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Tralopyril Registration Review Team 

Human Health

Timothy Dole 

Jonathan Chen 

Zoe Layton 

Environmental Fate and Effects

Zoe Layton 

Srinivas Gowda 

James Breithaupt 

Siroos Mostaghimi 

Risk Management

Wanda Henson 

Lance Wormell 

Office of General Counsel

Philip Ross 

 
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Table of Contents 

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

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

1.2 Case Overview ................................................................................................................. 7

1.3 Chemical Identification and Properties ............................................................................ 7

1.4 Use/Usage Description ..................................................................................................... 9

1.4.1 Summary of Registered Uses .................................................................................... 9

1.4.2 Usage Information .................................................................................................. 10

1.5 Regulatory History ......................................................................................................... 10

1.5.1 Recent/Pending Regulatory Actions ....................................................................... 10

1.5.2 Tolerance Information ............................................................................................ 10

1.6 Incidents ......................................................................................................................... 10

1.6.1 Human Health ......................................................................................................... 10

1.6.2 Ecological ............................................................................................................... 10

2 Anticipated Data Needs ........................................................................................................ 11

3 Human Health Risk Assessment ........................................................................................... 14

3.1 Dietary Exposure ................................................................................................................ 16

3.1.1 Food ............................................................................................................................ 16

3.1.2 Drinking Water ........................................................................................................... 16

3.2 Occupational and Residential Exposures ............................................................................ 17

3.2.1 Occupational Handler Exposure .................................................................................. 17

3.2.2 Residential Handler Exposures .................................................................................... 18

3.2.3 Residential Post-Application Exposures ...................................................................... 19

3.3 Aggregate and Cumulative Exposure ................................................................................. 19

3.3.1 Aggregate Exposures ................................................................................................... 19

3.3.2 Cumulative Exposures ................................................................................................. 20

4 Environmental Risk Assessment........................................................................................... 20

4.1 Environmental Fate and Exposure Pathways ................................................................. 21

4.2 Ecological Effects Assessment ....................................................................................... 24

4.2.1 Mode of Action ....................................................................................................... 24

4.2.2 Measures of Effect (Ecotoxicology Assessment Endpoints) .................................. 24

4.3 Exposure Analysis Plan .................................................................................................. 29

4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates ............................................ 29

5 Endocrine Disruptor Screening Program (EDSP) ................................................................. 30

6 Optional Label Changes ........................................................................................................ 30

7 Guidance for Commentors .................................................................................................... 31

7.1 Preliminary Work Plan ................................................................................................... 31

7.1.1 Trade Irritants .......................................................................................................... 31

7.1.2 Water Quality .......................................................................................................... 31

7.1.3 Environmental Justice ............................................................................................. 31

7.1.4 Structure Activity Relationships ............................................................................. 32

7.1.5 Additional Information ........................................................................................... 33

8 Next Steps ............................................................................................................................. 33

9 References ............................................................................................................................. 33

Appendix A Toxicology Profile ............................................................................................... 42
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Appendix B Environmental Fate ............................................................................................. 49

Appendix C Ecotoxicology Profile .......................................................................................... 57

List of Tables 

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

Table 2 – Anticipated Registration Review Schedule .................................................................... 6

Table 3 – Chemical Identification of Tralopyril ............................................................................. 7

Table 4 – Physical-Chemical Properties for Tralopyril ................................................................. 8

Table 5 – Chemical and Physical Properties of Tralopyril Degradates .......................................... 9

Table 6 – Summary of Tralopyril Registered Uses ...................................................................... 10

Table 7 – Studies Anticipated as Needed for the Registration Review of Tralopyril ................... 12

Table 8 –Existing Toxicological Endpoints for Dietary Exposure to Tralopyril .......................... 14

Table 9 – Existing Toxicological Endpoints for Occupational/Residential Exposure to Tralopyril

....................................................................................................................................................... 15

Table 10 – Occupational Handler Exposure Scenarios for Tralopyril .......................................... 18

Table 11 – Residential Handler Exposure Scenarios for tralopyril .............................................. 19

Table 12 – Selected Effects Endpoints for the Ecological Risk Assessment of Tralopyril .......... 25

Table 13 - Selected Effects Endpoints for the Ecological Risk Assessment of Tralopyril's Major 

Degradate CL322,250 ................................................................................................................... 26

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

Degradate CL322,248 ................................................................................................................... 28

Table 15 - Acute Toxicity Data for tralopyril ............................................................................... 42

Table 16 - Summary of parent tralopyril half-lives and degradate amounts and half-lives in 

environmental fate studies ............................................................................................................ 51

Table 17 - Sorption (Kf/Koc) of parent tralopyril and its main degradates .................................. 52

Table 18 - Physical-Chemical Properties for Tralopyril and its Primary Metabolites ................. 52

Table 19 – Reviewed and Accepted Paint Leaching Studies for Tralopyril in Seawater ............. 53

Table 20. Toxicity Profile of Tralopyril Parent and Degradates to Birds .................................... 58

