Paint 

(Fresh Water Uses)

Oral exposures to drinking water 

contaminated with tralopyril or its 

degradates.

870.4100 Chronic Oral Toxicity 

tralopyril

36

Drinking Water Antifoulant Paint 

(Fresh Water Uses)

Oral exposures to drinking water 

contaminated with tralopyril or its 

degradates.

870.4200 Cancer Study

tralopyril

36

Drinking Water Antifoulant Paint 

(Fresh Water Uses)

Oral exposures to drinking water 

contaminated with tralopyril or its 

degradates.

850.1075 or 

850.1400

Acute (zebra fish) or Earlylife Stage (rainbow trout) tralopyril 24 Ecological Antifoulant paint 

(Fresh water Uses)

Exposure of aquatic organisms to tralopyril 

or its degradates in surface water

Special 

Study1

Whole sediment; chronic 

invertebrates freshwater (2 

species—1 amphipod and 1 

chironomid)

tralopyril 24 Ecological 

Antifoulant paint 

(Fresh and salt 

water uses)

Exposure of aquatic organisms to tralopyril 

or its degradates in sediment

Special 

Study2

Whole sediment, chronic 

marine invertebrate 

(1 species-amphipod)

CL 322,250 24 Ecological Antifoulant paint 

(Salt water uses)

Exposure of saltwater benthic organisms to 

its degradates in sediment

850.2300 Avian Reproduction tralopryil 24 Ecological Antifoulant paint 

(Fresh water uses)

Exposure of aquatic organisms to tralopyril 

or its degradates in surface water
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 14 of 69

GLN Study Name Test 

Substance

Time Frame 

(Measured in 

months from 

DCI Receipt)

Risk Assessment(s) 

Data Will Support

Use Site(s) 

Triggering 

Anticipated Data 

Requirement

Applicable Exposure Scenarios

Special 

Study3

Leaching from antifoulant 

paint in freshwater

EP (monitor 

tralopyril 

and 

degradates) 12

Ecological Antifoulant Paint 

(Fresh Water Uses)

Oral exposures to drinking water 

contaminated with tralopyril or its 

degradates.

Exposure of aquatic organisms to tralopyril 

or its degradates in surface water. 

830.7550 or 

830.7560 or 

830.75704

Log Kow

CL 322,250

CL 322,248

CL 325,195

12 

Ecological Antifoulant Paint 

(Fresh and salt 

water use)

Exposure of aquatic organisms to tralopyril 

degradates in surface water

1 Based on log P (Log Kow) of >3, Koc values of 5,571-23,150 ml/g, and a half-life of >10 days.

2 The anticipated DCI requiring this special study will require the submission of a protocol for review prior to conduct of the study. 

3 The registrant has not submitted any data on leaching of tralopyril and its degradates in freshwater. All submitted leaching data employed artificial seawater and 

the Agency assumes that boats currently in ocean water can be transported and used in freshwater, creating exposure. Leaching data are anticipated to be needed 

for each registered paint.

4

The EPI-Suite 4.1 values are questionable because the experimental log P value for parent tralopyril with 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 a 

lower log P value than the parent compound.

5EPA considers the OECD Extended One-Generation Reproductive Toxicity Study (OECD 443) to be an acceptable substitute for GLN 870.3800 Two-Generation 

Reproduction. 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 15 of 69

3 Human Health Risk Assessment

EPA anticipates the need to revise the existing toxicological endpoints as part of this registration

review. Tables 9 and 10 presents the endpoints used in EPA’s most recent human health risk 

assessments.

3.1 Existing Toxicological Endpoints

Several toxicological studies were identified as data gaps and as anticipated data needs for 

registration review based on currently registered uses. All available information including 

existing toxicology studies, valid scientific literature, and the studies that are expected to be 

required for registration review will be considered in establishing the endpoints to be used in the 

registration review risk assessment. The following issues regarding these endpoints will also 

need to be addressed:

The inhalation exposures were assessed in the initial registration decision using an 

endpoint of 5.7 mg/kg/day that was converted from a 90 day inhalation toxicity study in 

rats where the LOAEL was 20 mg/m3based on portal of entry effects. This conversion 

was made so that the PHED unit exposure data, 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 reported in terms of air concentration, will be 

used and these exposures will be assessed using a human equivalent concentration 

(HEC). It is estimated that the HEC would equal 24 mg/m3using 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 factor 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/m3by the uncertainty factor of 

100 yields an “RfC” of 0.24 mg/m3as 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 initial registration decision using an endpoint of 

1000 mg/kg/day for systemic effects from a dermal toxicity study. This endpoint will not 

be used during registration review because dermal 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 represented by the NOAEL of 100 mg/kg/day for the appearance 

of sores that were observed at the LOAEL of 300 mg/kg/day. 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 16 of 69

Table 9 – Existing Toxicological Endpoints for Dietary Exposure to Tralopyril

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

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 10 – Existing Toxicological Endpoints for Occupational/Residential 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 for 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/m3) (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/m3based 

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 Risk assessment not required based for this use pattern
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 17 of 69

Long-Term 

(6 months – lifetime)

Cancer No cancer data available 

*Note - The toxicological endpoint 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. 

3.2 Dietary Exposure

3.2.1 Food 

There are no food uses for tralopyril. Therefore, EPA does not anticipate the need to conduct a 

dietary (food) risk assessment.

3.2.2 Drinking Water 

The U.S. EPA conducted a drinking water assessment in 2008 and results were summarized in a 

memorandum dated April 16, 20081. 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 paint uses were not considered of concern at 

that time. After reviewing the 2008 risk assessment, the Agency has concluded that it is 

necessary to update the previous drinking water assessment. This is due to advances in the 

scientific tools and models available to the Agency since conducting the 2008 assessment. A 

summary of planned revisions to the drinking water assessment are as follows: 

More recent version of DEEM-FCIDTM: The 2008 memo states that the risk 

assessment was conducted using the Dietary Exposure Evaluation Model (DEEMFCIDTM, Version 2.02) DEEM-FCIDTM which uses food and drinking water consumption 

data from the U.S. Department of Agriculture’s Continuing Surveys of Food Intakes by 

Individuals (CSFII) for 1994-1996 and 1998. A newer version (3.18) of DEEM-FCIDTM 

is currently available2,3that contains more recent food commodity consumption data 

derived from the National Health and Nutrition Examination Survey/”What We Eat in 

America” for 2003-20084. 

A newer version of MAM-PEC (3.0)5is currently available. The most recent version 

will be used to estimate refined drinking water residue values. 

Drinking water residue values will be further updated based on the development of 

a freshwater lake scenario in MAM-PEC. 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 

(MAM-PEC) for the primary degradation products of tralopyril, CL 322,250 and CL 

 

1 U.S. EPA (United States Environmental Protection Agency). 2008. An AD Memo from Talia Lindheimer to Marshall Swindell 

on “Acute and Chronic Drinking 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-2013-0217

www.regulations.gov

Page 18 of 69

322,248. MAM-PEC is an integrated hydrodynamic and chemical fate model that 

provides predictions of environmental concentrations of antifouling products in various 

aquatic environments. The model has traditionally 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 developing a fresh water 

lake scenario which will allow the Agency to update the drinking water residue values as 

appropriate. 

Availability of freshwater leaching data: due to the development of a fresh water lake 

scenario in MAM-PEC, the Agency expects to refine the MAM-PEC 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 anticipated 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 leaching 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 tralopyril used in the drinking water assessment are summarized in a 2008 

memorandum6. 

3.3 Occupational and Residential Exposures

Occupational and residential exposures are anticipated during the application of tralopyril 

containing antifoulant paints to commercial vessels 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 need to be updated. These assessments will need to be 

reassessed using the updated values. Outdoor Dermal (875.1200) and Inhalation (875.1400) 

Exposure studies are anticipated as being needed to supply the updated unit exposure values.

3.3.1 Occupational Handler Exposure

Occupational handler dermal and inhalation exposures to tralopyril were assessed for handlers 

spraying antifoulant paint products onto ships7. This assessment was based on a product (Sigma 

Nexxum 20) which contained 3.4 percent tralopyril and had coverage of 220 feet ft2/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 respirators, full face powered air 

purifying respirators (PAPR) and full face supplied air respirators. The dermal unit exposures 

 

6 U.S. EPA (United States Environmental Protection Agency). 2008. An AD Memo from James Breithaupt to 

Marshall Swindell entitled, “Environmental Fate Assessment 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-2013-0217

www.regulations.gov

Page 19 of 69

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 exceeded 100 only if the two highest levels of 

respiratory protection (Full face PAPR or full face SAR) were worn. 

The labels generally require dermal PPE (i.e. gloves) that yield dermal MOEs of 100 but they do 

not require respiratory protection that yields MOEs of 100. Some 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 cartridge 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 state that full face respirators with organic vapor 

cartridges and P-100 prefilters are required for spray applications.

The occupational handler exposures listed in Table 11 will need to be reassessed during 

registration review to account for the following factors that have changed:

The product assessed at the time of registration (11350-GL: Sigma Nexxium 20 

Antifouling) had 3.4 percent tralopyril7. Since that time other products have been 

registered that have as much as 7.28 percent tralopyril.

The assessment was done using PHED unit exposure 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/m3per lb ai handled when expressed 

as an 8 hour time weighted average (TWA) and some are above the PHED unit exposure 

of 48 ug/m3/lb ai expressed as an 8 hour TWA.

The amount of paint handled was assumed in the occupational exposure assessment7to be 

either 14 gallons based on an observational study submitted by the registrant (MRID 

468466-02) or 50 gallons based on a standard AD assumption that had been derived from 

an industry estimate provided by the American Chemistry Council in 2005. In 

comparison, the amount handled in the ZPT shipyard study ranged from 12 to 83 gallons 

with an average of 35 gallons.

Table 11 – Occupational Handler Exposure Scenarios for Tralopyril

Scenario Exposure Route(s) Duration

Airless Sprayer Application of Antifoulant Paint Inhalation Short, Intermediate, and Long Term 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 20 of 69

3.3.2 Residential Handler Exposures

Residential handler dermal and inhalation exposures to tralopyril were assessed for the 

application of tralopyril antifoulant paint products onto pleasure craft8. This assessment was 

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 assessed using data from a literature study9. The 

amount of paint handled was based on the hull sizes of 14, 20 and 30 feet, coverage of 400 ft2per 

gallon and one to three coats painted within a 24 hour period. The dermal MOEs ranged from 

360 to 4,300 without gloves and the inhalation 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 registration had 3.9 percent tralopyril. Since that 

time other products have been registered that 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 are 312 mg/lb ai with long sleeved shirt, long 

pants and no gloves and 41 mg/lb ai with long sleeved shirt, long pants and gloves. 

