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Alkyl Trimethylenediamines Registration Review Team

Human Health & Environmental Effects

Patricia Jennings

James Breithaupt

Bill Erickson 

Sumitra Biswas

Katelynn King

Timothy Dole

Timothy McMahon

Risk Management

Donna Kamarei 

Zebora Johnson 

Rose Kyprianou 

Office of General Counsel

Philip Ross 
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TERMS, ABBREVIATIONS AND SYMBOLS

A.I. or a.i. active ingredient

ASRI activated sludge respiration inhibition

BCF bioconcentration factor 

°C degrees Celsius

CAS Chemical Abstracts Service 

CFR Code of Federal Regulations 

DCI data call-in

EC50 median (or 50 percent) effect concentration

ECOTOX ECOTOXicology

EDSP Endocrine Disruptor Screening Program 

E-FAST Exposure and Fate Assessment Screening Tool

EPA Environmental Protection Agency 

FDA Food and Drug Administration 

FFDCA Federal Food, Drug, and Cosmetic Act

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

FQPA Food Quality Protection Act 

FWP Final Work Plan

g/mol grams per mole

GLN guideline number

HPV high production volume

IDS Incident Data System 

Koc organic carbon normalized soil-water partition coefficient

Kow octanol-water partition coefficient

LC50 median (or 50 percent) lethal concentration

LD50 median (or 50 percent) lethal dose

LOAEC lowest-observed-adverse-effect-concentration 

LOAEL lowest-observed-adverse-effect-level

Log Kow logarithm of the octanol-water partition coefficient

μg microgram

ml/g milliliter per gram

mg/kg milligram per kilogram

mg/kg/day milligram per kilogram per day 

mg/L milligram per liter

mm Hg millimeter of mercury

MOE margin of exposure 

MRID Master Record Identification Number

MRL maximum residue limit 

N/A not applicable 

nm nanometers

NOAEC no-observed-adverse-effect-concentration

NOAEL no-observed-adverse-effect-level

OCSPP Office of Chemical Safety and Pollution Prevention

OECD Organization for Economic Co-operation and Development

OPP Office of Pesticide Programs

PC Code Pesticide Chemical Code

pH power of hydrogen or power of the concentration of the hydrogen ion

pKa power of the acid dissociation constant or negative base-10 logarithm of the acid 

dissociation constant of a solution

ppb parts per billion 
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ppm parts per million

PWP Preliminary Work Plan

QSAR quantitative structure-activity relationship

RED Reregistration Eligibility Decision

SAR structure activity relationship

SF safety factor

TGAI technical grade active ingredient

TMDL total maximum daily loads

TOR Threshold of Regulation 

UF uncertainty factor

UV/VIS ultraviolet/visible light absorption

WWTPs wastewater treatment plants
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Table of Contents

1 Introduction .............................................................................................................................7

1.1 Statutory and Regulatory Authority .................................................................................7

1.2 Updates to the Work plan .................................................................................................7

1.3 Case Overview..................................................................................................................8

1.4 Chemical Identification and Properties ..........................................................................10

1.5 Use/Usage Description ...................................................................................................11

1.5.1 Registrations............................................................................................................11

1.5.2 Summary of Registered Uses..................................................................................11

1.5.3 Usage Information...................................................................................................12

1.6 Regulatory History .........................................................................................................12

1.6.1 Tolerance Information.............................................................................................12

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

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

1.7.2 Ecological................................................................................................................13

2 Anticipated Data Needs.........................................................................................................13

3 Human Health Risk Assessment ...........................................................................................17

3.1 Toxicological Endpoints.................................................................................................17

3.2 Dietary Exposure ............................................................................................................18

3.2.1 Food.........................................................................................................................18

3.2.2 Drinking Water........................................................................................................18

3.3 Occupational and Residential Exposures .......................................................................19

3.3.1 Occupational Exposures..........................................................................................19

3.3.2 Residential Exposures.............................................................................................19

3.4 Aggregate and Cumulative Exposure .............................................................................19

3.4.1 Aggregate Exposures...............................................................................................19

3.4.2 Cumulative Exposures.............................................................................................20

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

4.1 Environmental Fate Assessment.....................................................................................20

4.1.1 Water Quality ..........................................................................................................21

4.2 Environmental Exposure Pathways................................................................................21

4.3 Ecological Effects Assessment.......................................................................................22

4.3.1 Mechanism of Action ..............................................................................................22

4.3.2 Available Endpoints from Submitted Studies.........................................................22

4.3.3 Open Literature .......................................................................................................23

4.4 Exposure Analysis Plan ..................................................................................................23

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates.............................................23

4.4.2 Screening Level Down-the-Drain Analysis ............................................................23

5 Endocrine Disruptor Screening Program (EDSP).................................................................24

6 Optional Label Changes........................................................................................................25

7 Next Steps .............................................................................................................................25

8 References.............................................................................................................................26

Appendix A Toxicology Profile ...............................................................................................28

Appendix B Environmental Fate..............................................................................................38

Appendix C Ecotoxicology Profile ..........................................................................................44

Appendix D Chemical and Physical Properties of ATMD Compounds..................................53
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Appendix E Comments Received Concerning the Preliminary Work Plan ............................58

List of Tables

Table 1 – Anticipated Risk Assessments for Registration Review................................................... 8

Table 2 – Anticipated Registration Review Schedule....................................................................... 9

Table 3 – Chemical Identification and Product Chemistry of ATMD Chemicals.......................... 10

Table 4 – ATMD Registered Products by PC Code and Type........................................................ 11

Table 5 – ATMD Registered Uses.................................................................................................. 11

Table 6 – Anticipated Data Needs for the Registration Review of ATMD Chemicals .................. 15

Table 7 – Toxicological Endpoints for ATMD............................................................................... 18

Table 8 – Available Ecological Effects Endpoints.......................................................................... 22
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1 Introduction

This document is the United States Environmental Protection Agency’s (USEPA, EPA or “the 

agency”) Final Work Plan (FWP) for alkyl trimethylenediamines, herein referred to as ATMD. 

The FWP document explains what EPA's Office of Pesticide Programs (OPP) knows about

ATMD, 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 ATMD’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 ATMD and what types of new data or other 

information would be helpful for the agency to receive as it moves toward a decision on ATMD. 

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 USEPA 

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://www2.epa.gov/pesticidereevaluation.

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. 

1.2 Updates to the Work plan

Since the publication of the ATMD Preliminary Work Plan (PWP), the agency has made the 

following updates: 

 Updated the timeline in Table 2, the “Anticipated Registration Review Table.”

 Deleted “Guidance for Commenters” section.

 Updated Section 7, “Next Steps.”

 Added Appendix E, which includes the agency’s response to comments submitted 

regarding the PWP.
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 Corrected formatting and typographical errors.

The agency received one submission during the public comment period on the initial docket. See 

Appendix E for the agency’s response to this comment.

Comments received did not result in a modification to the anticipated data needs for the ATMD

work plan. This document makes final the work plan for the ATMD registration review process.

1.3 Case Overview

The Preliminary Work Plan (PWP) for ATMD was published on December 19, 2014, and the 60-

day comment period ended on February 17, 2015. The agency received one submission during the 

public comment period on the initial docket. Documents associated with this registration review 

case can be viewed at http://www.regulations.gov in docket EPA-HQ-OPP-2014-0656. Tables 1 

and 2 below summarize the issues relevant to this registration review case and the anticipated 

registration review schedule.