Table 21. Toxicity Profile of Tralopyril Parent and Degradates to Freshwater Fish, Acute and 

Chronic .......................................................................................................................................... 59

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

Acute and Chronic ........................................................................................................................ 60

Table 23. Toxicity Profile of Tralopyril Parent and Degradates to Estuarine and Marine Fish, 

Acute and Chronic ........................................................................................................................ 61

Table 24. Toxicity Profile of Tralopyril Parent and Degradates to Estuarine and Marine 

Invertebrates, Acute and Chronic ................................................................................................. 62

Table 25. Toxicity Profile of Tralopyril Parent and Degradates to Benthic Invertebrates, 

Freshwater and Estuarine/Marine ................................................................................................. 64

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

....................................................................................................................................................... 64

Table 27. Toxicity Profile of Tralopyril Parent and Degradates to Aquatic Plants ..................... 65

List of Figures 

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

Organisms from the Antifoulant Use ............................................................................................ 24

 
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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 explains 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. 

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about tralopyril and what types of new data or 

other information would be helpful for the Agency to receive as it moves toward a decision on 

tralopyril. The Agency encourages all interested stakeholders to review the PWP and to provide 

comments and additional information that will help the Agency’s decision-making process for 

this chemical. 

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. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop and commit to a Final Work Plan (FWP) and 

anticipated schedule for the Tralopyril Case. 

Documents associated with this registration 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. 
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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 7 for more detail about 

anticipated data needs) 

Dietary (food) No N/A None None 

Dietary (drinking water) Yes 4/16/08 Updated None 

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

Inhalation Exposure 

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

Inhalation Exposure 

Aggregate Yes None New None 

Cumulative No None None None 

Tolerance Review No N/A None None 

Ecological Yes 4/24/2007 Updated 

Leaching data in fresh water 

Avian reproduction study 

Acute zebra fish study or a rainbow 

trout fish early life stage study 

Freshwater benthic invertebrate chronic 

reproduction study one with an 

amphipod and one with a chironomid for 

the parent 

Saltwater benthic invertebrate with an 

amphipod 

pKa values 

Log Kow values 

N/A = Not applicable 

Table 2 – Anticipated 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 [Year-MM-DD] 

Close Public Comment Period 2013-08 

Phase 2: Case Development 

Issue Final Work Plan 2013-12 

Issue Data Call-In (DCI) 2014-12 

Receive Data to be Considered in Risk Assessment 2017-12 

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2019-06 

Close Public Comment Period 2019-07 

Phase 3: Registration Review Decision and Implementation 

Open 60-Day Public Comment Period for Proposed Decision 2019-12 

Close Public Comment Period 2020-02 
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Issue Final Decision 2020-06 

Begin Post-Decision Followup 2020 

Total (years) 7 

*The anticipated schedule will be revised as necessary (e.g., need arising under the Endocrine Disruptor Screening Program with 

respect to the active ingredients in this case).

1.2 Case Overview 

The docket for the tralopyril Case (Case 5114) has been established at 

http://www.regulations.gov in docket number EPA-HQ-OPP-2013-0217. 

1.3 Chemical Identification and Properties 

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

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 

Common Name Tralopyril 

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: 

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. 
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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/cm3 at 20oC 

830.7370 Dissociation Constant in water pKa = 7.08 at 26C 

830.7550 Partition coefficient (noctanol/water) Log Kow 3.5 

830.7840 Solubility in water 

Water solubility by column elution at 20C: 

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

4.9) and 

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

830.7860 Solubility in Organic solvents at 20°C 

Acetone 300.5 g/L 

Ethyl acetate 236.0 g/L 

n-Heptane 7.2 g/L 

Methanol 109.1 g/L 

n-Octanol 85.2 g/L 

Xylene 5.6 g/L 

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

3.45 x 10-10 mm Hg at 25C 
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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) 3.722 4.172 1.682

Solubility in water mg/l 5.63 17.95 476 

Vapor pressure mm Hg at 

25C 7.62 x 10-7 3.45 x 10-9 7.0 x 10-11

Henry’s Law (m3mol-1) 5 x 10-8 7.65 x 10-11 4.8 x 10-14

References: EPI Suite 4.1; 

1 Values used in Henry’s Law Calculations 

2 These EPI-Suite 4.1 values for Log P are questionable because the experimental log P value for parent traloyril 

with 3 fluorines and 1 bromine was 3.5 (MRID 45673906). The loss of halogens results in compounds that are 

more water soluble and therefore the log P is expected to be lower because of preferential partitioning into the 

water phase. 

1.4 Use/Usage Description 

1.4.1 Summary of Registered Uses 

A listing of the registered uses of tralopyril is included in Table 6. Tralopyril is registered for 

use as antifoulant in paint for both recreational and 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 six 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 

C

N

Cl

N OH

HO
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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 or brush/roller. 

Table 6 – Summary of Tralopyril Registered Uses 

Use Application Method Amount Ai in Paint Paint Coverage 

Boats, ships, hull bottom Brush, Roller, Airless Sprayer 2.9 to 7.28 percent 267 to 528 ft2/gallon 

1.4.2 Usage Information 

According to the Section Seven Tracking System (SSTS) database, the production volume for 

tralopyril is less than 20,000 kg per year for the years 2008 to 2011. 