These values are greater than the corresponding 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 12 – Residential Handler Exposure Scenarios for tralopyril

Scenario Exposure Route(s) Duration

Applying Paint Using Brushes and Rollers Dermal Short Term 

3.3.3 Residential Post-Application Exposures

Because tralopyril is used only as an antifoulant paint, residential post application exposures are 

not anticipated.

 

8

Residential Exposure and Risk Assessment of the End Use 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-(trifluoremethyl), as an Antifoulant in Paint for Pleasure Craft and Do-it-Yourself Applications, 

D384689, 4/10/ 2008.

9

Potential Exposure of Amateurs (Consumers) through Painting 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-2013-0217

www.regulations.gov

Page 21 of 69

3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures

Prior to the registration of tralopyril, assessments were conducted for dietary exposures from 

drinking water and for dermal and inhalation exposures from residential handler application of 

paints to pleasure craft; however, an aggregate assessment was not conducted. Upon a 

reevaluation and selection of toxicological endpoints, combined with the updated human health 

exposure assessments expected as a part of this registration review case, aggregate exposures 

may need to be assessed. This assessment may include dietary (drinking water) exposures and 

residential exposures. 

3.4.2 Cumulative Exposures

With respect to cumulative exposure, unlike other pesticides for which EPA has followed a 

cumulative risk approach based on a common mechanism of toxicity, EPA has not made a 

common mechanism of toxicity finding as to tralopyril and any other substances, and tralopyril

does not appear to produce a toxic metabolite produced 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 mechanism 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 assessment and environmental risk characterization 

for tralopyril and its degradates in April of 200710 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 time of registration. The Agency will conduct a 

comprehensive updated ecological risk assessment for the antifoulant use of tralopyril. 

The Agency anticipates needing the following data in order to conduct 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; Chronic Invertebrates Freshwater and Marine

Leaching from antifoulant paint in fresh water (EP with monitoring of tralopyril and its 

major degradates)

 

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-2013-0217

www.regulations.gov

Page 22 of 69

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. 

The Agency has not conducted a risk assessment that supports a complete endangered species 

determination. The planned update to the ecological risk assessment conducted during 

registration review will allow the Agency to determine whether tralopyril’s use has 'no effect' or 

'may affect' federally listed threatened or endangered species (listed species) or their designated 

critical habitats. If the assessment indicates that tralopyril (parent and degradates/metabolies) 

“may affect” a listed species or its designated critical habitat, the assessment will be refined. A

more refined assessment involves clear delineation of the action area associated with proposed 

use of tralopyril antifoulant and use of best available information 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 and 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 different aquatic models 

were used to predict expected environmental concentrations (EEC’s) in harbors, marinas, bays, 

and channels in U.S. waters; the assessment included application to naval vessels, commercial 

ships, cruise ships, and pleasure craft. Model runs submitted were reviewed for completeness 

and accuracy by the Agency. Marine Antifouling 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 review indicates that additional information on 

environmental fate and ecological toxicity for parent tralopyril is needed to assess the risk to 

endangered and threatened federally listed (i.e., listed) species. Further review of the 

environmental fate studies indicates that the freshwater leaching rate used in the assessment was 

found not to be supported by any data in the Agency’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 the log Kow of the CL 322,250, CL 322,248, and CL 

325,195 degradates needs to be submitted. These log Kow values will be used in modeling. 

Also, the stability of the degradates in sediment raises concerns over reproductive effects for 

aquatic benthic invertebrates but only subchronic (10-day) study results are available. The 

Agency plans to conduct an endangered species risk assessment that addresses 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 (defluorinated parent compound). Aquatic exposure 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 23 of 69

will be primarily from the CL 322,250 degradate, which is more persistent than parent 

tralopyril11. Another major degradate, debrominated CL 322,250 (CL 322,248), is formed under 

anaerobic conditions (representing bottom sediment) and in saltwater conditions and did not 

degrade12. The study results may be seen in Table 17. 

Degradation of parent tralopyril produces compounds of different chemical and physical 

properties. The degradates have lower molecular weight, higher water solubility, 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 molecular 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 19).

Parent tralopyril and its degradates are expected to be present in both the water and sediment 

compartments in water bodies. Parent tralopyril will continually leach and any organisms 

present will be exposed to the parent compound and 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, and the lack of water exchange because of a low 

flushing rate in some cases. However, the sorption based on suspended sediment in marinas is 

likely to reduce these water concentrations13. 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 bioconcentration in fish study (MRID 48680501) for parent 

tralopyril which has not been formally reviewed but will be reviewed in Registration Review. 

The study reports bioconcentration factors (BCFs) 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 pKa 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 maximum expected environmental concentration (EEC)

and toxicity endpoints for avian species, fish, invertebrates, estuarine/marine species, sediment 

dwelling species, and plants to generate risk 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 tralopyril), 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 ). Terrestrial bird, mammal, or plant exposure 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 tralopryil and degradates through feeding were 

 

11 MRIDs 45673908, 45673909, 45673910, 45673911, 45673912

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 Effects Division, Guidance for Determining Pesticide Residues of Concern in 

Drinking Water in Coordination with the HED ROCKS )
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 24 of 69

assessed based on avian concerns when compounds similar to tralopryil are used in agricultural 

fields.

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 pesticide residues have the potential to reach the habitat of 

aquatic organisms, it is necessary to determine the risk to aquatic fish, invertebrates, and plants 

that may occur from parent tralopyril and its degradates. An ecological conceptual model 

summarizing exposure pathways for tralopyril and its reaction products/degradates is provided in 

Figure 1.

In Figure 1 all lines for leaching of parent tralopyril and its metabolites are solid, indicating that 

environmental exposure is expected to occur primarily from parent tralopyril and the 

degradate/metabolite CL 322,250. The lines representing exposure from down-the-drain 

exposure leading into wastewater treatment plants (WWTPs) are dashed because all paints 

containing tralopryil are solvent based (not water based) and cannot be released into a 

wastewater treatment plant15. Exposure to total tralopyril residues (parent and degradates) will 

occur in both water and sediment16. In addition, the degradate debrominated CL 322,250 (CL 

322,248) is expected to be present in anaerobic (representing sediment) and in saltwater 

conditions17. 

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 treated boats can be used in 

both freshwater and saltwater. Leaching of tralopyril (parent and CL 322,250) from 19 

antifoulant paints in salt water (Table 20) was observed at maximum rates of 2.2-48 

ug/cm2/day18. However, the registrant assumed a leaching rate of 4 ug/cm2/day for the parent 

compound in freshwater in the risk assessments contained in MRIDs 47250101 and 47301601. 

Based on this assumed parent leaching rate (4 ug/cm2/day), the registrant-calculated leaching 

rates for the CL 322,250 and CL 322,248 degradates of 3.84 and 3.456 ug/cm2/day. These 

degradate leaching rates were based on the maximum percent formation of 96 and 86 % in the 

environmental fate studies19. When compared to the actual maximum leaching rates (19 total), 

the assumed fresh water leaching rate of 4 ug/cm2/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 extent of leaching and ecological and drinking water 

exposure using the 4 ug/cm2/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-2013-0217

www.regulations.gov

Page 25 of 69

Figure 1 – Conceptual Model for Ecological Exposure and Effects of Tralopyril to Aquatic 

Organisms from the Antifoulant Use

4.2 Ecological Effects Assessment

The ecological effects assessment evaluates the potential for adverse effects 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 survival, reproduction, and growth of terrestrial 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 invertebrates, small mammals, benthic freshwater and marine/estuarine 

invertebrates, algae, and terrestrial plants. 

Acute (short-term) and chronic (long-term) toxicity information was characterized based on 

registrant-submitted studies. A summary of the available ecotoxicity information are provided in 

this preliminary work plan. Table 13, Table 14, and Table 15 summarize the most sensitive 

ecological toxicity endpoints based on an evaluation of the submitted studies. 

4.2.1 Mode of Action

The mode of action is being reviewed to determine if a total toxic residue approach will be taken.

4.2.2 Measures of Effect (Ecotoxicology Assessment Endpoints)

Current selected ecotoxicological endpoints are summarized in Table 13, Table 14, and Table 15. 

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-2013-0217

www.regulations.gov

Page 26 of 69

Table 13 – Selected Effects Endpoints for the Ecological Risk Assessment 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

LD50 = 24.7; 

NOEL = 6 

(mg ai/kg-bw)

Acceptable MRID 

43492809

Mallard Duck (Anas 

platyrhynchos)

Subacute 

(Dietary) 10-Day

LC50 = 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

LC50 = 1.3; 

NOEC = 0.68

(μg a.i./L)

Acceptable MRID 

46596002

Chronic1 Data Gap: Early life stage with Rainbow Trout 

(Oncorhynchus mykiss) or Acute Zebra Fish1(Danio rerio)

Aquatic Animals: 

Freshwater 

Invertebrates

Water Flea (Daphnia 

magna)

Acute 48-Hour EC50 = 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 LC50 = 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 LC50 = 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 EC50 = 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 

plumulosus)

Chronic

Not Anticipated to be Needed for Parent: In 

Estuarine/Marine environment the parent is highly 

unstable, data with stable degradate are anticipated to be 

needed 

Aquatic Plants: 

Non-Vascular

Marine Diatom 

(Skeletonema 

costatum)

Non-listed 96-hour IC50 = 2.7; 

Acceptable MRID 

46619901 Listed 96-hour NOAEC = 1.5

μg/L 

Aquatic Plants: 

Vascular

Duckweed (Lemna 

gibba)

Non-listed 7-day IC50 = 87.2 μg

a.i./L Acceptable MRID

45674116 Listed 7-day NOAEC = 22 

μg a.i./L
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 27 of 69

Receptor Group Surrogate Species Risk Scenario Study 

Duration

Toxicity 

Endpoint Classification Reference

Aquatic Rooted 

Plant Rice (Oryza sativa)

Seedling 

Emergence

Non-listed

14-day IC25 = 170 μg

a.i./L Acceptable MRID 

45674115

Listed 14-day NOAEC >

170 μg a.i./L

Terrestrial 

Mammal Rat

Acute (Oral) N/A LD50 = 27.0 

mg/kg2 Acceptable MRID 43492824

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 fish 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 acute value to estimate a rainbow trout chronic value.