Table 1 – Anticipated Risk Assessments for Registration Review

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 6 for details)

Dietary (food) No (see 3.2.1) None None None 

Dietary (drinking water) Yes 2/10/2014

1 Updated

Developmental toxicity, reproduction and 

fertility effects, neurotoxicity, chronic 

toxicity, and carcinogenicity

(Note: these data exist, however EPA does 

not have access to the full reports)

Occupational Handler

(Liquid Products) No (see 3.3.1) 2/10/20141 None None – closed loading and delivery systems 

are used, exposure is minimal

Occupational Handler

(Solid Products) No (see 3.3.1) None None None – products are pellets/balls .25 to 4 

inches in diameter

Residential Handler and 

Post Application No (see 3.3.2) None None None – no residential exposure from registered uses

Aggregate No (see 3.4.1) None None None – exposure is only through drinking 

water

Cumulative No (see 3.4.2) None None None – no common mechanism identified

Tolerance Review No (see 1.6.1) None None None – all EPA registered uses are non-food
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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 6 for details)

Ecological Yes 2/10/20141 Updated

Aerobic aquatic metabolism, anaerobic 

aquatic metabolism, leaching-adsorptiondesorption, ready biodegradability, porous 

pot, simulation test—activated sludge units, 

simulation test—primary and ultimate, 

biodegradability, activated sludge respiration 

inhibition (ASRI), cyanobacteria toxicity, and 

whole sediment subchronic toxicity—

freshwater amphipod

1 U.S. EPA, February 10, 2014

The alkyl trimethylenediamines in this case are used primarily as microbiocides, bactericides, or 

molluscicides in industrial cooling water systems (recirculating and once-through) and for oilfield 

uses. The ATMD case is comprised of pesticidal active ingredients identified under four PC codes. 

The most recent risk assessment for ATMD (including both human health and 

ecological/environmental fate assessment) was completed on February 10, 2014 in support of a 

proposed new use to control bio-fouling in once-through cooling systems and recirculating cooling 

towers. For this assessment, the agency received summaries and not full studies for several key 

toxicity studies and default assumptions were used in lieu of some environmental fate and 

ecological studies. While the information for this risk assessment was adequate to add a new use 

to the existing registration and label, the risk assessment planned for registration review will cover 

all uses so that the agency can determine whether the active ingredients continue to meet the 

standard for registration as well as allow the agency to make endangered species determination. 

Findings and conclusions from this risk assessment are summarized in the memorandum “Risk 

Assessment for the Proposed Registration of the New Use of ATMD to Control Bio-fouling in 

Once-Through Cooling Systems and Recirculating Cooling Towers” (USEPA, 2014, decision 

number 478290). 

The agency has created the following estimated timeline for the completion of ATMD registration 

review.

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 2014-12 2014-12-19

Close Public Comment Period 2015-02 2015-02-17

Phase 2: Case Development 

Issue Final Work Plan 2015-06 2015-06

Issue Data Call-In (DCI) 2016-06

Receive Data to be Considered in Risk Assessment 2020-06

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2021-12

Close Public Comment Period 2022-01
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Phase 3: Registration Review Decision and Implementation 

Open 60-Day Public Comment Period for Proposed Decision 2022-06

Close Public Comment Period 2022-08

Issue Final Decision 2022-12

Begin Post-Decision Follow-up 2022

Total (years) 8

*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).

1.4 Chemical Identification and Properties

Table 3 presents the chemical and physical properties of the active ingredient(s) to be assessed in 

case 3014, which consists of four chemicals: N-(coco alkyl)trimethylenediamine (PC code

067301), 1-(Alkyl* amino)-3-aminopropane monoacetate *(as in fatty acids of coconut oil) (PC 

code 067302), 1-(Alkyl* amino)-3-aminopropane *(42%C12, 26%C18, 15%C14, 8%C16, 

5%C10, 4%C8) (PC code 067310), and 1-(Alkyl* amino)-3-aminopropane diacetate *(as in fatty 

acids of coconut oil) (PC code 067313). Throughout this document each of the ATMD chemicals 

will be referred to by PC code. In addition to the aforementioned four PC codes, previously the 

ATMD case (case 3014) also included 1-(Alkyl* amino)-3-aminopropane hydroxyacetate *(as in 

fatty acids of coconut oil) (PC code 067309), however this chemical will not be assessed as part of 

ATMD’s registration review since there are no registrations for this chemical. A more detailed 

presentation of the chemical and physical properties with data citations may be seen in Appendix 

D. 

Table 3 – Chemical Identification and Product Chemistry of ATMD Chemicals

Property OCSPP Guideline 

No. (unless stated)

067301 067302 067310 067313

CAS No. None 61791-63-7 61791-64-8 68155-37-3 61791-64-8

Molecular weight 

(grams/mol)

None 259.4 276 283.4 

(200-340 )

283.4 

(200-340 )

Water solubility 

(mg/L)

830.7840 ~10 Miscible 40,000 40,000 mg/l

Vapor Pressure 

(VP) (mm Hg)

830.7950 2.88 x 10-4 1.3 x 10-4 1.3 x 10-4 1.3 x 10-4

Henry’s Law (atm 

m3 mol-1)

1

None (calculated) 9.83 x 10-6 4.7 x 10-9 1.2 x 10-9 1.2 x 10-9

Log P (unitless) 830.7550 0.2 Not applicable for polar compounds

UV Visible 

absorption (nm)

830.7050 Limited sorption of UV light

pK 830.7370 Not determined2 Complete disassociation in water

1

[Vapor Pressure (mm Hg) * molecular weight (grams/mol)] / [760 * water solubility (mg/l)]

2 Water solubility too low to run test

 
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1.5 Use/Usage Description

1.5.1 Registrations

There are nine EPA-registered active products that contain one of the ATMD chemicals as an 

active ingredient (a.i.). One of these products is a technical/formulation intermediate product and 

the other eight products are end use products (EUPs). Seven of the EUPs are liquids and one EUP 

is a solid. The solid product is formulated as pellets/balls that range in diameter from 0.25 to 4 

inches. The products are listed in Table 4. 

Table 4 – ATMD Registered Products by PC Code and Type

PC Code Chemical Name

Product Type

Formulation 

Intermediate End Use Total

067301 N-(coco alkyl)trimethylenediamine 1 2 3

067302 1-(Alkyl* amino)-3-aminopropane monoacetate

*(as in fatty acids of coconut oil) 0 4 4

067310 1-(Alkyl* amino)-3-aminopropane 

*(42%C12, 26%C18, 15%C14, 8%C16, 5%C10, 4%C8) 0 1 1

067313 1-(Alkyl* amino)-3-aminopropane diacetate

*(as in fatty acids of coconut oil) 0 1 1

1.5.2 Summary of Registered Uses

Table 5 presents a summary of the registered uses of the ATMD chemicals that will be assessed in 

this registration review. ATMD liquid products are applied using closed delivery methods to meter 

in or inject the product into the system being treated. The ATMD solid products are applied by 

open pour. 

Table 5 – ATMD Registered Uses

Use Application Method Application Rate

(PPM A.I.)

Industrial Processes and Water Systems

Commercial/Industrial Water Cooling Systems 

(Once Thru)

Meter in/Inject Liquids 0.042

Commercial/Industrial Water Cooling Systems 

(Recirculating) Meter in/Inject Liquids 143 (shock/slug)14 (continuous)

Disposal Systems Meter in/Inject Liquids 143 (shock/slug)

14 (continuous)

Fuels/oil storage tanks bottom water Meter in/Inject Liquids

Open Pour Solids 1.6 to 32

Oil Recovery Drilling Muds/Packer Fluids Meter in/Inject Liquids 64 to 722

Pipelines (non piggable1) Meter in/Inject Liquids 65

Secondary Oil Recovery Injection Water Meter in/Inject Liquids 8 to 212 (shock/slug)

14 to 400 (continuous)
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Waterfloods and Salt Water Disposal Systems Meter in/Inject Liquids 60 (shock/slug)

15 (continuous)

1 A non-piggable pipeline is a pipeline that cannot be negotiated by standard inspection tools (i.e. pigs). Some factors that preclude 

the use of standard inspection tools include over- or under-sized valves, repair sections in a different size, and short-radius or 

mitred bends.

1.5.3 Usage Information

No usage information is available in the Kline Biocides Report for ATMD.

1.6 Regulatory History

The first product containing an ATMD chemical as an active ingredient was registered in the United 

States in May of 1965. 

The agency completed a Reregistration Eligibility Decision (RED) for ATMD in September of 2007. 

The post-RED Product Specific Data Call-In (DCI) was issued June of 2010; no Generic Data Call-In 

was issued.

The most recent risk assessment for ATMD (including both human health and 

ecological/environmental fate assessment) was completed on February 10, 2014 in support of a 

proposed new use for one of the ATMD compounds (PC code 067301) to control bio-fouling in 

once-through cooling systems and recirculating cooling towers. For more information on this risk 

assessment, refer to Section 1.3.