1.5 Regulatory History 

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

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

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

product containing tralopyril was registered in 2007. There are currently 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. 

1.5.1 Recent/Pending Regulatory Actions 

There are currently products awaiting registration decisions, these products are not anticipated to 

affect this work plan. 

1.5.2 Tolerance Information 

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

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

1.6 Incidents 

1.6.1 Human Health 

The Incident Data System (IDS) of The Office of Pesticide Programs (OPP) of Environmental 

Protection Agency (EPA) contains reports of incidents from various sources, including 

registrants, other federal and 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. 

1.6.2 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. 
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2 Anticipated Data Needs 

Table 7 presents a summary of the data anticipated as being needed to support this registration 

review. 
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Table 7 – 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 Expo

Studies Anticipated to be Required through the Registration Review DCI 875.1200 887.1400 

Outdoor Exposure, Dermal Outdoor Exposure, Inhalation tralopyril 36 Occupational Handler Residential Handler Antifoulant Paint 

Airless Spray AppPainters Brush/Roller AppPainters 

870.3700 Developmental Toxicity (non-rodent species) tralopyril 24 Drinking Water Antifoulant Paint (Fresh Water Uses) Oral exposures to 

contaminated with degradates. 

870.3800 Reproductive Toxicity 

tralopyril 

24 

Drinking Water Antifoulant Paint 

(Fresh Water Uses) 

Oral exposures to contaminated with degradates. 

870.4100 Chronic Oral Toxicity 

tralopyril 

36 

Drinking Water Antifoulant Paint 

(Fresh Water Uses) 

Oral exposures to contaminated with degradates. 

870.4200 Cancer Study 

tralopyril 

36 

Drinking Water Antifoulant Paint 

(Fresh Water Uses) 

Oral exposures to contaminated with degradates. 

870.5100 

In vitro Salmonella 

typhimurium Reverse Mutation Assay 

tralopyril 

12 

Drinking Water Antifoulant Paint 

(Fresh Water Uses) 

Oral exposures to contaminated with degradates. 

850.1075 or 850.1400 

Acute (zebra fish) or Earlylife Stage (rainbow trout) tralopyril 24 Ecological Antifoulant paint (Fresh water Uses) Exposure of aquat

or its degradates i

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 aquator its degradates i

Special Study2

Whole sediment, chronic marine invertebrate (1 species-amphipod) 

CL 322,250 24 Ecological Antifoulant paint (Salt water uses) Exposure of saltw

its degradates in s

850.2300 Avian Reproduction tralopryil 24 Ecological Antifoulant paint (Fresh water uses) Exposure of aquat

or its degradates i
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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 Expo

Special Study3

Leaching from antifoulant paint in freshwater 

EP (monitor tralopyril and degradates) 12 

Ecological Antifoulant Paint 

(Fresh Water Uses) 

Oral exposures to contaminated with degradates. Exposure of aquator its degradates i

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 aquatdegradates in surf

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 employ

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

The loss of halogens to form the degradates results in compounds that are more water soluble than the parent compound, and therefore arlower log P value than the parent compound.
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3 Human Health Risk Assessment 

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

review. Tables 7 and 8 presents the endpoints used in EPA’s most recent human health risk 

assessments. 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/m3 based 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/m3

 using the formula HEC= 

LOAEL * 6 hours/8 hours * RDDR where the RDDR = 1.57. It also estimated that the 

level of concern for the uncertainty 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/m3

 by the uncertainty factor of 

100 yields an “RfC” of 0.24 mg/m3

 as an eight hour TWA. This Rfc value would most 

likely be used to assess inhalation exposures for occupational handlers. 

 Dermal exposures were assessed in the 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. 

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

Exposure 

Scenario 

Dose Used 

for 

Endpoint 

Uncertainty Factors for Risk 

Assessment 

Study and Toxicological 

Effects 

Acute 

Dietary 

6.3 mg/kg/day 

(LOAEL, 

Females) 

10X intraspecies, 

10X intraspecies, 

3X conversion of the LOAEL to a NOAEL 

Acute RfD = 6.3 mg/kg/day 

 10 x 10 x 3 

 

 = 0.021 mg/kg/day 

Subchronic (90) Day Oral 

LOAEL = 6.3 mg/kg/day (LDT) 

for females based on 

microscopic findings of the brain 

and spinal cord. 

NOAEL could not be determined 

in the females. 

LOAEL = 16.2 mg/kg/day in 

males. NOAEL = 5.2 mg/kg/day 
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Exposure 

Scenario 

Dose Used 

for 

Endpoint 

Uncertainty Factors for Risk 

Assessment 

Study and Toxicological 

Effects 

Chronic 

Dietary 

(general 

population)

6.3 mg/kg/day

(LOAEL, 

Females) 

10X intraspecies, 

10X intraspecies, 

3X conversion of the LOAEL to a NOAEL 

10X data base uncertainty (missing chronic 

study and a neurotoxicity study) 

 

Chronic RfD = 6.3 mg/kg/day 

 10 x 10 x 10 x 3 

 

 = 0.0021 mg/kg/day 

Subchronic (90) Day Oral 

LOAEL = 6.3 mg/kg/day (LDT) 

for females based on 

microscopic findings of the brain 

and spinal cord. 