2 To asses risk to terrestrial animals ingesting water or food contaminated with econea a value from available data 

will be used as a surrogate. 

Table 14 – Selected Effects Endpoints 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 

platyrhynchos)

Subacute 

(Dietary) 11-Day

LC50 = 962; 

NOAEL = 250 

(mg/kg diet)

Acceptable MRID 

46596013

Aquatic Animals: 

Freshwater Fish

Rainbow Trout 

(Oncorhynchus 

mykiss)

Acute 96-Hour

LC50 = 520; 

NOAEC= 320

(ppb) 

Acceptable/

updated from 2007 

risk assessment

MRID 

46596010

Chronic1 ELS Data Gap: Early life stage with Rainbow Trout 

(Oncorhynchus mykiss)

1

Aquatic Animals: 

Freshwater 

Invertebrates

Water Flea 

(Daphnia magna)

Acute 48-Hour

EC50 = 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

LC50 > 950; 

NOEC ≥ 950

(ppb)

Supplemental/

For purposes of the 

risk assessment, the 

non-definitive LC50

value will be used 

as the LC50 value2. 

MRID 

45674101

Chronic 34-Day NOAEC = 240 

ppb Acceptable MRID 45674106
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 28 of 69

Receptor Group Surrogate Species Risk

Scenario

Study 

Duration

Toxicity 

Endpoint 

Classification/ 

Comments Reference

Aquatic Animals: 

Marine/Estuarine 

Invertebrates

Mysid

(Americamysis 

bahia)

Acute 96-Hour

LC50 = 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

EC50 = 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 

plumulosus) 

Chronic

Data anticipated to be required. In seawater parent is not 

expected to be stable. CL322,250 is expected to be the 

compound present in sediments in seawater given its stability 

and Kd, Kow. No chronic reproduction data are available.

Aquatic Plants: 

Non-Vascular

Marine Diatom 

(Skeletonema 

costatum)

Non-listed 96-hour IC50 = 660

ppb Acceptable MRID 

46596014 Listed 96-hour NOAEC = 500 

ppb

Aquatic Plant: 

Vascular

Duckweed (Lemna 

gibba)

Non-listed 7-day IC50 > 990 ppb Supplemental—

parent value will be 

used to conduct risk 

assessment

MRID 

45674122 Listed 7-day NOAEC = 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 N/A LD50 = 2500 

mg/kg Acceptable MRID 43492826

Chronic N/A

Not anticipated to be required. Exposure not 

anticipated to be of chronic concern because 

neither parent nor degradate are expected to 

bioaccumulate. 3

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 test, or submittal of a zebra fish acute study to use in 

calculating a rainbow trout chronic NOAEC using an existing and acceptable zebra fish ELS test and an acute-tochronic ration (ACR) from the zebra fish data, or if no data are submitted, data from the parent will be used as a 

surrogate.

2 Without a definitive acute LC50 or an acceptable limit test, risks may over estimated.

3 Based on Bioconcentration factors (BCFs) of <32X (Level of concern is 1000X) [MRID 48680501].
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 29 of 69

Table 15 – Selected Effects Endpoints 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 

platyrhynchos)

Subacute 

(Dietary) 8-day

LC50 > 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.

Chronic1 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 LC50 > 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 LC50 = 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-2013-0217

www.regulations.gov

Page 30 of 69

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 IC50 > 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 IC50 > 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 IC50 > 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 hazard and risk characterization 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 Norfolk Harbor/James River (Virginia) were used 

as inputs for running these models. The model simulations were used to estimate the 

concentrations of CL322,250 and CL 322,248 in the above harbor systems. The outputs from the 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 31 of 69

MAMPEC runs from the Barbours Point (Houston) were used for ecological risk assessment of 

tralopyril. This assessment was focused on large ships only. The Agency has since developed a 

fresh water lake scenario for use of antifoulants. The Agency will reassess the fresh- and 

saltwater exposure and risk to non-listed and listed species. The 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 required 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 numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its 2008 reregistration decision for tralopyril, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p), tralopyril is subject to 

the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

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

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

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

of chemicals identified for EDSP screening was published on June 14, 201320 and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors. 

 

20 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 32 of 69

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.21

6 Optional Label Changes 

As discussed in Section 3.1.1., the Agency recommends that labels be revised to indicate that full 

face respirators with organic vapor removing cartridges and P-100 prefilters be required for 

spray applications.

7 Next Steps

A DCI will be developed regarding the data needs listed under Table 8 “Studies Anticipated as 

Needed for the Registration Review of Tralopyril” of this document. The agency expects to issue 

the DCI in December 2014.

8 References 

Best, S.; McGuire, G. (1999) Identification of Unknown Component Present in a Day 30 Surface 

Water Following Application of (Carbon-14)-R107894 to Loamy Sand Sediment: Lab 

Project Number: 17802: 16787: 367605. Unpublished study prepared by Inveresk 

Research. 34 p. 45673912

Cafarella, M. (2005) R107894 - Acute Toxicity to Water Fleas, (Daphnia magna) Under FlowThrough Conditions. Project Number: 13751/6144, AGR/921. Unpublished study 

prepared by Springborn Smithers Laboratories. 66 p. 46596001.

Cafarella, M. (2005) R107894 - Full Life Cycle Toxicity 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

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 Smithers 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 Springborn Smithers Laboratories. 81 p. 46596011

Cafarella, M. (2005) CL322,250 - Life Cycle Toxicity Test with Mysids (Americamysis bahia). 

Project Number: 13751/6153, AGR/927. Unpublished study prepared by Springborn 

Smithers Laboratories. 87 p. 46596012

 

21 http://www.epa.gov/endo/
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 33 of 69

Cafarella, M. (2006) R107894 - Acute Toxicity to Eastern Oyster (Crassostrea virginica) Under 

Flow-Through Conditions. Project Number: 13751/6157, AGR/1176, 

TS/FT/OYSTER/R107894. Unpublished study prepared by Springborn Laboratories Inc. 

70 p. 46751305

Cox, P.; Ristorcelli, D. (2001) R107894: Determination of the Physico-Chemical Properties (pH, 

pKa, and EC Tests A4, A6 and A8): Final Report: Lab Project Number: 1073/41-D2141: 

AGR 00301. Unpublished study prepared by Covance Laboratories, Ltd. 59 p. MRID 

45673906.

Deltares Software. 2012. MAMPEC 3.0 model. 

http://www.deltares.nl/en/software/1039844/mampec/1232321

Dionne, E. (2001) CL322.250--Acute Toxicity to Eastern Oysters (Crassostrea virginica) Under 

Flow-Through Conditions: Lab Project Number: 13751.6123: AGR 364: 

031301/FIFRA/OPPTS/FT-OYSTER. Unpublished study prepared by Springborn 

Laboratories, Inc. 71 p. {OPPTS 850.1025} 45674103

Durando, J. (2005) Primary Eye Irritation Study in Rabbits: R107894. Project Number: P324, 

17342. Unpublished study prepared by Product Safety Laboratories. 17 p. 46539401

Gallagher, S.; Martin, K.; Beavers, 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.; Beavers, 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.; Beavers, 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

Garrod, Ani, R. Guiver, and D.A. Rimmer. Year??? Potential Exposure of Amateurs 

(Consumers) through Painting Wood Preservative and Antifoulant Preparations. Annals 

Occupation Hygiene, 44(6), pp. 421-426. MRIDs 46244421 and 47307308)

Hall, T.; Donald, E. (2001) R107894 Technical: Acute Oral Toxicity (Fixed 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: Acute Dermal Toxicity (LD50) Test in Rats: 

Lab Project Number: 19836: 577470. Unpublished study prepared by Inveresk Research. 

37 p. {OPPTS 870.1200} 45673916
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 34 of 69

Hawkins, W.; Donald, E. (2002) R107894 Technical: Buehler Test in Guinea Pigs for Delayed 

Skin Sensitisation Potential: Lab Project 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 Springborn Laboratories, Inc. 74 p. {OPPTS 

850.4400} 45674116

Hoberg, J. (2001) CL322,250--Toxicity to Duckweed, Lemna gibba: Lab Project Number: 

13751.6108: AGR 338. Unpublished study prepared by LISEC. 70 p. {OPPTS 850.4400} 

45674122

Hoberg, J. (2001) CL 322,248--Toxicity to Duckweed, 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 Freshwater Diatom, Naviculla pelliculosa: Lab 

Project Number: 13751.6135: AGR 479: EC/OPPTS/SA-NAVICULA. Unpublished 

study prepared by Springborn Smithers Laboratories. 70 p. {OPPTS 850.5400} 

45893904

Hoberg, J. (2005) R107894- Acute Toxicity to the Marine Diatom, Skeletonema costatum, Under 

Static Conditions. Project Number: 13751/6147, 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 Number: 13751/6154, AGR/1027. Unpublished study 

prepared by Springborn Smithers 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

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 R107894 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
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 35 of 69

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 Laboratories, 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. Unpublished study prepared by Springborn 

Laboratories, Inc. 62 p. {OPPTS 850.1075} 45674101

Mackie, J. (1997) Determination of the Hydrolytic 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 prepared by Inveresk Research. 122 p. 