1.6.1 Tolerance Information

For ATMD chemicals in this case, EPA has not established tolerances or exemptions from 

tolerances in/on raw agricultural commodities or processed food and feed products under the 

Federal Food, Drug and Cosmetic Act (FFDCA) Section 408. ATMD has been cleared as an 

indirect food use for conveyor lubricant (TOR No. 2012-001) by the US Food and Drug 

Administration (US FDA) under the Threshold of Regulation (TOR) Exemptions. Under this 

clearance, ATMD may be used “as a lubricant for use in the conveyance of beverage containers.”

The subjects of the TOR request can be used as a combined total level not to exceed 0.75 weight 

% in dispersions applied to the conveyor belt below the bottle opening.”

1.7 Incidents

1.7.1 Human Health 

Individual Incident Reports

Incidents that are rated as moderate (HC) or higher are reported in individual reports which 

include information regarding the causes of the incident and symptoms experienced. In the case of 

ATMD, three human health individual incident reports, which are ranked as HC, are listed in the 

OPP Incident Data System (IDS) for the years 2007, when the RED was written, to the present 

(search conducted on 9/18/14). All three incidents were caused by operator error during product 

transfer that caused the product to be sprayed out of the transfer hose and onto employees. In two 

of these incidents, the employees suffered ocular burns which were resolved after treatment. In the 
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third incident, the employees required over the counter medication after being decontaminated in a 

safety shower and examined in a hospital.

Aggregate Incident Reports

Incidents that are rated as minor (HD) or that cannot be rated (HE) are reported in aggregate 

reports which are listings of the incidents for a manufacturer or distributer over a certain time 

period (often quarterly). Typically these reports only contain basic information such as the date, 

location and product involved and more detailed information such the cause of the incident or 

symptoms experienced are not included. In the case of ATMD there are three aggregate incidents, 

all of which are HD, listed in the IDS for the years 2007 - when the RED was written - to the 

present (search conducted on 9/18/14). Two of these incidents occurred due to spillage or transfer 

pump failure while the cause of the third incident was not reported. The symptoms, ocular 

irritation and burning, were only reported for one incident. 

1.7.2 Ecological

No ecological incidents have been reported for the active ingredients in the ATMD case in the 

agency’s IDS as of September 1, 2014.

2 Anticipated Data Needs

The ATMD chemicals in this case span a range of uses and physical/chemical properties. The 

agency expects to require environmental fate data for all PC codes. Data for PC code 067301 are

anticipated to be required since it is the only ATMD chemical with relatively-limited water 

solubility (~10 mg/l, Table 3). The other ATMD chemicals are miscible in water (Table 3). For the 

miscible compounds (PC codes 067302, 067310, 067313), data may be generated on any of these 

PC codes to satisfy the environmental fate data requirements. PC code 067310 is anticipated to be 

used as the surrogate for miscible ATMD chemicals, because it is a high production volume 

(HPV) chemical. It also has the highest production volume of the chemicals in this case.

The agency conducted a risk assessment for use of 067301 in cooling water systems dated 

February, 2014. To fulfill the data requirement for biodegradability in a wastewater treatment 

plant, the registrant submitted a ready biodegradability study (MRID 49040207). However, since 

this study did not meet the criteria for ready biodegradability the agency could not consider 

removal via biodegradation during wastewater treatment as part of the overall removal used as an 

input to the E-FAST down-the-drain Industrial Release Module. Data is necessary to refine the 

risk assessment. The agency anticipates requiring a wastewater treatment plant biodegradation 

simulation test.

The risk assessment conducted for use of 067301 in cooling water systems dated February, 2014

was also considered for the human health data requirements. The registrant submitted summaries 

of toxicity studies conducted on analogs of ATMD, many of which were cited in a 2008 European 

risk assessment (European Union Risk Assessment Report, 2008). In accordance with guidelines 

published by the Office of Pesticide Programs on citation of open scientific literature 

(http://www.epa.gov/pesticides/science/lit-studies.pdf), information from the open literature 

should be presented as the full article and not a summary. Therefore, the agency anticipates the 
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need to obtain the full study reports for the toxicity studies cited in support of this risk assessment, 

or equivalent information to address the data requirements as listed in Table 6 below.

Since no environmental fate data for PC codes 067302, 067310, or 067313 have been submitted to 

the agency, environmental fate data listed in Table 6 are anticipated as being required, including: 

(1) aerobic aquatic metabolism; (2) anaerobic aquatic metabolism; (3) leaching-adsorptiondesorption; (4) biodegradability during wastewater treatment; and (5) activated sludge respiration 

inhibition. Since these compounds are polar chemicals that are miscible in water, an activated 

sludge sorption isotherm test is not anticipated to be required.

Table 6 below presents a summary of the data anticipated as being needed to support this 

registration review. 
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Table 6 – Anticipated Data Needs for the Registration Review of ATMD Chemicals

GLN Study Name Test Substance

Time 

Frame1

(Months)

Risk Assessment(s) Data 

Will Support

Use Site(s) Triggering 

Anticipated Data 

Requirement

Applicable Exposure Scenario

835.4300 Aerobic aquatic metabolism TGAI4 24 Ecological Cooling towers, oil-field uses Ecological Exposure - IPWS

835.4400 Anaerobic aquatic metabolism TGAI4 24 Ecological Cooling towers, oil-field uses Ecological Exposure - IPWS

835.1230 Leaching-adsorption-desorption TGAI5 12 Ecological Cooling towers, oil-field uses Ecological Exposure - IPWS

835.31102,3

835.3220

835.3240

835.3280

Biodegradability in WWTP TGAI4 12 Ecological Cooling towers, oil-field uses Ecological Exposure - IPWS

850.3300 Activated Sludge Respiration 

Inhibition (ASRI) TGAI4 12 Ecological Cooling towers, oil-field uses Ecological Exposure - IPWS

850.4550 Cyanobacteria toxicity TGAI4 12 Ecological Cooling towers, oil-field uses Aquatic environment - aquatic 

plants

850.1735 Whole sediment subchronic 

toxicity, freshwater amphipod TGAI6 12 Ecological Cooling towers, oil-field uses Aquatic environment - benthic invertebrates

870.3700 Developmental Toxicity7 TGAI 24 Dietary Cooling towers, oil-field uses Drinking Water

870.3800 Reproduction and Fertility 

Effects7 TGAI 48 Dietary Cooling towers, oil-field uses Drinking Water

870.6200 Neurotoxicity Study7 TGAI 12 Dietary Cooling towers, oil-field uses Drinking Water

870.4100 Chronic Toxicity7 TGAI 48 Dietary Cooling towers, oil-field uses Drinking Water

870.4200 Carcinogenicity7 TGAI 48 Dietary Cooling towers, oil-field uses Drinking Water

TGAI = Technical Grade Active Ingredient; IPWS = Industrial Processes and Water Systems. 

Footnotes 

1 The Time Frame is measured in months from DCI Receipt.

2 For PC codes 067302, 067310, and 067313, the results of the Activated Sludge Respiration Inhibition Test (ASRI) will determine which of these four biodegradation tests is/are

anticipated to be required. 
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 If the ASRI test EC50 is less than or equal to 20 mg/L, then either the (i) Biodegradation in Activated Sludge Study or (ii) Simulation Test - Aerobic Sewage Treatment: A. 

Activated Sludge Units or (iii) the Porous Pot Test is required. If the ASRI test EC50 is greater than 20 mg/L, then the registrant must conduct either: (i) Ready 

Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test - Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous Pot Test. 

 If the Ready Biodegradability study is conducted and passes, then no further testing is required. If, however, the antimicrobial fails the Ready Biodegradability study, then the 

a) Biodegradation in Activated Sludge or b) Simulation Test - Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study is required.

3 A ready biodegradability study (MRID 49040207) was conducted for PC code 067301, and based on the results, it was determined to not be readily biodegradable. As a result, a 

wastewater treatment plant biodegradation simulation test (GLN 835.3280) is anticipated to be required.

4 Data are anticipated to be required for all PC codes. For the miscible compounds (PC codes 067302, 067310, 067313), data may be generated on any of these PC codes to satisfy 

the requirement.