NOAEL could not be determined 

in the females. 

LOAEL = 16.2 mg/kg/day in 

males. NOAEL = 5.2 mg/kg/day 

Table 9 – Existing Toxicological Endpoints for Occupational/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/m3

 based 

chronic and subacute 

inflammation, ulcerations, 

exudates, epithelial hyperplasia, 

hyperkeratosis and degeneration of the olfactory 

epithelium in the nasal section 

N1 to N3. 

Decreased body weight gain 

was also seen at this dose level. 

Inhalation

Long-Term 

(6 months – lifetime)

Risk assessment not required based for this use pattern 

Cancer No cancer data available 

*Note - The toxicological 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. 
Docket Number EPA-HQ-OPP-2013-217 

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3.1 Dietary Exposure 

3.1.1 Food 

There are no food uses for tralopyril and therefore the EPA does not anticipate the need to 

conduct a dietary (food) risk assessment. 

3.1.2 Drinking Water 

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

memorandum dated April 16, 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 

the 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. Deparent 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 available2,3 that 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 MAMPEC (3.0)5 is currently available. The most recent version 

will be used to estimate refined drinking water residue values. 

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

a freshwater lake scenario in MAMPEC. The 2008 memo states that the drinking 

water residue estimate used as an input into DEEM-FCIDTM was determined using 

Version 1.6 of the Marine Antifoulant Model to Predict Environmental Concentrations 

(MAMPEC) for the primary degradation products of tralopyril, CL 322,250 and CL 

322,248. MAMPEC is an integrated hydrodynamic and chemical fate models 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 refining a fresh water lake 

 

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 
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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 MAMPEC, the Agency expects to refine the MAMPEC model estimations 

using freshwater leaching data. It has been determined that in order to properly address 

the potential freshwater risk, leaching data in fresh water are 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. 

3.2 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 are no longer valid. These assessments will need to be 

reassessed using the updated values. 

3.2.1 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 a 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 

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. 

 

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. 
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Page 18 of 66

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 9 will need to be reassessed during 

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

 The product assessed at the time of 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/m3 per lb ai handled when expressed 

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

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

 The amount of paint handled was assumed in the occupational exposure assessment7 to be 

either 14 gallonsbased 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 10 – Occupational Handler Exposure Scenarios for Tralopyril 

Scenario Exposure Route(s) Duration

Airless Sprayer Application of Antifoulant Paint Inhalation Short, Intermediate, and Long Term 

3.2.2 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 

 

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.
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Page 19 of 66

based a product (2693-220, Trilux White Antifouling Paint) that contains 3.9 percent tralopyril. 

The dermal exposures were assessed using PHED unit exposure data for the brush/ roller 

scenario and the inhalation exposures were assessed using data from a literature study9. The 

amount of paint handled was based on the hull sizes of 14, 20 and 30 feet, a coverage of 400 ft2

per 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 11 – Residential Handler Exposure Scenarios for tralopyril 

Scenario Exposure Route(s) Duration

Applying Paint Using Brushes and Rollers Dermal Short Term 

3.2.3 Residential Post-Application Exposures 

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

not anticipated. 

3.3 Aggregate and Cumulative Exposure 

3.3.1 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 

 

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)
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Page 20 of 66

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. 

3.3.2 Cumulative Exposures 

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

cumulative risk approach based on a common 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) 

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

To fill toxicity data gaps remaining for tralopyril’s major degradates CL322,250 and CL322,248, 

they will be assumed to be as toxic as the parent compound. 

 

10 U.S. EPA (2007). An AD Memo from Richard Petrie to Marshall Swindell entitled EconeaTM (tralopyril) 

Antifoulant New Chemical Registration, Ecological Hazard Assessment and Environmental Risk Characterization 

(PC Code: 119093). 
Docket Number EPA-HQ-OPP-2013-217 

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Page 21 of 66

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 

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 

 

11 MRIDs 45673908, 45673909, 45673910, 45673911, 45673912 
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anaerobic conditions (representing bottom sediment) and in saltwater conditions and did not 

degrade12. The study results may be seen in Table 16. 

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 

18). 

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 

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

fields. 

 

12 MRID 45673910 

13 MRIDs 45673913, 45673914 

14 MRID 45673910 contained the maximum formation (7.1 % of applied tralopyril) of all environmental fate studies. 

Degradates formed at <10 % of applied parent compound are considered to be “minor” (5/10/11 memorandum from 

Don Brady, Environmental Fate and Effects Division, Guidance for Determining Pesticide Residues of Concern in 

Drinking Water in Coordination with the HED ROCKS ) 
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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 19) 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. 
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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 12, Table 13, and Table 14 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 12, Table 13, and Table 14. 