45673913

Mackie, J. (1999) Adsorption/Desorption of the 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

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 Hydrolytic Degradation Products of (Carbon-14)-R107894: Lab 

Project Number: 15365: 364871: 15348. Unpublished study prepared by Inveresk 

Research. 37 p. 45673909
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 36 of 69

Moore, G. (2006) Acute Inhalation Toxicity Study in Rats - Limit Test: R107894. Project 

Number: 19437, AGR/1269, P330. Unpublished study prepared by Product Safety 

Laboratories. 22 p. 46846601

Putt, A. (2001) CL 322,250--Acute Toxicity to Mysids (Americamysis bahia) Under FlowThrough Conditions: Lab Project Number: 13751.6121: AGR 370. Unpublished study 

prepared by Springborn Laboratories, Inc. 62 p. {OPPTS 850.1035} 45674104

Putt, A. (2005) R107894 - Acute Toxicity to Rainbow Trout (Oncorhynchus mykiss) Under 

Flow-Through Conditions. Project Number: 13751/6143, AGR/920. Unpublished study 

prepared by Springborn Smithers Laboratories. 67 p. 46596002

Putt, A. (2005) CL322,250 - Acute Toxicity to Rainbow Trout (Onchorynchus mykiss) Under 

Flow-Through Conditions. Project Number: 13751/6150, AGR/924. Unpublished study 

prepared by Springborn Smithers Laboratories. 69 p. 46596010

Ristorcelli, D. (2001) R107894: Determination of the Physico-Chemical Properties: Final 

Report: Lab Project Number: 1073/48-D2149: 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. Project Number: 13751/6159, AGR/1178, 

PPTS/SHM/STA/JANSSEN. Unpublished study prepared by Springborn Laboratories 

Inc. 60 p. 46751309

Sayers, L. (2006) CL322,248 - Acute Toxicity to Mysids (Americamysis bahia) under Static 

Conditions. Project Number: 13751/6160, AGR/1179, PTS/MYSID/ST/JANSSEN. 

Unpublished study prepared by Springborn Laboratories Inc. 62 p. 46751308

Serak, K.; Hanh, J. (2006) Determination of the Leach Rate of Econea from Paint (International 

Copper Free) in Synthetic Seawater. Project Number: 49702, 49702/7. Unpublished study 

prepared by Analytical Bio-Chemistry Labs., Inc. 62 p. 46934508

Serak, K. (2007) Determination of the Leach Rate 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
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 37 of 69

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 ECO 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 ECO Antifouling Paint 1604 

Red: Final Report. Project Number: 390/102. 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 Determination of Armor Solventbase Antifouling Paint: 

Final Report. Project Number: 260/10. Unpublished study prepared by Case Consulting 

Laboratories, Inc. 37p. 49046003

Sousa, J. (2001) R107894--Early Life-Stage Toxicity Test with Sheepshead Minnow 

(Cyprinodon variegatus): Lab Project Number: 13751.6128: AGR 383. Unpublished 

study prepared by Springborn Laboratories, Inc. 84 p. 45674007

Sousa, J. (2001) CL 322,250--Early Life-Stage Toxicity Test with Sheepshead Minnow 

(Cyprinodon variegatus): Lab Project Number: 13751.6129: AGR 385. Unpublished 

study prepared by Springborn Laboratories, Inc. 83 p. 45674106

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, Inc. 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 Rate 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
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 38 of 69

Tunink, A. (2010) Determination of the Leach Rate 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://chemistry.tutorvista.com/physicalchemistry/van-der-waals-equation.html

U.S. Center for Disease Control. 2013. National 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/publications/OPPTS_Harmonized/850_Ecological_Ef

fects_Test_Guidelines/Drafts/850-1730.pdf

U.S. Environmental Protection Agency (EPA). 2002. ECOTOX User Guide: ECOTOXicology 

Database System. Version 3.0. Available: http://www.epa.gov/ecotox/

U.S. Environmental Protection Agency. 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)

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.

U.S. Environmental Protection Agency. 2008. An AD Memo from Talia Lindheimer to Marshall 

Swindell on “Acute and Chronic Drinking Water Exposure and Risk Assessment for the 

Registration Action of tralopyril (EPA Reg. #2693-200)”, April 16, 2008.

U.S. Environmental Protection Agency. April 10, 2008. Residential Exposure and Risk 

Assessment of the End Use 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-(trifluoremethyl), as an Antifoulant in Paint for Pleasure 

Craft and Do-it-Yourself Applications, D384689.

U.S. Environmental Protection Agency. May 10, 2011. Environmental Fate and Effects 

Division Guidance, Author, Don Brady. Guidance for Determining Pesticide Residues of 

Concern in Drinking Water in Coordination with the HED ROCKS. 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 39 of 69

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/exposure/pubs/episuitedl.htm 

U.S. Environmental Protection Agency. December 2012. Registration Review Process. 

http://www.epa.gov/oppsrrd1/registration_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/lawsguidance/cwa/tmdl/listing.cfm

Van der Kerken, K. (2002) Alga, Growth Inhibition Test Effect of CL 322,248 on the Growth of 

Skeletonema costatum: Final Report: Lab Project Number: AGR 00309: WE-06-272: 

KV-2001-10532-R-MJ-WE06272. Unpublished study prepared 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 Environments: Final Report. 

Project Number: WEI/567/01/F, JANSSEN/AGR/3762. Unpublished study prepared by 

Waterborne Environmental, Inc. (WEI). 28 p. 47301601

Yang, H. (2000) Validation of the Ion Chromatographic Method M-3417.01 to Assay for 

Triethylamine (TEA) in the CL 303268 Technical 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.
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 40 of 69

Appendix A Toxicology Profile

Acute Toxicity for Product Labeling 

As summarized in Table 16, in acute toxicity studies, tralopyril has been shown to have severe 

toxicity by the oral route (Toxicity Category I), moderate toxicity by inhalation route (Toxicity 

Category II) and weak toxicity through dermal route (Toxicity category III). Tralopyril is a mild 

skin irritant (Toxicity Category IV) and a mild eye irritant (Toxicity Category III). Tralopyril is 

not a dermal sensitizer.

Table 16 – Acute Toxicity Data for Tralopyril

Guideline 

No.

Data Requirement/ 

Species

Conclusions/Acceptable/ 

Comments

Tox

Cat

MRID

870.1100 Acute Oral/Rat LD50 = Not established 

[Acceptable/-Guideline]

I 45673915

870.1200 Acute Dermal/Rabbit LD50 >2000 mg/kg for both males and 

females 

[Acceptable/Guideline]

III 45673916

870.1300 Acute Inhalation/Rat* LC50 = <510 mg/m3(males)

LC50 = <510 mg/m3(females)

LC50 = <510 mg/m3(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 summary 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 (OPPTS 870.3100). During this study tralopyril (94.6% 

a.i) was administered to 10 Sprague-Dawley rats/sex/dose via food at dose levels of 0, 80, 250, 

or 750 ppm active ingredient. These concentrations were equivalent to 5.2, 16.2, or 51.9 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 41 of 69

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-Dawley 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 these rats was similar to that observed 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 course of the study. There were no treatment -

related clinical signs of toxicity, ophthalmological findings, urinalysis, 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% difference from controls) effects in high-dose 

animals, except for a 15% increase in platelets in the males with a corresponding increase in 

females that was not significant (9%). All hematological values were comparable to controls 

after the 4-week recovery period. Alanine aminotransferase (ALT) and alkaline phosphatase 

(ALP) were statistically-significantly increased in the mid- and high-dose males, which correlate 

to increased relative liver weights in the main group. Females displayed a lesser increase in ALP 

with only the high-dose group demonstrating a statistically significant change. Low-dose males 

also displayed a statistically significant increase in ALP. Signs of dehydration and 

undernourishment were evident with 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 group indicate reversibility 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 weights of several organs. 

treatment-related changes include increases in relative brain weights (mid- and high-dose males; 

high-dose females) and liver weights (mid- and high-dose males; all treated females). However, 

the changes in ALP and ALT enzyme were reversible after 4 weeks and the increases in the liver 

were likely due to increased metabolism of the test 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 effects were noted in the brain at necropsy in these 

recovery group animals. 

Microscopic findings of the brain 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; moderate 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 females as well as the low-dose females. 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 42 of 69

Microscopic finding of the brain and spinal cord of the animals that were in the perfusion 

fixation satellite group displayed treatment-related finding which included slight to moderate 

vacuolization. The lumbar region (cauda equina) was most profoundly affected and the females 

appeared to be more sensitive. 

Other treatment-related microscopic 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 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 root 

fibers). Peer review of the pathology confirmed the general findings, although there were some 

minor differences on severity and in some instances the involvement of vacuolation in several 

tissues. 

There were no changes in behavior or parasympathetic movements (e.g. tremors, convulsions, 

impaired gait, posture, response to handling, activity, or arousal).

After 4 weeks of no treatment, microscopic lesions were still observed in the brain and lumbar 

region. Minimal multifocal vacuolization of the brain 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, hematology, 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 and 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 (OPPTS 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 subchronic study. Treatment-related effects at 1000 

mg/kg/day included ano-genital staining but this was not considered to be toxicologically 

significant. There were no mortalities during this study. Additionally, there were no significant 

changes to body weight, food consumption, food efficiency, organ weight, or pathology (gross or 

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

Based on these results, rats were be expected to tolerate an exposure of >1000 mg/kg/day in the 

subsequent 90-day dermal study. 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 43 of 69

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 days/week during a 90-day period. One 100-

mg/kg/day female died prior to study termination. A treatment-related dose-dependent increase 

in small dermal sores was noted in both the 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 guidelines (OPPTS 870.3465, 870.6200). During this study 

tralopyril (92.4% a.i.) was administered via nose-only exposure to 10 Sprague Dawley rats per 

sex and air concentration in Phase I and 12 rats per sex and air concentration in Phase II. The air 

concentrations (both nominal and analytical) were 0, 20, 40, and 80 mg/m3. The exposure period 

was 6 hours per day, 7 days per week for a minimum of 90 consecutive days. The particle size 

was within the accepted range.

The No Observable Adverse Effect Level (NOAEL) was 20 mg/m3for survival, hematology, 

clinical chemistry, or gross pathology. Nasal lesions were observed in the 20 mg/m3 animals and 

were considered a local effect.

One female rat in the Phase I inhalation toxicity was found dead on study Day 9. This animal 

was in the control group, therefore the death was not considered test article-related. Three males 

in the 80-mg/m3Phase II neurotoxicity study group were found dead on study Days 0, 20, and 

85, respectively. Additionally, an 80 mg/m3female 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/m3group these deaths were considered test article-related. 