5 Data are not anticipated to be required for PC code 067301, because the agency has adequate data on leaching for this PC code. Data are anticipated to be required on any one of 

the other three PC codes. 

6 Data are anticipated to be required for PC code 067301 since it is the only compound expected to be found in sediments. Data are not required for the other three compounds 

which are expected to remain in the water column. 

7 These data exist, however EPA does not have access to the full reports. Data on any of the four PC codes (067301, 067302, 067310, 067313) may be submitted

to satisfy the requirement. 
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3 Human Health Risk Assessment

The agency anticipates the need to conduct a human health dietary (drinking water) risk 

assessment for ATMD. The agency expects to require additional data for use in conducting the 

registration review.

The most recent human health risk assessment for ATMD was completed on February 10, 2014 

in support of a proposed new use of ATMD (PC code 067301) to control bio-fouling in oncethrough cooling systems and recirculating cooling towers. Findings and conclusions from this 

risk assessment are summarized in the memorandum, “Risk Assessment for the Proposed 

Registration of the New Use of ATMD to Control Bio-fouling in Once-Through Cooling 

Systems and Recirculating Cooling Towers” (USEPA, 2014, decision number 478290). Based on 

the drinking water exposure and human health risk assessment performed by the agency in 

support of this registration decision, EPA did not identify risks of concern for the proposed use.

In the 2014 risk assessment, the information submitted for assessment of human health hazard on 

ATMD consisted largely of summaries of toxicity studies conducted in experimental animals. 

Many of these studies were cited from a 2008 European Union Risk Assessment document on 

certain ATMD chemicals (European Risk Assessment Report, Primary Alkyl Amines, 2008). 

OPP’s Open Literature guidance document (http://www.epa.gov/pesticides/science/litstudies.pdf) describes the adequacy of scientific literature studies submitted in support of a 

human health risk assessment. Information from the open literature should be presented as the 

full article and not a summary. All of the cited studies from the 2008 European Commission risk 

assessment were submitted as summaries only. This hinders a full hazard evaluation and doseresponse assessment of the mammalian toxicity data for ATMD. The agency anticipates 

requiring the full published articles for the toxicology data on ATMD or equivalent information 

to support the risk assessment for registration review of ATMD. 

3.1 Toxicological Endpoints

The existing toxicological endpoints for ATMD may need to be revised based on review of the 

published studies anticipated to be required for ATMD as noted in section 2. Table 7 presents the 

current endpoints used in the agency’s most recent risk assessment in support of the use of 

ATMD in once-through cooling towers. 

The information submitted by the registrant in support of the recent new use consisted of one 

submitted 90-day oral toxicity study (MRID 49092801) reviewed by the Office of Pesticide 

Programs’ (OPP) Antimicrobials Division, and summaries of toxicity studies on subchronic 

(MRID 49208808), developmental (MRID 49208809), reproductive (MRID 49208810), chronic 

toxicity (MRID 49208811), carcinogenicity (MRID 49208812), and neurotoxicity (MRID 

49208813) cited in a 2008 European risk assessment document (European Commission, 2008; 

information submitted under MRID 49208808). The studies cited in the 2008 European 

Commission risk assessment were conducted on certain ATMD structural analogs. The agency 
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has determined that the data on the ATMD analogs summarized in the 2008 European 

Commission risk assessment could be considered together with the data on ATMD, as the effects 

observed from toxicology studies conducted with these chemicals appear to be similar, and are 

related to the irritant properties of these chemicals. One difference appears to be the doses at 

which the effects are observed, with the diamine chemicals being more potent than the 

monoamine chemicals in causing irritant-like effects. Toxicity information also consists of a 

repeated dose toxicity study with developmental and reproductive screening (MRID 47646101) 

submitted on coco alkylamines (PC code 067301). Summaries of all toxicity studies are 

presented in Appendix A. 

Table 7 – Toxicological Endpoints for ATMD

Exposure 

Scenario

Dose Used in 

Risk Assessment 

(mg/kg/day)

Target Margin of 

Exposure (MOE), 

Uncertainty Factor (UF), 

FQPA Safety Factor (SF)

Study and Toxicological Effects

Dietary 

(drinking 

water)

0.4 mg/kg/day 100 (10x interspecies 

extrapolation, 10x intraspecies variation)

90-day oral toxicity study in rodents (MRID 

49092801)

LOAEL = 1.5 mg/kg/day, based on decrease in body 

weight gain and food consumption in males and 

histopathology changes in the male and female 

mesenteric lymph node, spleen, bone marrow 

(sternum) and trachea.

3.2 Dietary Exposure

The agency has previously conducted a dietary (drinking water only) exposure and risk 

assessment for ATMD (PC code 067301) (US EPA, 2014). However, since the agency has not 

conducted an analysis of potential drinking water exposure for the other uses and chemicals 

considered in this case, a revised assessment is anticipated as being needed during registration 

review pending review of any submitted environmental fate data. Although ATMD has been 

cleared by FDA as a conveyor lubricant for use in the conveyance of beverage containers, a 

dietary (food) assessment is not required since this use pattern does not have a registration under 

FIFRA. 

3.2.1 Food

Based on reviewing the current labels, there are no uses expected to result in direct or indirect 

dietary (food) exposure. Residue chemistry data are not anticipated to be required at this time.

3.2.2 Drinking Water

Based on an assessment of the potential for exposure and risk to humans from ingestion of 

drinking water conducted by the agency in 2014 (USEPA, 2014), potential risks to humans from 

ingestion of drinking water were evaluated and determined to be negligible, for the use of PC 

code 067301 in once-through cooling systems and recirculating cooling towers. 
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The agency has not conducted an analysis of potential exposure and risk from ingestion of 

drinking water by humans for the other uses and chemicals considered in this case. However, an 

evaluation of potential exposure will be conducted to draw any conclusions regarding potential 

risk from ingestion of drinking water by humans for the other uses and chemicals within the 

scope of this case.

In assessing potential exposures and risks to humans from ingestion of drinking water, the

agency anticipates using information on any one of the three miscible compounds (PC codes 

067302, 067310, and 067313) as a surrogate for the others. 

3.3 Occupational and Residential Exposures

Occupational and residential exposures were most recently assessed in the risk assessment for 

the proposed once through cooling tower use of ATMD (US EPA, 2014). It was determined that 

occupational exposures were not of concern due to the use of closed systems and that residential 

exposures were not of concern because the cooling tower use would not result in residential 

exposures. 

3.3.1 Occupational Exposures 

The agency does not anticipate the need to revise occupational handler exposures for the liquid 

products presented in the 2007 RED or the 2014 risk assessment. Occupational exposures are 

expected to be minimal if closed loading and delivery systems are used for the liquid products. 

Occupational handler exposures were not assessed for the solid product (49245-5) - registered in 

2008-which can be open poured; however, these exposures are anticipated to be minimal because 

of the nature of the solid product formulation (pellets/balls 0.25 to 4 inches in diameter).

3.3.2 Residential Exposures

There are no registered residential uses for ATMD, thus, there are no expected residential 

exposures. 

3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures 

An aggregate assessment was not conducted in the 2007 RED based on the lack of expected 

exposures in food, drinking water, or from residential uses. Although the agency will assess the 

potential for drinking water exposures, there are no other residential exposures expected to 

develop an aggregate assessment (e.g., the agency anticipates that the use of ATMD as lubricant 

for the conveyance of beverage containers will result in negligible residue transfer to food 

items). Therefore, agency does not anticipate the need for an aggregate assessment for the 

registered uses of ATMD.
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3.4.2 Cumulative Exposures 

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

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

common mechanism of toxicity finding as to ATMD and any other substances and ATMD does 

not appear to produce a toxic metabolite produced by other substances. For the purposes of this 

preliminary risk assessment, therefore, EPA has not assumed that ATMD 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 previously conducted a risk assessment which concluded that N-(cocoalkyl) 

trimethylenediamine (PC code 067301) used in once-through cooling systems and recirculating 

cooling towers would not be expected to pose higher risks to aquatic organisms than alternative 

chemical substances that could be used as biofoulants in recirculating cooling towers and oncethrough cooling systems. The agency has not conducted a risk assessment for the other 

chemicals and uses in this case (i.e., case 3014). 