A more detailed description of the ecotoxicity studies are provided in Appendix C .

Stressor

Source

Receptors

and Exposure

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to

habitat

Surface Water/Sediment

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills

or integument

Aquatic Plants

Non‐vascular

Vascular

Uptake or sorption/cell, roots,

leaves,

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

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

Ingestion

Domestic Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway

contributing to risk

Low likelihood of

contributing to risk

In‐Service Use of  Tralopyril in Boat Paints as an Antifoulant

WWTP

microorganisms

Uptake or

sorption

Population

Respiration

inhibition

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

Paint Leaching and Removal in Water
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Table 12 – 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 
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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 

LC50 = Not 

established—

Will use 90-d 

or similar 

results for 

assessing risk2

Acceptable See 

Table 15

MRID 

45673915 

Chronic N/A Not Required 

1 Rainbow trout was the most acutely sensitive species tested. Because there can be wide differences in species 

sensitivity a chronic value is needed for this species so that chronic risk is not underestimated. This anticipated data 

requirement may be met by either a 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 13 - 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 
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Receptor Group Surrogate Species Risk 

Scenario 

Study 

Duration 

Toxicity 

Endpoint 

Classification/ 

Comments Reference 

Chronic 34-Day NOAEC = 240

ppb Acceptable MRID 

45674106 

Aquatic Animals: 

Marine/Estuarine 

Invertebrates 

Mysid 

(Americamysis 

bahia) 

Acute 96-Hour 

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 Data Anticipated to Be Required (See Table 1) 

Chronic Data Anticipated to Be Required (See Table 1) 

1 No fish early life stage (ELS) test with the most acutely sensitive tested species, rainbow trout, is available. A 

chronic value for the rainbow trout is anticipated to be required. The anticipated data requirement may be met in a 

number of ways such as submittal of a rainbow trout ELS 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. 
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Table 14 - 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.
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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 

MAMPEC runs from the Barbours Point (Houston) were used for ecological risk assessment of 
Docket Number EPA-HQ-OPP-2013-217 

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Page 30 of 66

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

fresh water lake scenario for use of 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. Tralopyril is not among 

the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. 

Accordingly, as part of registration review, EPA will issue future EDSP orders/data call-ins, 

requiring the submission of EDSP screening assays for tralopyril. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

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

website: http://www.epa.gov/endo/. 

6 Optional Label Changes 
Docket Number EPA-HQ-OPP-2013-217 

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Page 31 of 66

It is recommended that the labels be revised to indicate that full face respirators with organic 

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

7 Guidance for Commenters 

7.1 Preliminary Work Plan 

The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the tralopyril registration review case. 

7.1.1 Trade Irritants 

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency 

will work to harmonize tolerances and international maximum residue limits (MRLs) and may 

modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any trade 

irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in 

key export markets, providing as much specificity as possible regarding the nature of the 

concern. 

7.1.2 Water Quality 

Neither parent tralopyril nor its degradates are identified as a cause of impairment for pesticidal 

uses in any water bodies listed as impaired under section 303(d) of the Clean Water Act20. All 

sites listed for pesticides, and organics were reviewed and none of them listed tralopyril, CL 

322,250, or debrominated CL 322,250 (CL 322,248). 

More information on impaired water bodies and TMDLs21 can be found at EPA’s website22. The 

Agency invites submission of water quality data for this pesticide. To the extent possible, data 

should conform to the quality standards in Appendix A of the OPP Standard Operating 

Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s 

Registration Review Risk Assessment and Management Process23 in order to ensure they can be 

used quantitatively or qualitatively in pesticide risk assessments. 

7.1.3 Environmental Justice 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

 

20 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885 

21 TotalMaximum Daily Load (TMDL). TMDL is a calculation of the maximum amount of a pollutant that a 

waterbody can receive and still safely meet water quality standards 

(http://water.epa.gov/lawsregs/lawsguidance/cwa/tmdl/index.cfm ) 

22 http://water.epa.gov/lawsregs/lawsguidance/cwa/tmdl/index.cfm 23 http://www.epa.gov/oppsrrd1/registration_review/reg_review_process.htm 
Docket Number EPA-HQ-OPP-2013-217 

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Page 32 of 66

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to tralopyril compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population. 

7.1.4 Structure Activity Relationships 

EPA must rely upon information of appropriate quality and reliability for each decision made by 

the Agency. In the Office of Pesticide Programs (OPP), the evaluation process for a pesticide 

chemical traditionally begins with the applicant’s submission of a set of studies conducted with 

the specific pesticide chemical of interest. The use of the results of such testing (measured data) 

is a logical, scientifically rigorous process that identifies the physical, chemical, and 

environmental fate properties of the pesticide, as well as the dose and endpoints at which an 

adverse effect can occur in various animal species. 