Clinical signs of toxicity related to treatment included brown staining on multiple body surfaces 

in males and females of all three test article-treated groups. Staining, which began on Day 11 

and persisted through the end of the study, was observed on the neck, forelimb, abdominal area, 

thoracic area, inguinal area, hindlimb, rump, anogenital area, urogenital area, and tail. Reduced 

mean body weights for the male and female animals of the 20- (males), 40-, and 80-mg/m3test 

groups were statistically significantly 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 localized in the dorsal region of the nose, and included inflammation, 

ulceration or erosion, squamous or respiratory metaplasia, and olfactory or respiratory epithelial 

degeneration. These changes displayed a dose-related increase in incidence and severity. 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 44 of 69

In the Phase I of the study, the LOAEL was 20 mg/m3for male and female is 20 mg/m3based on 

the findings observed in the N1 (Nasal section 1) for both sexes and N3 section in the females of 

the 20-mg/m3 animals. The 20-mg/m3 males exhibited chronic and subacute inflammation, 

ulcerations (N1), and exudate (N1), and the females had subacute inflammation (N1), epithelial 

hyperplasia (N1), hyperkeratosis (N1), and degeneration of olfactory epithelium (N3) and 

decrease body weight gain in male. The NOAEL could not be determined (<20 mg/m3)(LDT). 

In the phase II of the study, neurobehavioral assessment (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 animals/sex/dose in the controls and 80-mg/m3groups were 

perfused in situ for neuropathological examination of the central and peripheral nervous system 

tissues. For the Phase II neurotoxicity study, after the first day of exposure, 1 male and 1 female 

were found dead in the 80 mg/m3 group and were replaced. Two 80 mg/m3 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/m3animals were observed to have soiled 

fur, unclean fur, and increased grooming (80 mg/m3 males) during Weeks 7 and 12. These 

changes correlate with the clinical toxicity findings of soiled fur and were not considered adverse 

neurotoxicological findings. During Week 3 FOB measurements, an overall decrease in total 

locomotor activity was noted in the 40 and 80 mg/m3 males and in ambulatory activities for 80 

mg/m3 males as a result of reduced activity in sub-session measurements. During Week 12, the 

80 mg/m3 males were observed with total activity decrease compared to controls. 

At neuropathology, an increase in minimal axonal degeneration was observed in the peroneal 

nerve in the 80 mg/m3 animals (3/6 for both males and females) over controls (0/0 for both males 

and females). 

The neurotoxicity LOAEL was 40 mg/m3in males based on decreased motor activity and 80 

mg/m3in females based on axonal degeneration observed in the peroneal nerve. The 

neurotoxicity NOAEL was 20 mg/m3for males and 40 mg/m3 for females.

Developmental Toxicity 

There is one rat developmental study in the tralopyril toxicology database. Since drinking water 

exposure can occur if tralopyril antifoulant paints are used on fresh water boats or ships, an 

additional developmental toxicity 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 in D312232 (not yet finalized) and it was found to be acceptable under 

the relevant guideline for a developmental toxicity study in rats (OPPTS 870.3700; OECD 414). 

During this study, tralopyril (94.6% a.i.) was administered to 25 time-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). 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 45 of 69

Treatment related maternal effects at 20 mg/kg/day included increased mortality, frequent 

salivation, reduced body weight gain, decreased uterine weight, decreased corrected body weight 

gain, increased resorptions (total, early and late) and decreased placental weight. At 10 

mg/kg/day, dams exhibited frequented salivation. The maternal LOAEL is 10 mg/kg/day, based 

on frequent salivation. The NOAEL is 5 mg/kg/day.

Developmental findings also occurred at 10 and 20 mg/kg/day. Treatment-related effects at 20 

mg/kg/day included decreased mean fetal weight and an increased incidence of fetuses exhibiting 

disturbances and delays of ossification (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 maternal toxicity and correlated 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 fetal 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 antifoulant 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 (Bone Marrow Micronucleus), 

There is no in vitro Salmonella typhimurium Reverse Mutation Assay in the toxicology database 

and is considered as a data gap to evaluate the mutagenic potential of tralopyril. 

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

Chinese hamster ovary (CHO) cells were exposed to tralopyril (94%) in dimethylsulfoxide 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 response. There was no evidence of 

a concentration-related, positive response that induced mutant colonies over background. This 

study is classified as ACCEPTABLE-GUIDELINE and satisfies the guideline requirement 

(OPPTS 870.5300, OECD 476) for in vitro mutagenicity (mammalian forward gene mutation) 

data.

In vivo Mammalian Cell Cytogenetics Assay (MRID 46426904)
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 46 of 69

Five 5 male mice per dose were exposed once by oral 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 animals tested in the main assay, however, clinical 

signs of toxicity (squatting posture) were observed in the 12 mg/kg bw animals at both 24- and 

48-hour harvest times. No statistically-significant 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 control elicited a clearly 

positive response. There was no significant increase in the frequency of micronucleated 

polychromatic erythrocytes in bone marrow after any treatment time. This study is classified as 

ACCEPTABLE-GUIDELINE and satisfies the guideline 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 spinal 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 root fibers). After 4 weeks of no treatment, 

microscopic lesions were still observed in the brain and lumbar region. 

2. Decreased motor activity and axonal degeneration in the peroneal nerve were observed in 

the 90-day rat inhalation study (MRID 46802202).

3. Frequent salivation was identified as a significant effect in the rat developmental study 

(MRID 46426902).
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 47 of 69

Appendix B Environmental Fate

Parent tralopyril and its degradation products can create environmental 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 will not be assessed in this document. Aquatic 

exposure will be highest in marinas and around docks where boats are stored, and lower outside 

marinas where boat density is lower. and therefore long-term acute and 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 hydrolysis22 and photodegradation 

in water,23 and by biotic processes24 to form CL 322,250, which is defluorinated parent 

compound with a carboxylic acid group. Hydrolysis half-lives for 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 formally reviewed and will be in registration 

review. Aquatic exposure in freshwater will occur from the parent compound and the more 

persistent CL 322,250 degradate under acid to neutral conditions. Under alkaline freshwater and 

in saltwater conditions, the primary exposure will be from the CL 322,250 degradate. The halflives for parent tralopyril in anaerobic conditions were 29 and 0.7 days in freshwater and 

saltwater, and were 12 and 0.6 days under aerobic conditions. The half-lives for CL 322,250 

were 23-31 days in these conditions and were longer than for parent 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 17). 

Degradation of parent tralopyril produces compounds of different chemical and physical 

properties. The degradates have lower molecular weight, higher water solubility, and lower log 

Kow (Log P) values25. Therefore, the degradates would be expected to be present in water with 

a higher water:sediment ratio than parent tralopyril. Based on the molecular weights, vapor 

pressures, Henry’s Law constants, and study results26, neither parent tralopyril nor its degradates 

are expected to volatilize from water (Table 19).

Sorption to sediment is a significant route of dissipation (disappearance) for tralopyril and its 

degradates/metabolites. For parent tralopyril 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 sorption for the freshwater and saltwater sediments was 96-98 and 82-

 

22 MRIDs 45673908, 45673909

23 MRID 47128801

24 Aquatic metabolism, MRIDs 45673910, 45673911, 45673912

25 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, lowering the predicted log P.

26 MRIDs 45673910, 45673911, 45673912, EPI-Suite 4.1
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 48 of 69

97 %, respectively. For CL 322,250, the sorption for the freshwater and saltwater sediments was 

96-98 and 57-95 %, respectively27 . However, the total sorption to sediment in the aquatic 

metabolism studies28 did not exceed 70 %. In the anaerobic aquatic metabolism study29, the total 

sorption (extractable plus unextractable residues) was 70 and 37 % for the freshwater and salt 

water systems, respectively. In the aerobic aquatic metabolism study,30 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 explained by the water to sediment ratios in the 

studies, the use of shaking in the leaching-adsorption-desorption studies (standard practice), and 

degradation to other compounds. In the leaching-adsorption-desorption studies31, 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 studies32 was 10:1. The main reasons for the apparent differences in study results 

lies in the fact that a lower water: sediment ratio forces higher sorption of a pesticide to the 

sediment33. Shaking of the water and sediment in the leaching-adsorption-desorption study 

(OCSPP 835.1230) to achieve sorption is also standard, while shaking is not used in metabolism 

studies because the shaking can enhance degradation over the long-term34. Also, the degradation 

in the aquatic metabolism studies formed compounds that are more polar because of loss of 

halogen molecules (fluorine, bromine)35. As a result, further degradation of the parent 

compound and CL 322,250 results in more water solubility (based on EPI-Suite 4.1) and lower 

sorption (Table 18 and Table 19). The Koc values (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 18). In the aquatic metabolism studies36, 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/cm2/day. Average and 

cumulative leaching rates ranged from 1.3-22 ug/cm2/day and 55.5-986 ug/cm2, respectively 

(Table 20).

Bioconcentration in fish and aquatic invertebrates is also possible. There was a submitted 

bioconcentration in fish study37 for parent tralopyril in carp that indicates limited 

bioconcentration factors (BCFs) of 3.2-32 depending on the treatment concentration. However, 

that study has not been formally reviewed and no conclusions can be drawn at this time. It will 

be reviewed in registration review. 

 

27 MRIDs 45673913, 45673914, Table 16

28 MRIDs 45673910, 45673911, 45673912

29 MRID 45673910

30 MRIDs 45673911, 45673912

31 MRIDs 456734913, 45673914

32 MRIDs 45673910, 45673911, 45673912

33 835.1230 test guideline, http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0006

34 OCSPP 835.4300 and 835.4400

35 http://chemistry.tutorvista.com/physical-chemistry/van-der-waals-equation.html

36 MRIDs 45673910, 45673911, 45673912

37 OCSPP 850.1730, MRID 48680501
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 49 of 69

Table 17 – Summary of parent tralopyril half-lives and degradate amounts and half-lives in 

environmental fate studies 

Study Type MRID Parent Half-lives (days)

Maximum formation % based on applied parent 

compound1,2 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 oC - 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 oC- 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 degradate7

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 degradate7

Degradate not 

formed in the study

Aqueous 

Photolysis 

(835.2240)

47128801 25 oC - 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 d1,2

(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 oC) -

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 degradate7

35.7 % (364 d)1

Saltwater system (21 oC) -Nonlinear half-life of 0.7 d25 % (7 d)

(half-life of 22 

days)

7.1 % (3 d), 

0.8 % (364 d)1

Minor degradate7

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 oC) -

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 degradate7

Degradate not 

formed in the study

Saltwater system (21 oC) -Nonlinear half-life of 0.6 d36-47 % 

(21-30 d)1,2

(half-life of 23 

days)

1.9% (30 d)130.3 % (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
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 50 of 69

5 CL 322,248 is debrominated CL 322,250

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

be stable

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

Table 18 – Sorption (Kf/Koc) of parent 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 19 – Physical-Chemical Properties for 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 m3

mol-1)

Reference

tralopyril 349.54

0.171(fresh 

water, pH 4.9)

0.16 (seawater, 

pH 8.1)

3.5 7.08 at 26 oC

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 3.722 None 7.62 x 10-75 x 10-8 EPI-Suite 4.1

CL 325,195 302.64 17.95 4.172 None 3.45 x 10-97.65 x 10-11 EPI-Suite 4.1

CL 322,248

(Debrominated 

CL 322,250)

248.67 476 1.682 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 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 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 requires the shaking of a flask containing n-octanol, distilled 

water, and the pesticide of interest. Water-soluble pesticides will preferentially partition to water instead of octanol because of 

increased hydrogen bonding.
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 51 of 69

Table 20 – Reviewed and Accepted Paint Leaching Studies for Tralopyril in Seawater

MRID

Paint

Ingredients (% 

w/w)

Temp 

(

oC)

CL 

322,250 1

measured?