The agency has not previously conducted a complete endangered species determination for any 

uses of the ATMD chemicals in this case. The ecological risk assessment planned during 

registration review will allow the agency to determine potential acute and chronic risks to aquatic 

organisms potentially exposed in the aquatic environment. The risk assessment will allow the 

agency to determine whether the uses of ATMDs have 'no effect' or 'may affect' federally listed 

threatened or endangered species (listed species) or their designated critical habitats. 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 Assessment

The alkyl trimethylenediamines in this case are used primarily as microbiocides, bactericides, or 

molluscicides in industrial cooling water systems (recirculating and once-through) and for 

oilfield uses. Based on the chemical structure, as a group, ATMD chemicals are not susceptible 

to degradation by abiotic processes (i.e., hydrolysis and photodegradation in water).

3 Acceptable 

data demonstrating biotic degradation in the ambient environment have not been submitted for 

any ATMD chemicals and are anticipated to be required during registration review (835.4300 

and 835.4400, see Table 6). 

The only ATMD chemical for which environmental fate data have been submitted is N-

(cocoalkyl) trimethylenediamine (PC code 067301). The environmental fate data for this 

 

3 Appendix B
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chemical indicate that it is less water soluble than the other compounds in this case, and is 

strongly sorbed to soil, sediment, and sludge.

Based on MRID 49040210, there is limited potential for bioconcentration of N-(cocoalkyl) 

trimethylenediamine in fish. 

Based on the vapor pressure and Henry’s Law values in Table 3, none of the ATMD chemicals 

are expected to move into the air in significant quantities from the registered use sites.

4.1.1 Water Quality

The ATMD chemicals are not identified as a cause of impairment for any water bodies listed as 

impaired under section 303(d) of the Clean Water Act.

4

In addition, Total Maximum Daily Loads

(TMDL) have not been developed for the ATMD chemicals.

5 More information on impaired 

water bodies and TMDLs can be found at EPA’s website.

6

4.2 Environmental Exposure Pathways

Based on the summary of registered uses of the ATMD chemicals presented in Table 5, the

physical/chemical properties in Table 3, and the environmental fate data presented in Appendix 

B, the agency has determined that some environmental exposure to ATMD chemicals can occur 

from the industrial cooling water system and oilfield uses. For the industrial cooling water 

system uses (recirculating and once-through), environmental exposure to ATMD chemicals can 

potentially occur from effluent that leaves the plant or from sludge from WWTPs that sorb 

ATMD chemicals and is subsequently land-applied. For the oilfield uses, the primary exposure 

would be to surface water from produced water in storage ponds or produced water that is treated 

in a WWTP and subsequently discharged. Ground water contamination can also potentially 

occur if a well is not cased properly, if a storage pond is not lined, or if a liner fails. Aquatic 

organisms may be at risk if exposed to ATMD chemicals in surface waters and aquatic sediments

downstream from facilities that discharge ATMD chemicals to surface water. 

Based on the uses of ATMD chemicals listed in Table 5, the agency has created conceptual 

models for potential routes of environmental exposure which are included in “Conceptual 

Models for Environmental Exposure Pathways of Antimicrobial Pesticides” (EPA-HQ-OPP2014-0638-0002), found at www.regulations.gov in docket EPA-HQ-OPP-2014-0638. For oncethrough cooling water systems and recirculating cooling towers, refer to slides 13 and 14. For oil 

recovery drilling muds/packer fluids, and secondary oil recovery injection water, refer to slides 

19 and 20. For non-piggable pipelines, refer to slide 23. All relevant routes of environmental 

exposure will be considered in the risk assessment.

 

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

5http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

6 http://www.epa.gov/owow/tmdl/
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4.3 Ecological Effects Assessment

4.3.1 Mechanism of Action

The agency is not aware of the mode of action of ATMD chemicals for ecological effects.

4.3.2 Available Endpoints from Submitted Studies 

Acute and chronic toxicity data from registrant-submitted studies (850 OCSPP Harmonized Test 

Guidelines) are used to evaluate the potential effects of the ATMD chemicals to plants and 

animals. All available ecotoxicity endpoints are tabulated in Appendix C. For most requirements, 

data are bridged among the four PC codes. However, PC code 067301 is the only ATMD 

expected to bind to soils and sediments; therefore, sediment toxicity tests are anticipated to be 

needed only for that PC code.

OPP uses the most sensitive endpoints for assessing risks. The available endpoints for the 

ATMD chemicals are provided in Table 9. Data gaps exist for cyanobacteria (850.4550) for all 

ATMD compounds, and a freshwater amphipod (850.1735) for PC code 067301 only. These data 

are anticipated to be required. When those data become available, they may be used in lieu of the 

tabulated values for nonvascular aquatic plants and sediment-dwelling invertebrates if they are 

found to be more sensitive. See Appendix C for more information on these data gaps.

 

Table 8 – Available Ecological Effects Endpoints

Receptor 

Group

Test 

Material

Risk 

Scenario Toxicity Endpoint Reference

Freshwater fish TGAI Acute LC50 = 0.03 mg ai/L 133265 and 

41786601

Freshwater fish TGAI Chronic NOAEC = 0.004 mg ai/L 49208804

Freshwater invertebrates TGAI

Acute EC50 = 0.051 mg ai/L 41786602

Chronic NOAEC = 0.016 mg ai/L 49040208

Estuarine/marine fish TGAI

Acute LC50 = 0.155 mg ai/L 41786604

Chronic Not required --

Estuarine/marine 

invertebrates TGAI

Acute EC50 = 0.019 mg ai/L 41786605 and 

41786603

Chronic Not required --

Aquatic plants, vascular TGAI EC50 and 

NOAEC

EC50 = 0.123 mg ai/L

NOAEC = 0.020 mg ai/L 49040213

Aquatic plants, 

non-vascular TGAI EC50 and 

NOAEC

EC50 = 0.0052 mg ai/L

NOAEC = 0.0024 mg ai/L 49040216

Sediment-dwelling

invertebrates TGAI Subchronic EC50 = 188 mg ai/kgNOAEC = 16 mg ai/kg 49040211

Birds TGAI Acute LD50 = 0.24 mg ai/kg 470013023
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4.3.3 Open Literature 

Open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database. 

The ECOTOX database will be searched when the risk assessment is prepared. Any acute or 

chronic endpoints more sensitive than currently available data will be evaluated in the risk 

assessment. Use of open literature is discussed in more detail on the agency’s website: 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_

reregistration_workgroup/esa_evaluation_open_literature.htm (U.S. EPA, May 16, 2011).

4.4 Exposure Analysis Plan

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

The agency plans to use the General Population and Ecological Exposure from Industrial 

Releases module of E-FAST (Exposure and Fate Assessment Screening Tool) to determine the 

number of days of exceedance of ATMD concentrations of concern for aquatic organisms to 

predict the potential for exposures and risks to aquatic organisms downstream of facilities that 

release ATMD chemicals to surface water. 

All end-uses for this case are industrial uses. Since a screening tool to analyze exposures and 

ecological risk from industrial uses is not currently available, as stated in section 4.4.2, a 

screening-level down the drain analysis of these uses is not within the scope of this preliminary 

work plan.

The agency has conducted a risk assessment for ATMD (PC code 067301) used to control biofouling in once-through cooling systems and recirculating cooling towers (USEPA, 2014). To 

refine this assessment and to analyze potential exposures and ecological risks from other

industrial uses, the agency expects to use the General Population and Ecological Exposure from 

Industrial Releases Module of E-FAST. The input data required to run this module include: (1) 

percent removal of antimicrobial during wastewater treatment from biodegradation and ASRI 

studies; (2) environmental releases of antimicrobial to surface water in kg/site/day; (3) annual 

number of days of release of antimicrobial to surface water; (4) Standard Industrial Classification 

code(s) to represent the industrial uses being assessed; and (5) concentrations of concern for 

aquatic animals and plants. The method used to estimate environmental releases of antimicrobial 

to surface water will be based on the specific end-use being evaluated. 