Today, there is significant interest in alternative techniques, i.e., techniques other than data 

generation that could significantly inform the Agency’s decision-making process. Recently, OPP 

has made increasing use of structure activity relationship (SAR) as part of its regulatory 

decision-making process. In the SAR process, a chemical's molecular structure is compared to 

that of other chemicals for which data are available. These structural similarities are then used to 

make predictive judgments about a chemical’s physical, chemical, and biological properties. 

Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly 

related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To 

develop a QSAR, a selected set of measured data on a single physical, chemical, or biological 

property is used to derive a model (an equation) to predict the value of that property. 

Since SAR assessments and QSAR modeling are another set of tools that are available to Agency 

scientists, OPP has begun a process shift that envisions shifting from the current study-by-study 

approach to an approach in which the use of predicted data, generated using validated models, is 

considered along with information from open literature and studies specifically generated under 

Part 161 requirements. All relevant information would be considered as part of a weight-of-theevidence evaluation. 

At this time, EPA believes that for certain endpoints, especially physical/chemical and fate 

properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements 

for many antimicrobial pesticide chemicals. When considering biological properties, at this time, 

EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of 

chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is 

appropriate because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a 

screening-level assessment procedure rather than multiple tiers of assessments with progressively 

more data requirements. 

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the 

tralopyril case, then the Agency invites submission of this information. The submitter would be 

expected to supply a rationale describing the utility of the information and provide 

documentation on the scientific validity of the information. The determination that the predicted 
Docket Number EPA-HQ-OPP-2013-217 

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Page 33 of 66

data fulfills the data requirement would be at the sole discretion of the Agency. Pre-submission 

consultation with the Agency is encouraged. 

7.1.5 Additional Information 

Stakeholders are also specifically asked to provide available information and data that will assist 

the Agency in refining its risk assessments, including any species-specific ecological effects 

determinations. The Agency is interested in receiving the following information: 

1. Confirmation on the following label information: 

A. Sites of application 

B. Formulations 

C. Application methods and equipment 

D. Maximum application rates 

E. Frequency of application, application intervals and maximum number of 

applications 

F. Geographic limitations on use 

2. Use or potential use distribution 

3. Use history 

4. Usage/use information for non-agricultural uses (e.g., materials preservation) 

5. Typical application interval 

6. State or local use restrictions 

7. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency 

8. Monitoring data 

8 Next Steps 

After the 60-day comment period closes in August 2013, the Agency will review and respond to 

any comments received in a timely manner, and then issue a Final Work Plan for the tralopyril 

case. 

9 References 

Best, S.; McGuire, G. (1999) Identification of Unknown Component 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 
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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 

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 
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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 

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 
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Page 36 of 66

Knox III, D. (2011) Econea Technical: Preliminary Analysis. Project Number: 32442, 

AGR/4539, P809. Unpublished study prepared by Eurofins/Product Safety Laboratories. 

84p. 48596802 

Koga, Y. (2011) Bioconcentration Study of 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 

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 
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Page 37 of 66

Millen, W. (2001) Validation of HRGC Method M-3467.01 to Assay for CL 312264 and CL 

322,697 in the Technical Grade of AC 303268: Lab Project Number: APBR 1153: 00-

APBR-1125-9. Unpublished study prepared by BASF. 53 p. {OPPTS 830.1700}. MRID 

45673903 

Milligan, F.; Williams, S.; McGuire, G. (1997) Supplement to Hydrolytic Stability Report NO 

15348: Identification of Hydrolytic Degradation Products of (Carbon-14)-R107894: Lab 

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

Research. 37 p. 45673909 

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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 
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Page 38 of 66

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 

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Sinning, D. (2002) Leach Rate Determination of Sigma Nexxium 20 Paint Containing Sea Nine 

211 and AFO28 Antifoulings: Lab Project Number: 630-16. Unpublished study prepared 

by Case Consulting Laboratories, Inc. 34 p. 45673201 

Sinning, D. (2008) Release Rate Determination of Tralopyril from Smart Solution. Project 

Number: 3990/01. Unpublished study prepared by Case Consulting Laboratories, Inc. 27 

p. 47500201 

Sinning, D. (2011) Leach Rate Determination of Pettit Hydrocoat ECO Antifouling Pain 1104 

White: Final Report. Project Number: 390/100. Unpublished study prepared by Case 

Consulting Laboratories, Inc. 34p. 48734904 

Sinning, D. (2011) Leach Rate Determination of Pettit Hydrocoat 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 
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Page 39 of 66

Teixeira, D. (2001) R107894--Determination of Effects on Seedling Emergence of Rice (Oryza 

sativa): Lab Project Number: 13751.6127: AGR 362. Unpublished study prepared by 

Springborn Laboratories, 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 

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 

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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 

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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 

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

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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 

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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 
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Page 41 of 66

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. 
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Appendix A Toxicology Profile 

Acute Toxicity for Product Labeling 

As summarized in Table 1, 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 15 - 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 
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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. 
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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. 
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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/m3 for 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/m3

 Phase II neurotoxicity study group were found dead on study Days 0, 20, and 

85, respectively. Additionally, an 80 mg/m3

 female in the Phase II neurotoxicity study group 

was found dead on Day 0 after the first exposure. Since there were numerous deaths in the 80 

mg/m3

 group 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/m3 test 

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. 
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In the Phase I of the study, the LOAEL was 20 mg/m3

 for male and female is 20 mg/m3 based 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/m3 groups 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/m3

 animals 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/m3

 in males based on decreased motor activity and 80 

mg/m3

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

neurotoxicity NOAEL was 20 mg/m3 for 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 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). 
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Page 47 of 66

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-2013-217 

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Page 48 of 66

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). 