Review 

Date

Results

Maximum, Minimum, and Average Units are 

ug/cm2/day and Cumulative Units are ug/cm2)

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

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
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 52 of 69

MRID

Paint

Ingredients (% 

w/w)

Temp 

(

oC)

CL 

322,250 1

measured?

Review 

Date

Results

Maximum, Minimum, and Average Units are 

ug/cm2/day and Cumulative Units are ug/cm2)

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
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 53 of 69

MRID

Paint

Ingredients (% 

w/w)

Temp 

(

oC)

CL 

322,250 1

measured?

Review 

Date

Results

Maximum, Minimum, and Average Units are 

ug/cm2/day and Cumulative Units are ug/cm2)

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
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 54 of 69

MRID

Paint

Ingredients (% 

w/w)

Temp 

(

oC)

CL 

322,250 1

measured?

Review 

Date

Results

Maximum, Minimum, and Average Units are 

ug/cm2/day and Cumulative Units are ug/cm2)

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

490460032 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

 All parent tralopyril residues were chemically converted to the degradate CL 322,250 in the studies for chemical 

analysis.

2

 MRID 49046003 was has not been formally reviewed but will be reviewed in Registration Review 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 55 of 69

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 grade of the active ingredient (TGAI) 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 for 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 21. 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 conducted on the CL325,195 metabolite of tralopryil. The 

results of testing are provided in Table 21. These results indicate that the CL325,195 degradate 

is slightly toxic to practically non-toxic to birds on an acute oral basis.

Two subacute dietary studies using the technical grade of the active 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 test species are mallard duck (a 

waterfowl) and bobwhite quail (an upland gamebird). Avian dietary testing with waterfowl was 

required for tralopyril technical and the two major 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 21. These results indicate that CL322,250 is highly toxic to 

waterfowl when ingested via food items. All avian subacute data requirements are fulfilled for 

the parent and its two major degradates (CL322,250 and CL322,248).

Birds, Chronic

Avian reproduction studies using the technical grade of the active ingredient are anticipated to be 

required for tralopyril because the following conditions are met: (1) birds may be subject to 

repeated or continuous exposure to the pesticide, especially preceding or during the breeding 

season, (2) the pesticide is stable in the environment to the extent that potentially toxic amounts 

may persist in animal feed which also includes ingestion of water, and (3) the pesticide is stored 

or accumulated in plant or animal tissues (indicated by a Kow value of greater than 1000). Avian 

reproduction testing is required for the currently proposed uses of tralopyril.
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 56 of 69

Table 21 – Toxicity Profile of Tralopyril Parent and Degradates to Birds

Chemical MRID Test Species Study 

Duration Toxicity Endpoint Classification

Econea 

technical 46596005 Mallard Duck (Anas platyrhynchos)

11 D LC50 = 10.76 ppm

NOAEL = 5.62 ppm Acceptable

Econea 

technical 43492809 Northern Bobwhite (Colinus virginianus) 14 D

LD50 = 24.7;

NOAEL = 6 

(mg ai/kg-bw)

Acceptable

Econea 

technical 43492808 Mallard Duck (Anas platyrhynchos)

14 D

LD50 = 77 

NOAEL = 20 

(mg ai/kg-bw)

Acceptable

CL 

322,250 46596013 Mallard Duck (Anas platyrhynchos)

11 D LC50 = 962 ppm

NOAEL = 250 ppm Acceptable

CL 

322,248 46751310 Mallard Duck (Anas platyrhynchos)

8 D LC50 > 5620 ppm

NOAEL = 3160 ppm Acceptable

CL 

325,195 44452612 Mallard Duck (Anas platyrhynchos)

14 D

LD50 > 2250 

NOAEL > 2250 

(mg ai/kg-bw)

Acceptable

CL 

325,195 44452611 Northern Bobwhite (Colinus virginianus) 14 D

LD50 > 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 pattern and pertinent environmental fate 

characteristics. In most cases, rat or mouse toxicity values obtained from studies conducted to 

support data requirements for human health risk assessment substitute for wild mammal testing. 

The Agency uses LC50 values from acute oral mammalian studies and NOEC values from 2-

generation reproduction studies along with other mammalian data which may be used for risk 

characterization (e.g. dermal studies). These toxicity values are reported in Table 16.

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 22. These results indicate that tralopryil 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-2013-0217

www.regulations.gov

Page 57 of 69

Based on the patterns of toxicity seen in marine/estuarine 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 degradates were submitted, however, those studies 

were determined to be invalid and are therefore are not included. Freshwater fish acute toxicity 

testing with a coldwater species (Rainbow Trout) using degradate 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 Sunfish 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 parent, 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 tralopyril because the end-use product is expected 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 continuous or 

recurrent, and (2) aquatic acute LC50 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 tested, but other species may be used. However, if other species 

are used an acute test for the chronic tested species 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 22; while there 

are fish early life stage tests with zebra fish there are no corresponding acute 96-hr LC50 values 

which would allow calculation of ACR. Therefore, chronic data for the most acutely sensitive 

species is anticipated to be required but may be addressed by either an acceptable zebra fish 

acute study or a rainbow trout ELS study.

Table 22 – Toxicity Profile of Tralopyril Parent 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 LC50 = 1.300 ppb

NOAEC = 0.68 ppb Acceptable

Econea 

technical 46596003 Bluegill sunfish (Lepomis macrochirus)

96 hr LC50 = 3.2 ppb

NOAEC = 1.3 ppb Acceptable

CL 322,250 46596009 Bluegill sunfish (Lepomis 

macrochirus)

96 hr LC50 = 1200 ppb

NOAEC = 550 ppb Acceptable

CL 322,250 46596010 Rainbow trout 

(Oncorhynchus mykiss)

96 hr LC50 = 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
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 58 of 69

Freshwater Invertebrates, Acute—Parent and Degradates

A freshwater aquatic invertebrate toxicity test using the technical grade of the active ingredient is 

anticipated to be required to establish the toxicity of tralopyril to invertebrates. The preferred 

test species is Daphnia magna. Results of this test using the parent, tralopyril, are listed in Table 

23. The daphnid acute study (MRID #465960-01), was classified as supplemental due to 

unexplained low percent recoveries in the measured chemical analysis. The 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 highly toxic to aquatic invertebrates 

on an acute basis. 

A freshwater aquatic invertebrate toxicity 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 23. 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 indicate 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 because the end-use product is expected 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 continuous or recurrent, and 

(2) aquatic acute EC50 values are less than 1 mg/l for the parent and major degradate CL 

322,250. Preferred test species is Daphnia magna. Freshwater aquatic invertebrate 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 freshwater invertebrates. Results of this test are 

listed in Table 23.

These studies show that the parent compound and degradates can cause growth and reproductive 

effects in aquatic invertebrates, but the degradates are substantially less toxic than the parent 

compound.

Table 23 – Toxicity Profile of Tralopyril 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 EC50 = 1.5 ppb

NOAEC = 0.32 ppb Acceptable

Econea 

technical 46596004 Water flea (Daphnia magna)

21 days 

(LC)

NOAEC = 0.20 ppba

LOAEC = 0.57 ppb Acceptable

CL 325,195 45706902 Water flea (Daphnia 

magna)

48 hr EC50 = 3,510 ppb

NOAEC = 2,700 ppb Supplemental

CL 322,250 46596008 Water flea (Daphnia 

magna)

48 hr EC50 = 510 ppb

NOAEC = 250 ppb Acceptable

CL 322,250 45706903 Water flea (Daphnia 

magna)

48 hr EC50 = 1,630 ppb

NOAEC = 1,000 ppb Supplemental
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 59 of 69

Chemical MRID Test Species Study 

Duration Toxicity Endpoint Classification

CL 322, 250 45674102 Water flea (Daphnia 

magna)

48 hr EC50 = 700 ppb

NOAEC = 430 ppb Supplemental

CL 322,250 46596011 Water flea (Daphnia 

magna)

21 days 

(LC)

NOAEC = 300 ppba

LOAEC = 540 ppb Acceptable

CL 322,248 45674112 Water flea (Daphnia 

magna)

48 hr EC50 > 16,800 ppb

NOAEC = 11,800 ppb Supplemental

CL 322,248 45674113 Water flea (Daphnia 

magna)

21 days 

(LC) NOAEC > 1,370 ppbb

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 the 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 required for tralopyril because it is intended for direct 

application to the marine/estuarine environment. The preferred test species is sheepshead 

minnow. This testing is anticipated to be required for antifoulants. Summaries of the results of 

studies submitted with tralopyril and degradates are provided in Table 24. The results indicate 

that tralopryil parent is highly toxic to estuarine/marine fish 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 conducted using parent tralopyril, major degradate 

CL322,250, and minor degradate CL325,195. These data in Table 24 demonstrate that the parent 

compound and degradates are capable of impacting fish larval survival and growth. The

degradates are substantially less toxic than the parent compound.

Table 24 – Toxicity Profile of Tralopyril Parent 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 LC50 = 23.71 ppb

NOAEC = 10.0 ppb Acceptable

Econea 

technical 45674007 Sheepshead minnow (Cyprinodon variegatus)

34 d (ELS) NOAEC = 4.3 ppba

LOAEC = 8.7 ppb Acceptable
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 60 of 69

Chemical MRID Test Species Study 

Duration Toxicity Endpoint Classification

CL 325,195 45674013 Sheepshead minnow 

(Cyprinodon variegatus)

96 hr LC50 > 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 LC50 > 89,000 ppb

NOAEC > 89,000 ppb Acceptable

CL 322,250 45674101 Sheepshead minnow 

(Cyprinodon variegatus)

96 hr LC50 > 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 estuarine/marine invertebrates using the technical grade of the active 

ingredient (TGAI) was required for tralopyril because the end-use product is intended for direct 

application to the marine/estuarine environment and testing is required for its major degradate. 