4.4.2 Screening Level Down-the-Drain Analysis

No screening-level Down-the-Drain analysis was performed for this case since all uses for this 

case are industrial uses. Results from the screening Down-the-Drain module of E-FAST are only 

applicable for chemicals that are incorporated in products that are released down-the-drain to 

domestic wastewater treatment facilities. 
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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 reregistration decision for ATMD, 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), ATMD is subject to the 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

identified for EDSP screening was published on June 14, 20137and includes some pesticides 

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

construed as a list of known or likely endocrine disruptors.

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

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

website.8

 

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

chemicals.

8 http://www.epa.gov/endo/
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6 Optional Label Changes

The agency invites any label amendments that could be considered to eliminate the anticipated 

need for EPA to require certain data, reduce the possibility that EPA’s planned risk assessments 

overestimate risk due to reliance on conservative assumptions, and/or improve label clarity.

7 Next Steps 

A DCI will be developed regarding the data needs listed under the “Anticipated Data Needs” 

section of this document. The agency expects to issue the DCI by June 2016.
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8 References 

MRID 42022502. Sinning, D. December 2, 2010. Physical and Chemical Characteristics of 

Mexel 432/0: Color, Physical State, Odor, Oxidation/Reduction: Chemical 

Incompatibility, Flammability, pH, Viscosity, and Relative Density. Project Number: 

4800/01. Unpublished study prepared by Case Consulting Laboratories, Inc. 9 p. 

MRID 43022902. Ellison, F. (1993) [N-(coco alkyl)trimethylenediamine]: Physical and 

Chemical Characteristics of [N-(coco alkyl)trimethylenediamine]: Physical State, Boiling 

Point, Specific Gravity, Solubility, Vapor Pressure, pH, Stability, Oxidizing or Reducing, 

Explodability and Viscosity: Final Report: Lab Project Number: 00459-002. Unpublished 

study prepared by Case Consulting Labs, Inc. 19 p.

MRID 48486702. Sinning, D. May 16, 2011. Physical and Chemical Characteristics of [N-

(coco alkyl)trimethylenediamine]: Color, Physical State, Odor, Stability, pH, UV/Vis, 

Boiling Point, Density, Dissociation Constant, Octanol/Water Partition Coefficient and 

Solubility: Final Report. Project Number: 4870/02. Unpublished study prepared by Case 

Consulting Laboratories, Inc. 32 p.

MRID 49040202. Murrell, J.R. and W. B. Nixon. April 5, 2012. Determination of the 

Ultraviolet-Visible Absorption Spectrum of [N-(coco alkyl)trimethylenediamine]. 

Wildlife International Project No. 709C-103. Unpublished study conducted by Wildlife 

International, Easton, MD, and submitted by Mexel Industries, Arlington, VA.

MRID 49040203. Farnback, M. July 16, 2012. Determination of the Partition Coefficient (1-

octanol/water) for [N-(coco alkyl)trimethylenediamine]. OCSPP Guideline 830.7550. 

Unpublished study performed by Casco Adhesives AB, Sweden, and submitted by Mexel 

Industries, France.

MRID 49040204. Velea, Luminita. February 26, 2013. Water Solubility for Mexel 432/P, EPA 

Reg. No. 84034-1. Unpublished study performed by Technology Sciences Group, 

Washington, DC, and submitted by Mexel Industries, Arlington, VA.

U.S. EPA. 2002. ECOTOX User Guide: ECOTOXicology Database System. Version 3.0. 

Available: http://www.epa.gov/ecotox/

U.S. EPA. September, 2007. Reregistration Eligibility Decision (RED) for 

Alkyltrimethylenediamines (Case 3014). EPA 739-R-07-004.

U.S. EPA. May 16, 2011. Evaluation Guideline for Ecological Toxicity Data in the Open 

Literature. 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_s

pecies_reregistration_workgroup/esa_evaluation_open_literature.htm
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U.S. EPA. High Production Volume Information System (HPVIS). http://www.epa.gov/hpvis/

U.S. EPA. 2012. EPI-Suite 4.11. http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

U.S. EPA. February 10, 2014. Risk Assessment for the Proposed Registration of the New Use of 

ATMD to Control Bio-fouling in Once-Through Cooling Systems and Recirculating 

Cooling Towers. Decision Number 478290 (D415622, D415970, D411969, D416478).
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Appendix A Toxicology Profile

Acute Toxicity for Product Labeling 

There are no acceptable acute toxicity studies for the technical grade ATMD chemicals. 

Previously submitted studies cited in the ATMD RED for lower concentrations of ATMD show 

that for eye and skin irritation, ATMD is assigned Toxicity Category I. Thus it is not necessary 

to conduct eye and skin irritation studies with the technical grade, as a Category I will also be 

assigned for these effects. Acute oral, acute dermal, acute inhalation, and dermal sensitization 

studies are being called in through the post-RED product specific DCI. 

Table 1 – Acute Toxicity Studies for ATMD

Guideline No./ Study 

Type MRID No. Results Toxicity Category

870.1100/ 

Acute oral toxicity N/A

No studies were submitted and studies in the literature do not 

meet applicable guidelines. 

Unknown 

870.1200/ 

Acute dermal toxicity N/A Unknown

870.1300/ 

Acute inhalation toxicity N/A Unknown

870.2400/ 

Acute eye irritation N/A Corrosive I

870.2500/ 

Acute dermal irritation N/A Corrosive I

870.2600/ 

Skin sensitization N/A No study is available. This study was identified as a data gap in the RED. Unknown

N/A=Not available 

SUBCHRONIC TOXICITY

An acceptable 90-day oral toxicity study (MRID 49092801) was submitted and reviewed. In this 

study, N - (coco alkyl) trimethylenediamine (94% a.i., Batch No.: S000904) was administered to 

10 Wistar RjHan:WI rats/sex/dose via oral gavage as a suspension at dose levels of 0 (C), 0.1, 

0.4, 1.5, or 6 mg/kg/day for 7 days/week for a period of 90 days at a volume of 4 ml/kg. There 

were two recovery groups consisting of 5 animals per sex: one was observed for 28 days and one 

for 90 days following the last compound administration. 

Test item related clinical signs were observed in 1.5 and 6.0 mg/kg/day groups and recovery 

groups. Signs included slight to severe salivation, half-eyelid closure, vocalization, temporary 

stertorous respiration, oral and nasal discharge, dyspnea, weight loss and piloerection.

Three mortalities in the main groups, (two female from 6.0 and one male from 1.5 mg/kg/day 

groups) and 2 mortalities in high dose females of the 90-day recovery group were observed. 

Dosing error might have been the cause in three of the animals. No cause of death could be 

established in the remaining two females treated at 6 mg/kg/day.

During the treatment period (days 1 to 90 in the main study and recovery high dose group male 

animals), there was a statistically significant decrease in overall body weight gain [33%] and 
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food consumption [16%] compared to the corresponding controls. No change was seen in the 

females. 

No test item related effect occurred in hematology and urine parameters and clinical 

biochemistry parameters in male and females of any group except decreases in total protein in 

the 1.5 and 6.0 mg/kg/day females when compared to the control. 

No effect on organ weight in male and female animals of treated group and recovery group was 

observed which could be considered as a treatment related effect except a decrease in absolute 

liver weights in 6.0 mg/kg/day males, increase in relative kidney weights in 28-day recovery 

males, increase in relative adrenal weights in 6.0 mg/kg/day male and females, and increase in 

relative epididymides weight in 6.0 mg/kg/day males. No histopathology changes were noted 

that could account for these changes.

At the terminal sacrifice of the main study and recovery animals, macroscopic findings observed 

were considered to be spontaneous and not treatment related. Histopathologically, test itemrelated changes were seen in the small intestine (ileum and jejunum), mesenteric lymph node, 

spleen, bone marrow (sternum) and trachea at 1.5 mg/kg/day and above. After the 28-day 

recovery period, treatment- related changes in the jejunum, ileum and mesenteric lymph node 

were still present in animals of this dose group. Changes noted in the spleen had partially 

regressed and bone marrow (sternum) and tracheal changes had fully regressed. After 90 days of 

recovery, test article-related changes in the jejunum, ileum and mesenteric lymph node had 

partially regressed. No test article-related changes were noted in the spleen, bone marrow

(sternum) and trachea.

The NOAEL is 0.4 mg/kg/day. The LOAEL is 1.5 mg/kg/day based on a decrease in body 

weight gain and food consumption in males and histopathology changes in the 

gastrointestinal tract in males and females.