 
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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 hydrolysis24 and photodegradation 

in water,25 and by biotic processes26 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 16). 

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) values27. 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 results28 , neither parent tralopyril nor its 

degradates are expected to volatilize from water (Table 18). 

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-

 

24 MRIDs 45673908, 45673909 

25 MRID 47128801 

26 Aquatic metabolism, MRIDs 45673910, 45673911, 45673912 

27 The Log P values in Table 18 for the degradates are questionable because the EPI-Suite 4.1 model predicts higher 

water solubility than parent compound. The 830.7550 test (log P) involves shaking a pesticide in a mixture of 

octanol and water and more water soluble compounds will tend to partition to water, lowering the predicted log P. 28 MRIDs 45673910, 45673911, 45673912, EPI-Suite 4.1 
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97 %, respectively. For CL 322,250, the sorption for the freshwater and saltwater sediments was 

96-98 and 57-95 %, respectively29 . However, the total sorption to sediment in the aquatic 

metabolism studies30 did not exceed 70 %. In the anaerobic aquatic metabolism study31, 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,32 the total sorption 

(extractable plus unextractable residues) was 42 and 21 % for the freshwater and salt water 

systems, respectively. 

The apparent difference in sorption can be 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 studies33, 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 studies34 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 

sediment35. 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-term36. Also, the degradation 

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

halogen molecules (fluorine, bromine)37. As a result, further degradation of the parent 

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

sorption (Table 17 and Table 18). 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 17). In the aquatic metabolism studies38, 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 19). 

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

bioconcentration in fish study39 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. 

 

29 MRIDs 45673913, 45673914, Table 16 

30 MRIDs 45673910, 45673911, 45673912 

31 MRID 45673910 

32 MRIDs 45673911, 45673912 

33 MRIDs 456734913, 45673914 

34 MRIDs 45673910, 45673911, 45673912 

35 835.1230 test guideline, http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0006 36 OCSPP 835.4300 and 835.4400 

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

38 MRIDs 45673910, 45673911, 45673912 

39 OCSPP 850.1730, MRID 48680501 
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Table 16 - 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 o

C- Linear half-lives of 14, 

0.4, 0.1, and 0.1 days in pH 5, 7, 

and 9 water fresh and seawater 

(pH 8), respectively 

Distilled water

9.4-96.2 % 

(30 d)1,2 

(no half-life 

calculated-- 

stable)6

1.4-4.6 % (30 d)1

Minor 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 d 25 % (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 d 36-47 % 

(21-30 d)1,2 

(half-life of 23 

days)

1.9% (30 d)1 30.3 % (30 d)1,2

1

 End of study period. 

2

 Numbers in red indicate significant percentages of applied compound. 

3

 CL 322,250 is parent tralopyril minus three fluorine molecules 

4

 CL 325,195 is debrominated parent tralopyril 
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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 

7

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

Table 17 - 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 18 - 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 o

C 

1.42 x 10-10 at 

20C1

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 10-7 5 x 10-8 EPI-Suite 4.1

CL 325,195 302.64 17.95 4.172 None 3.45 x 10-9 7.65 x 10-11 EPI-Suite 4.1

CL 322,248 

(Debrominated 

CL 322,250) 

248.67 476 1.682

 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.
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Table 19 – Reviewed and Accepted Paint Leaching Studies for Tralopyril in Seawater 

MRID 

Paint 

Ingredients (% 

w/w) 

Temp 

(

o

C) 

CL 

322,25040

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

 

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

analysis. 
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MRID 

Paint 

Ingredients (% 

w/w) 

Temp 

(

o

C) 

CL 

322,25040

measured? 

Review 

Date 

Results 

Maximum, Minimum, and Average Units are 

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

45673201 Sigma Nexxium 20 

Paint (Red-Brown) 