The preferred test species are mysid shrimp and eastern oyster. Results of these tests are listed in 

Table 25. The results indicate that parent tralopryil is very highly toxic to estuarine/marine 

invertebrates on an acute basis. Estuarine/marine invertebrate acute toxicity studies using the 

degradates were also submitted. The results indicate that CL322,250 is highly toxic to 

estuarine/marine invertebrates on an acute basis, CL322,248 is moderately toxic to 

estuarine/marine invertebrates on an acute basis, and CL325,195 is slightly toxic to 

marine/estuarine invertebrates 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 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 continuous or recurrent, and (2) aquatic acute EC50 values are less 

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

Table 25.

Table 25 – Toxicity Profile of Tralopyril Parent 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)

EC50 = 0.56 ppb

NOAEC = 0.19 ppb Supplemental
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 61 of 69

Chemical MRID Test Species Study 

Duration Toxicity Endpoint Classification

Econea 

technical 46751305 Eastern oyster (Crassostrea virginica)

96 hr (shell 

deposition)

EC50 = 0.64 ppb

NOAEC = 0.29 ppb Acceptable

Econea 

technical 45674006 Mysid (Americamysis bahia)

96 hr LC50 = 0.98 ppb

NOAEC = 0.36 ppb Acceptable

Econea 

technical 45674009 Mysid (Americamysis bahia)

28 d (LC) NOAEC = 0.25 ppba

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)

EC50 = 14,000 ppb

NOAEC = 6,900 ppb Acceptable

CL 325,195 45674015 Mysid 

(Americamysis bahia)

96 hr LC50 = 12,250 ppb

NOAEC = 5,300 ppb

Acceptable

CL 322, 250 45674103 Eastern oyster 

(Crassostrea virginica)

96 hr EC50 = 310 ppb

NOAEC = 46 ppb Acceptable

CL 322, 250 45674104 Mysid 

(Americamysis bahia)

96 hr LC50 = 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 LC50 = 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 characteristics which indicate these chemicals are

expected to partition to sediment, and ecological effects information 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 water 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 26. However, these are not chronic reproduction tests. Tralopyril under 

acidic to neutral conditions is expected to predominate and be stable for greater than 10 days in 

freshwater environments and the major degradate CL 322,250 is expected to be stable in 

seawater conditions. Therefore chronic reproduction tests are anticipated to be required for the 

parent in freshwater and for the major degradate CL 322,250 in seawater. 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 62 of 69

Table 26 – 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)

LC50 = 2.2 mg/kg-sed

NOAEC = 1.0 mg/kg-sed Acceptable

Econea 

technical 45674011 Amphipod (Leptocheirus plumulosus)

10 D (sub 

chronic)

LC50 = 1.1 mg/kg-sed

NOAEC = 0.50 mg/kgsedAcceptable

CL 325,195 45674019 Amphipod (Hyalella 

azteca)

10 D

(subchronic)

LC50 = 49 mg/kg-sed

NOAEC = 49 mg/kg-sed Supplemental

CL 325,195 45674020 Amphipod (Leptocheirus 

plumulosus)

10 D

(subchronic)

LC50 = 27 mg/kg-sed

NOAEC = 27 mg/kg-sed Acceptable

CL 322,248 45674114 Amphipod (Leptocheirus 

plumulosus)

10 D

(subchronic)

LC50 = 75 mg/kg-sed

NOAEC = 75 mg/kg-sed Acceptable

CL 322,248 45695804 Amphipod (Hyalella 

azteca)

10 D

(subchronic)

LC50 = 37 mg/kg-sed

37 mg/kg-sed Acceptable

CL 322, 250 45674108 Amphipod (Hyalella 

azteca)

10 D

(subchronic)

LC50 = 35 mg/kg-sed

NOAEC = 35 mg/kg-sed Acceptable

CL 322, 250 45674109 Amphipod (Leptocheirus 

plumulosus)

10 D

(subchronic)

LC50 = 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 anticipated to be required for antifoulant pesticides on 

one species, rice (Oryza sativa). Studies were conducted using parent tralopyril and minor 

degradate CL325,195. Results of the studies are listed in Table 27. 

Table 27 – 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 EC25 > 0.17 ppmNOAEC ≥ 0.17 ppm Acceptable

CL 325,195 45674115 Rice (Oryza sativa) 14 D EC25 > 0.17 ppm

NOAEC > 0.17 ppm

Acceptable
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 63 of 69

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 28.

Table 28 – 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 IC50 = 4.49 ppb

NOAEC = 3.1 ppb Supplemental

Econea 

technical 45674118 Marine diatom (Skeletonema costatum)

96 Hr IC50 = 2.88 ppb

NOAEC = 0.54 ppb Supplemental

Econea 

technical 45893902 Bluegreen algae (Anabaena flos-aquae)

96 hr IC50 = 350 ppb

NOAEC = 9.2 ppb Acceptable

Econea 

technical 45893903 Freshwater diatom (Navicula pelliculosa)

96 hr IC50 = 5.5 ppb

NOAEC = 0.99 ppb Acceptable

Econea 

technical 46596006

Freshwater green algae 

(Pseudokirchneriella 

subcapitata)

96 hr IC50 = 11 ppb

NOAEC = 6.8 ppb Acceptable

Econea 

technical 46619901 Marine diatom (Skeletonema costatum)

96 hr IC50 = 2.7 ppb

NOAEC = 1.5 ppb Acceptable

CL 325,195 45674116 Duckweed (Lemna gibba) 7 D IC50 = 87.2 ppb

NOAEC = 22 ppb

Acceptable

CL 325,195 45674119 Duckweed (Lemna gibba) 7 D IC50 = 13,000 ppb

NOAEC = 5,900 ppb

Acceptable

CL 325,195 45674120 Green algae (Raphidocelis 

subcapitata)

96 Hr IC50 = 440 ppb

NOAEC = 230 ppb

Supplemental

CL 325,195 45674121 Marine diatom (Skeletonema 

costatum)

96 Hr IC50 = 470 ppb

NOAEC = 280 ppb

Supplemental

CL 325,195 45893906 Freshwater diatom (Navicula 

pelliculosa)

96 hr IC50 = 1,510 ppb

NOAEC = 850 ppb Acceptable

CL 325,195 45945201 Bluegreen algae (Anabaena 

flos-aquae)

96 hr IC50 = 6,500 ppb

NOAEC = 1,400 ppb

Acceptable

CL 322,250 45674122 Duckweed (Lemna gibba) 7 D IC50 = 990 ppb

NOAEC = 530 ppb Supplemental

CL 322,250 45674123 Green algae (Raphidocelis 

subcapitata)

96 Hr IC50 = 4,620 ppb

NOAEC = 1,150 ppb Supplemental

CL 322,250 45674124 Marine diatom (Skeletonema 

costatum)

96 Hr IC50 = 1,140 ppb

NOAEC = 180 ppb Supplemental

CL 322,250 45893907 Bluegreen algae (Anabaena 

flos-aquae)

96 hr IC50 > 830 ppb

NOAEC > 830 ppb Supplemental
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 64 of 69

Chemical MRID Test Species Study 

Duration Toxicity Endpoint Classification

CL 322,250 45893908 Freshwater diatom (Navicula 

pelliculosa)

96 hr IC50 > 930 ppb

NOAEC > 930 ppb Supplemental

CL 322,250 46596014 Marine diatom (Skeletonema 

costatum)

96 hr IC50 = 660 ppb

NOAEC = 500 ppb Acceptable

CL 322,248 45674125 Duckweed (Lemna gibba) 7 d IC50 > 930 ppb

NOAEC > 930 ppb Supplemental

CL 322,248 45674126 Green algae (Raphidocelis 

subcapitata)

96 hr

IC50 > 1.99 ppm

NOAEC > 1.99 ppm Supplemental

CL 322,248 45674127 Marine diatom (Skeletonema 

costatum)

96 hr

IC50 = 1,200 ppb

NOAEC = 160 ppb

Supplemental

CL 322,248 45893904 Bluegreen algae (Anabaena 

flos-aquae)

96 hr IC50 > 1000 ppb

NOAEC = 1000 ppb Supplemental

CL 322,248 45893905 Freshwater diatom (Navicula 

pelliculosa)

96 hr IC50 > 980 ppb

NOAEC > 980 ppb Supplemental
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 65 of 69

Appendix D Comments Received 

Concerning the Preliminary Work Plan

The Agency received fourteen comments on the initial docket, described below. 

In the PWP, the Agency solicited comments on specific topics: environmental justice, water 

body impairment, trade irritants, and structure activity relationships. No comments or 

information were received during the public comment period concerning these issues.

The Office of Pesticide Programs' Antimicrobial Division (AD) has reviewed the public 

comments received on the Preliminary Work Plan (PWP) for the Tralopyril Registration Review 

Case #5114 (Docket ID Number EPA- HQ- OPP- 2013- 0217). Twelve comments were 

received from an anonymous submitter and two comments were received from the Physicians 

Committee for Responsible Medicine.

I - Anonymous Submitter Comments

The following are the comments submitted by an anonymous submitter and EPA’s responses. 

Comment 1- Section 1.5 Regulatory History 

The regulatory history is not correct. An application for registration of the technical product was 

received by the Antimicrobial Division of USEPA in May 2002. The first registration for both 

the technical and end-use product was issued on April 23, 2007. This appears to be out of cycle 

with the Registration Review timeline of 15 years. Please comment.

EPA Response to Comment 1: The Agency thanks the submitter for the information and has 

made appropriate changes to this document to reflect it.

Comment 2 - Section 2 Anticipated Data Needs 

An in vitro Salmonella typhimurium reverse mutation assay (Ames test) has already been 

reviewed by the Agency. The MRID is 43492840.

EPA Response to Comment 2: EPA concurs. This study has been reviewed and the data are 

acceptable. The FWP will be updated to remove the Ames test requirement from the Anticipated 

Data Needs in the final workplan.