DEVELOPMENTAL TOXICITY

A developmental toxicity study was not conducted for N-(coco alkyl)trimethylenediamine [also 

referred to as N-coco 1,3-diaminopropane]. Instead, the registrant cited a study summary that 

was presented in the 2008 European Union Risk Assessment Report for tallow alkyl amines. 

This study was conducted on octadecenylamine, whose structure is shown below:

The summary of this study is presented below:

“In the main study, groups of 28 pregnant females were treated orally (gavage) with dosages of 

10, 40 or 80 mg/kg/day or with the vehicle (Mazola corn oil) during gestation days 6 to 15. 

During the study animals were examined daily. Any clinical signs of toxicity including physical 

or behavioral abnormalities were recorded. Individual body weights and food consumption were 

recorded on gestation days 0, 6, 9, 12, 16, and 20. Two animals in each group were selected to be 
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sacrificed and necropsied after treatment on gestation day 15 to determine the appearance and 

severity of gastrointestinal tract irritation. On gestation day 20 caesarean section was performed 

on all surviving animals. The numbers of viable fetuses, early and late resorptions as well as the 

number of corpora lutea were recorded. Fetuses were examined for external, visceral and skeletal 

abnormalities.”

“All animals survived to scheduled sacrifice. Outward clinical signs of toxicity were observed at 

the 40 and 80 mg/kg/day dose levels. The observations most likely indicated a generalized 

irritative effect of the test substance as characterized by rales, salivation, unkempt appearance 

and changes in the amount, color and consistency of the feces. However, no other signs of 

treatment-related gastrointestinal irritation or other internal changes were observed at the 

gestation day 15 and 20 necropsies. More pronounced signs of toxicity were apparent only in the 

80 mg/kg/day dose group and included emaciation, rough coat and dark red material around the 

eyes, nose and/or mouth. Similar clinical signs were infrequently noted during the post-dose 

observations. Dose-dependent body weight loss (during gestation days 6-9) or reduced weight 

gain (during gestation days 12-16), along with a corresponding reduction in food consumption 

occurred during the treatment period in the 40 and 80 mg/kg/day dose groups. Net body weight 

gain (adjusted for gravid uterine weight) was also lower at these levels. Following cessation of 

treatment (days 16-20), increase in weight gain and food consumption were noted at both dose 

levels. No such effects were observed in the dose group treated with 10 mg/kg/day. Caesarean 

section data obtained from the treated groups did not reveal any meaningful differences 

(concerning number of corpora lutea, implantation sites, viable fetuses, fetal sex and fetal 

weight) when compared with the controls. Fetal evaluations of type and frequency of 

malformations and variations did not reveal any indications for a treatment related teratogenic 

effect. In summary, oral administration of octadecenylamine to pregnant rats produced dosedependent maternal toxicity in the 40 and 80 mg/kg/day dose groups. No indications of an 

embryotoxic, fetotoxic or teratogenic effect were observed at any tested level.” 

“A NOAEL/maternal toxicity of 10 mg/kg/day and a NOAEL/developmental

toxicity of > 80 mg/kg/day can be derived from the study.”

REPRODUCTION AND FERTILITY EFFECTS

No data on reproduction and fertility effects were submitted for the active ingredient N-(coco 

alkyl)trimethylenediamine [also referred to as N-coco 1,3-diaminopropane]. Instead, the 

registrant cited a summary of a study conducted on tallow alkyl amines. This study was 

conducted according to OECD test guideline 421 (developmental/reproductive screening assay). 

The summary of this study is presented below.

Groups of 10 rats (Crl:CD (SD) BR) per sex were treated with dosages of 0, 12.5, 50, and 150 

mg/kg/day by gavage (administration volume 10 ml/kg/day) using sesame oil as a vehicle. Males 

were treated daily from 14 days prior to mating until the end of the mating period for a maximum 

of 28 days. Females were treated daily for 14 days before start of the mating period, throughout 

the same, during pregnancy and until day 3 of lactation. The animals were mated one male with 

one female. 
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At daily doses of 150 mg/kg/day 6/10 males and 5/10 females died between day 9 and day 25 of 

treatment (during the premating and mating period). At daily doses of 50 mg/kg/day 1/10 males 

and 1/10 females died on day 13 respectively on day 24 of treatment. No animals died at 12.5 

mg/kg/day, and in the control group 1 female died by accident.

Clinical observations at 150 mg/kg/day revealed salivation after treatment, hunched posture and 

in some cases soft stools and piloerection. The only clinical sign present at 50 mg/kg/day was 

salivation. No changes were seen at 12.5 mg/kg/day.

Body weight loss of about 22 g at the 150 mg/kg/day dose group and statistically significant (p > 

0.01) lower body weight gain at the 50 mg/kg/day dose group during the premating period 

together with a lower mean food consumption was observed in the males. Also in the females 

body weight loss of about 17 g at the 150 mg/kg/day dose group and statistically significant 

lower body weight gain at the 50 mg/kg/day dose group together with a lower mean food 

consumption during the premating period was observed.

At sacrifice of the parental animals organ weights of ovaries, testes and epididymides were 

determined from all experimental groups. Histopathology was carried out on testes, 

epididymides and ovaries of the controls and of the animals of the 150 mg/kg/day dose group. A 

statistically significant (p> 0.01) lower absolute and relative weight of epididymides and a 

statistically significant (p> 0.01) higher value of relative testis weight was observed at 150 

mg/kg/day. No significant differences were noted in ovary weights among the various 

experimental groups. Histopathology of testes and epididymides of high dose group animals did 

not show any compound-related changes. In particular, no changes were seen in the testicular 

staging performed in the PAS-hematoxylin stained sections of final sacrificed animals of control 

and of the high dose groups. In the ovaries, moderate increased frequency of atrophic corpora 

lutea was seen in the animals of the high dose group which died or were sacrificed, compared to 

the controls, this finding was considered a secondary effect to the decrease in body weight 

growth induced by treatment in this group. At the dosages of 150 mg/kg/day only 3 females out 

of 7 mated females had positive vaginal smears and of these only one was pregnant, but with 

only implantation sites and no live pups. At this dosage level also the mean pre-coital interval 

was longer (13.4 days) than that of the control group (2.3 days). With regard to the mating index 

in the control, the 12.5 and the 50 mg/kg/day dose level groups 9/9 (100%), 9/10 (90%) and 9/9 

(100%) mated females were sperm positive. With regard to the fertility index 9/9 (100%), 8/10 

(80%) and 7/9 (78%) of the mated females became pregnant in the control, the 12.5 and the 50 

mg/kg/day dose groups. Mean pre-coital time and parturition were unaffected in the low and mid 

dose treated groups.

With regard to the conception rate in the control, the 12.5 and the 50 mg/kg/day dose groups 9/9 

(100%), 8/9 (89%) and 7/9 (78%) of the sperm positive females became pregnant and delivered 

live pups. Numbers of corpora lutea had not been determined during this study. Thus, any preimplantation loss was not evaluated. Staining for the presence of implantation sites was only 

performed with the uteri of apparently non-pregnant females. The mean number of visible 

implantation sites per dam in the control, the 12.5 and the 50 mg/kg/day dose level groups were 

17.6, 13.9 and 15.0. There were no stillborns or litters with only implantations in the control, 

low, and mid dose groups. The mean number of total pups born per litter was 16.9, 12.3 and 14.3 
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in the control, the 12.5 and the 50 mg/kg/day dose groups. Thus, the mean litter index for postimplantation loss was calculated to 3.4, 9.9 and 4.5% in the control, the low and the mid dose 

groups.

No effects were noted on the pup sex ratio. No abnormalities were observed in any pup either at 

birth or at autopsy on day 4 of lactation neither in the 12.5 nor in the 50 mg/kg/day dose groups. 

Lower mean values of live born per litter and of pups per litter alive at day 4 were found for both 

the low and the intermediate dose groups in comparison to those of the control group, however, 

the decreases were not dose dependent and the differences were statistically significant for the 

12.5 mg/kg/day dose group only. Thus, these findings were considered unlikely to be related to 

the compound. A slightly lower pup body weight was observed in the 50 mg/kg/day dose group 

in comparison with the control group at birth and at day 4 of lactation but not for the pups of the 

12.5 mg/kg/day dose group.