Tralopyril, 3.68% 

RH-5287, 3.43% 

25 Yes 1/6/05 Rate Value Time Interval 

Maximum 20.8 3 days 

Minimum 6.0 14 days 

Average 13.3 1-14 days 

Average 10.6 14-45 days 

Cumulative 188 1-14 days 

Cumulative 454 14-45 days 

46934508 International 

Copper-Free Paint 

Tralopyril, 3.9 % 

RH-5287, 4.12 % 

25 Yes 1/11/07 Rate Value Time Interval 

Maximum 7.0 31 days 

Minimum 4.15 77 days 

Average 5.9 1-14 days 

Average 5.8 1-91 days 

Cumulative 82.2 1-14 days 

Cumulative 512 1-91 days 

47238912 HMF Antifouling 

Paint I 

Tralopyril, 7.28% 

Zn pyrithione,6.38% 

 Yes 1/10/08 Rate Value Time Interval 

Maximum 13.5 31 days 

Minimum 6.8 77 days 

Average 9.2 1-14 days 

Average 10.3 1-91 days 

Cumulative 127 1-14 days 

Cumulative 912 1-91 days 

47550801 Lag 2007 025, Black 

Paint 

Tralopyril, 3.9% 

Zn pyrithione, 

4.12% 

25 Yes 1/8/09 Rate Value Time Interval 

Maximum 17.9 14 days 

Minimum 6.7 1 day 

Average 13.7 1-14 days 

Average 14.6 1-45 days 

Cumulative 194 1-14 days 

Cumulative 678 1-45 days 

47550801 Lag 2007 025, Red 

Paint 

Tralopyril, 3.9 % 

Zn pyrithione, 

4.12% 

25 Yes 1/8/09 Rate Value Time Interval 

Maximum 19 7 days 

Minimum 5.4 1 day 

Average 14.2 1-14 days 

Average 15.9 1-45 days 

Cumulative 206 1-14 days 

Cumulative 751 1-45 days 

47550801 Lag 2007 025, Blue 

Paint 

Tralopyril, 3.9% 

Zn pyrithione , 4.12 

% 

25 Yes 1/8/09 Rate Value Time Interval 

Maximum 18.4 14 days 

Minimum 5.7 1 day 

Average 13.3 1-14 days 

Average 14.4 1-45 days 

Cumulative 186 1-14 days 

Cumulative 670 14-45 days 
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MRID 

Paint 

Ingredients (% 

w/w) 

Temp 

(

o

C) 

CL 

322,25040

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 
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MRID 

Paint 

Ingredients (% 

w/w) 

Temp 

(

o

C) 

CL 

322,25040

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 

490460031 Armor SolventBased Antifouling 

Paint 

Tralopyril, 5.6 % 

Zn pyrithione, 4 % 

25 Yes N/A Rate Value Time Interval 

Maximum 34.5 3 days 

Minimum 12.9 45 day 

Average 28.6 1-14 days 

Average 22.0 1-45 days 

Cumulative 390 1-14 days 

Cumulative 986 1-45 days 1

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

 
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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 20. These results indicate that tralopryil 

technical is moderately to highly toxic to avian species on an acute oral basis. All avian acute 

oral data requirements are fulfilled for the parent. 

Avian acute oral testing was also conducted on the CL325,195 metabolite of tralopryil. The 

results of testing are provided in Table 20. These results indicate that the CL325,195 degradate 

is slightly toxic to practically non-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 20. 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. 
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Table 20. 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 15. 

Toxicity to Freshwater Aquatic Receptors 

Freshwater Fish, Acute—Parent and Degradates

Two freshwater fish, one warm water species and one cold water species, toxicity studies using 

the technical grade of the active ingredient (TGAI) are anticipated to be required to establish the 

toxicity of tralopyril to fish. This information is used to determine label hazard statements, as 

well as to estimate risk to freshwater fish from the proposed use. The preferred test species are 

rainbow trout (a coldwater fish) and bluegill sunfish (a warmwater fish). Results for the parent, 

tralopyril, are tabulated in Table 21. These results indicate that tralopryil is very highly toxic to 

freshwater fish on an acute basis. All acute freshwater fish data requirements have been fulfilled 

for the parent. 
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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 21; 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 21. 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 
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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 

22. 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 22. The results indicate that CL322,250 is moderately to highly toxic to 

aquatic invertebrates on an acute basis and that CL322,248 is slightly toxic to aquatic 

invertebrates on an acute basis. Results 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 22. 

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 22 – 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 
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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 23. 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 23 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 23. 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 
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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 ppba

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 ppba

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 24. 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 24. 

Table 24. 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 
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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 25. 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. 
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Table 25. Toxicity Profile of Tralopyril Parent and Degradates to Benthic Invertebrates, 

Freshwater and Estuarine/Marine 

Chemical MRID Test Species Study 

Duration Toxicity Endpoint Classification

Econea 

technical 45674010 Amphipod (Hyalella 

azteca) 

10D 

(subchronic)

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/kgsed Acceptable 

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 26. 

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

Plants 

Chemical MRID Test Species Study 

Duration Toxicity Endpoint Classification 

Econea 

technical 45674115 Rice (Oryza sativa) 14 D EC25 > 0.17 ppm NOAEC ≥ 0.17 ppm Acceptable 

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

NOAEC > 0.17 ppm Acceptable 
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Aquatic Plants—Parent and Degradates

Aquatic plant testing is required for antifoulant pesticides such as tralopyril. Testing is required 

on one vascular plant (Lemna sp.), and four species of algae. Results of submitted studies for 

tralopryil and major degradates are summarized in Table 27. 

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

Chemical MRID Test Species Study 

Duration Toxicity Endpoint Classification

Econea 

technical 45674117 Freshwater green algae (Raphidocelis subcapitata) 96 Hr 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 
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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 

.