Comment 3 - All of the chronic studies on mammals, anticipated to be required for Registration 

Review, which are triggered because of the freshwater uses and the need to update the drinking 

water assessment, (870.3700, .3800, .4100, 4200), are available for the precursor molecule of 

tralopyril. In the new 40 CFR 158 Data Requirements for Antimicrobial Pesticides, USEPA 

mentions its intention to use integrated approaches to testing and risk assessment, to maximize 

the use of existing data from similar compounds, including in silico predictive models. EPA 

should utilize these studies to satisfy these specific data gaps, especially considering the low 

anticipated exposure from incidental ingestion and drinking water because of the rapid 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 66 of 69

degradation half-lives by biotic and abiotic processes, hydrolysis, and photolysis. This is an 

excellent case to employ QSAR modeling and TTC analysis for tralopyril and degradates. 

EPA Response to Comment 3: The Agency encourages the use integrated approaches to testing 

and risk assessment, to maximize the use of existing data from similar compounds, including in silico 

predictive models. However, based on the list of the anticipated study requirements, once the data are 

required, the registrant will need to submit information (including any waiver requests) to fulfill the 

data requirements. The agency will review the package to decide whether the information provided 

is good enough to waive any of the required studies. The Agency and Health Canada’s Pest 

Management Regulatory Agency (PMRA) have cooperated on the development of a guidance 

document on the use of Quantitative Structure Activity Relationships [(Q)SAR] for pesticide risk 

assessors. The guidance document will be used as a base to evaluate the submitted information. The 

guidance document is located at: http://www.epa.gov/oppfead1/cb/csb_page/updates/2012/qsarguidance.html.

Comment 4 - Table 7 – Leaching from antifoulant paint in freshwater. Tralopyril hydrolyses 

rapidly, with a half-life of 0.4 days in freshwater (pH 7). Because of this property, the analytical 

method recommended by ISO 15181-6: 20121, for determining the release rate of tralopyril, 

specifies for accelerating the conversion of released tralopyril into the primary hydrolysis 

degradate CL322,250 by heat treatment and quantifying the concentration of the CL 322,250 

degradation produc, and back calculating to determine the tralopyril concentration. EPA should 

provide guidance whether ISO 15181-6: 2012 with the additional analysis of degradate CL 

322,248 would provide the Agency the information needed for risk assessment, or whether new 

sample handling procedures need to be developed and validated which stop or significantly slow 

the hydrolytic and photolytic degradation of tralopyri,l so that tralopyril and two degradates can 

all be measured.

EPA Response to Comment 4: The commenter is correct in the observation that tralopyril 

hydrolyses rapidly, with a half-life of 0.4 days in freshwater (pH 7) to form CL 322,250. The commenter 

also suggests using the analytical method recommended by ISO 15181-6 for determining the release rate 

of tralopyril. Although the commenter provides a reasonable approach for calculating the leaching rate 

and potential exposure from parent tralopyril, the ISO 15181-6 test guideline is based on simulated 

seawater, and not fresh water. As a result, the use of this methodology is not acceptable at this time. If it 

is possible to demonstrate that leaching rates are similar in fresh and sea water, then this methodology 

could possibly be used to determine the leach rates of tralopyril and its degradates.

There is a need for leaching data from treated paints in freshwater environments. Freshwater leaching 

would provide information for use in the assessment of tralopyril, and the CL 322,250 degradate in the 

environment.

Comment 5 - Section 3.1.2 Drinking Water 

Fourth bullet – EPA anticipates requesting freshwater leaching data, which are generally 

conducted according to ASTM test methods. However it is clearly stated in the standard that 

“The results of this test method do not reflect environmental biocide release rates for antifouling 

products, and are not suitable for direct use in the process of generating environmental risk 

assessments, environmental loading estimates, or for establishing release rate limits for 

regulatory purposes.” It further states that “results obtained using this test method do not reflect 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 67 of 69

actual biocide release rates that will occur in service, but provide comparisons of the release 

rate characteristics of different antifouling formulations...” and that “ the results of this generic 

rotating-cylinder test method significantly overestimate the release rate of biocide compared to 

release rates under in-service conditions.” Rather, the ISO calculation method is a much better 

predictor of leach rate under in-service use conditions. Please comment on how AD sees the 

utility of these two methods, if it is the intention to use the results from the ISO method in the 

MAMPEC modeling for risk assessments and how either release rate methods will be used to 

refine drinking water residue values.

EPA Response to Comment 5: The ASTM methods generally do not provide realistic estimates of 

the leaching that occurs from antifoulant paints in fresh and salt water. However, it is uncertain at 

this time whether or not the ISO method will be useful as an alternative to the ASTM methods 

because it is based on numerical estimations without confirmatory laboratory data. As a result, the 

EPA intends to use the ASTM leaching study results as a MAMPEC input and to address drinking 

water.

Comment 6 - Section 4.1 Environmental Fate and Exposure Pathways 

Final paragraph page 23 – EPA is critical of the leach rates used for the freshwater risk 

assessments in MRIDs 47250101 and 47301601. The leach rate for this particular AF paint 

was 1.9 μg/cm2/day based on the mass balance calculation, as prescribed by ISO 

10890:2010; the release rate used in the assessment was more than double the calculated in 

service release rate. Please also see comments under 3.1.2 for using the ISO method as a 

refinement to the leach rate determined by ASTM. 

EPA Response to Comment 6: At this time, EPA relies on ASTM methodology because of the 

availability of confirmatory laboratory data. The EPA has not received data that would validate the 

ISO calculation method, and therefore the EPA intends to use ASTM leaching rates in its risk 

assessments.

Comment 7 - Section 4.2.2 Measures of Effect (Ecotoxicology Assessment Endpoints) 

Table 12 – For terrestrial mammal/rat/acute oral, there is an acceptable study under MRID 

43492826 in which definitive LD50 values were obtained. These were reported as: 

o Males = 27.0 mg/kg 

o Females = 29.4 mg/kg 

o Combined = 28.7 (16.8 – 30.7) mg/kg (95% CI) 

EPA Response to Comment 7: EPA concurs that we can use MRID 43492824 to provide 

information for tralopyril on the LD50 for rats. Table 13 will be revised to reflect this change. 

These data were not listed in the anticipated data requirements table. Note that the comment 

refers to MRID 43492826. According to EPA’s records, MRID 43492824 was conducted with 

the parent compound and MRID 43492826 was conducted with CL 322.250. 

Comment 8 - Table 13 - For terrestrial mammal/rat/acute oral, there is an acceptable study 

under MRID 43492824 in which definitive LD50 values were obtained. These were reported as: 

o Males > 5,000 mg/kg o Females = 2,500 (1,581 – 3,954) mg/kg (95% CI) 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 68 of 69

EPA Response to Comment 8: EPA concurs that we can use MRID 43492826 to provide 

information for CL 322.250 (the defluorinated tralopyril) on the LD50 for rats. Table 13 will be 

revised to reflect this change. These data were not listed in the anticipated data requirements 

table. Note that the comment refers to MRID 43492824. According to EPA’s records, MRID 

43492824 was conducted with the parent compound and MRID 43492826 was conducted with 

CL 322.250.

Comment 9 - Table 13 - For terrestrial mammal/rat/chronic – the reference should be to Table 

7 (not table 1) for anticipated data needs. Table 7 references chronic studies for tralopyril only. 

There is no anticipated requirement for chronic studies for degradate CL 322,250. Please see 

second bullet under 2 Anticipated Data Needs suggesting the proposed use of QSAR modeling 

where appropriate. Please note that both 14-day (dose-range finding) and 28-day oral toxicity 

studies were performed with degradate CL 322,250 in September 2012 and assigned MRIDs 

48937101 and 48937102, respectively.

EPA Response to Comment 9: Please see Response to Comment 3. EPA will consider QSAR 

modeling where appropriate. The registrant should provide either the data or the QSAR rationale.

Comment 10 - Section 4.3 Exposure Analysis Plan 

See comment under 2 Anticipated Data Needs under the third bullet, with regard to the request 

for fresh water leaching data.

EPA Response to Comment 10: See response under Comment 4.

Comment 11- Appendix A Toxicology Profile 

Table 15, acute oral, rat – same comment as above under 4.2.2, Table 12.

EPA Response to Comment 11: Please see response Comment 7.

Comment 12 - Mutagenicity – see comment under 2. Anticipated Data Needs under the first 

bullet with regard to the availability of an acceptable Ames test already reviewed by the Agency.

EPA Response to Comment 12: Please see response Comment 2. The mutagenicity test will be 

removed from the anticipated data needs.

II – Physicians Committee for Responsible Medicine Comments

Comments 13 and 14 were received from the Physicians Committee for Responsible Medicine.

Comment 13 - Because the technical registrant, Janssen Pharmaceutica, Inc., is a 

pharmaceutical company we believe that data may be available, especially for the chronic and 
Docket Number EPA-HQ-OPP-2013-0217

www.regulations.gov

Page 69 of 69

reproductive toxicity endpoints. We encourage the registrant to attempt to rely on existing data 

as much as possible. Under EU regulatory authority, Tralopyril is classified as a biocide and 

was recently discussed by the Joint Research Centre, based on a publicly available agenda.

Therefore, some data may be available at the European Chemicals Agency (ECHA). We 

encourage the EPA to contact ECHA and attempt to accept any data it may receive. We also 

encourage the registrant to look into data that ECHA may hold. 

EPA Response to Comment 13: Due to the persistent degradate of the chemical tralopyril we 

believe that chronic data are necessary and anticipate requiring them. Along with Physicians 

Committee for Responsible Medicine, we encourage the registrant to submit any chronic data 

already developed, as long it satisfies the Agency’s needs to allow for a complete risk assessment 

of the chemical.

Comment 14 - If it is determined that the reproductive study is required then we suggest the 

registrant use the OECD TG 443 Extended One-Generation Reproductive Toxicity Study 

(EOGRTS) instead of the EPA guideline 870.3800 Two-Generation Reproduction. This will 

allow the registrant to conduct one extended study saving many animals lives while addressing 

endpoints of interest. The TG is currently available on the OCED web site.

EPA Response to Comment 14: EPA considers the OECD Extended One-Generation 

Reproductive Toxicity Study to be an acceptable substitute for GLN 870.3800 Two-Generation 

Reproduction.