Based on findings of general toxicity (death, clinical signs, reduced body weight gain) at 

daily dosages of 50 mg/kg/day a NOEL/systemic toxicity of 12.5 mg/kg/day can be derived 

from the study. Based on the findings of a lower fertility index and a lower conception rate 

at daily dosages of 50 mg/kg/day a NOEL/fertility of 12.5 mg/kg/day can be derived from 

the results of this screening study.

In addition to the above cited study, a combined repeated dose toxicity study with 

reproduction/developmental toxicity screening (performed according to OECD guideline 422) 

was conducted with coco alkylamine (CAS # 61788-46-3) and was submitted and reviewed by 

the Office of Pesticide Programs (MRID 47646101). Coco alkyl amine was assessed as part of a 

risk assessment conducted in 2009 by the Health Effects Division of OPP for inert uses of a 

group of primary alkyl amines in pesticide formulations. Note that coco alkylamine is a 

chemical listed in the 2008 European Union risk assessment, but is not listed in the OPP RED for 

ATMD. 

Structure:

MRID 47646101 Study Summary

In a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening 

Test (MRID 47646101), Amines, coco alkyl (CAS # 61788-46-3; Batch # 830668; 100.4% a.i.) was 

administered to 10 Crl:CD(SD) rats/sex/dose by gavage at doses of 0, 5, 20, 40 or 80 mg/kg/day. The 

vehicle and diluent were reverse osmosis deionized water and glacial acetic acid, respectively. Dosing 

began 14 days before the cohabitation period and continued through the day before sacrifice. Surviving 

male rats received at least 46 doses. For female rats, dosing continued through lactation day (LD) 4 for 

rats that delivered a litter or GD 24 for rats that did not deliver a litter. Females received a total of 38-42 

doses. Five animals/sex/group were tested in the FOB followed by motor activity testing on the day of 

scheduled sacrifice. 
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Two high-dose males were sacrificed moribund, one each on study day 18 and 42. Clinical signs in these 

animals included rales, salivation, urine staining, weight loss/emaciation, ungroomed coat, dyspnea, and 

gasping; at necropsy gavage error was confirmed for one animal, but a cause of death was not determined 

for the other animal. Treatment-related clinical signs of toxicity in the 40- and 80-mg/kg/day males 

included rales in 8 and 10 animals, respectively, and excessive salivation in 5 and 8 animals, respectively. 

Among female rats, clinical signs of toxicity included excessive salivation in 1 and 2 animals, 

respectively during premating, in 1 and 4 animals, respectively, during gestation, and in 0 and 1 animal, 

respectively, during lactation. 

Body weight, body weight gain, and food consumption by the 5- and 20-mg/kg/day groups was similar to 

the control group levels throughout the study. Body weight gain was slightly or significantly less than that 

of controls for the 40-mg/kg/day males beginning on the third week of the study and for the 80-mg/kg/day 

males from the beginning of the study. Mean weekly body weight gains for the 40- and 80-mg/kg/day 

males were 5-87% and 35-71%, respectively, of the control group level resulting in an overall weight 

gain for the study 65% and 20%, respectively, of the control level. The high-dose group showed a mean 

weight loss for the day 36-43 and 43- 46 intervals. Final body weight of the 40- and 80-mg/kg/day males 

was 92 and 81% of the control value. Food consumption by the 40-mg/kg/day males was significantly 

less than that of the control group during days 36-43 (p 0.05; 87% of control). Food consumption by the 

80- mg/kg/day males was significantly less than that of the controls during days 29-36, 36-43, and overall 

(p 0.05 or 0.01; 69-85% of controls). 

For females during premating, body weight, weight gain, and food consumption were similar between the 

treated and control groups. Body weight and weight gain were not affected during gestation. Food 

consumption by the high-dose females during gestation was significantly less than that of controls for 

GDs 0-12 and overall (p 0.05 or 0.01; 83-85% of control level). During lactation, body weight of the 

high-dose group was significantly less than that of controls on days 3 and 4 (p 0.05; 90% of control level). 

Body weight changes during lactation were highly variable for all treated and control groups. Food 

consumption by the high-dose group during lactation days 1-4 was 79% of the control level but did not 

attain statistical significance. 

During the functional observational battery (FOB), no treatment-related changes in home cage, handling, 

or open field behavior were observed. Sensory reactions, grip strengths, air righting response, and landing 

foot splay were similar between the treated and control groups for males and females. High-dose males 

had markedly reduced number of movements and time spent in movement (overall 50% and 42%, 

respectively, of control levels). In general, both parameters were reduced after the first 20 minutes and for 

the remainder of the session. Statistical significance was not attained due to large variability in the data. 

No differences between treated and control females were seen for motor activity. 

No biologically important differences were observed in the male or female rats at doses up to 80 

mg/kg/day in the hematology or clinical chemistry parameters. At necropsy, terminal body weight and 

absolute and relative (to brain) liver, kidney, and heart weights were significantly (pO.O5 or 0.01) 

reduced in the 80-mg/kg/day males. High-dose males also had significantly reduced organ weightrelative-to-body weight of the testes, brain, and adrenals, although the absolute weight of these organs 

was similar to the control group value. No clear effects on organ weight were seen in female rats. No 

treatment-related gross lesions were observed in male or female rats at terminal sacrifice. 

Microscopically, a dose-related increase in the incidence and severity of erosions, 

hyperplasia/hyperkeratosis, and necrosis was observed in the stomach of males and females administered 

20 mg/kg/day and higher. Thymic atrophy was found in 80-mg/kg/day males and females and in the 20-

and 40-mg/kg/day females. Dose-related increases in the incidence and severity of macrophage 
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infiltration occurred in the ileum of males at the two highest doses, in the jejunum of males at >20 

mg/kg/day and in females at 40 and 80 mg/kg/day, in the liver of high- dose males and females, and in the 

mesenteric lymph node of males at >20 mg/kg/day and in females at 40 and 80 mg/kg/day. In the lymph 

node and liver of affected animals, the macrophages coalesced to form microgranulomas. 

Estrous cycling was similar between the treated and control groups. The mean number of cycles for all 

groups was 2.4-2.8 during the premating interval. Reproduction and fertility were not affected by 

treatment. The mean duration of gestation and the mean number of implantation sites and corpora lutea 

were similar between the treated and control groups. 

Litter size and mean number of pups at first litter check and the sex ratio were not affected by treatment. 

Pup survival was similar between the treated and control groups. No treatment- related clinical signs of 

toxicity were observed in the pups during lactation. Offspring body weight for the 40 and 80 mg/kg/day 

groups was significantly less than that of the controls on lactation days 1 and 4. Body weight gain was 

markedly decreased at 80 mg/kg/day for lactation days 1-4 (1.8 g vs 3.0 g for controls). No treatmentrelated findings were noted on macroscopic examination of the pups. 

The parental /systemic LOAEL for amines, coco alkyl in rats is 20 mg/kg/day based on 

microscopic lesions in the stomach, jejunum, thymus, and lymph node in males and 

females. The parental/ systemic NOAEL is 5 mg/kg/day. 

The reproductive/developmental LOAEL for Amines, coco alkyl in rats is 40 mg/kg/day, 

based on decreased body weight and body weight gain in male and female offspring. The 

reproductive/developmental NOAEL is 20 mg/kg/day. 

This study is classified Acceptable/Guideline and satisfies the guideline requirement for a Combined 

Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test 

(OECD 422) in the rat (OPPTS 870.3650). 

CHRONIC TOXICITY

The registrant submitted no data on the chronic toxicity of the active ingredient under 

consideration (N-(coco alkyl) trimethylenediamine [also referred to as N-coco 1,3-

diaminopropane]). Instead, the registrant cited three chronic toxicity studies performed with 

octadecylamine (stearamine). The studies cited by the registrant are summaries within the 2008 

European Union Risk Assessment document. The structure of the chemical and summaries of 

these studies (all that was provided) are shown below. 

Structure:

Chronic Toxicity Study Summaries

One chronic study involved the administration of stearic acid, a metabolite of hydrogenated 

tallow alkylamines at a single dose of approximately 200 mg/kg/day for 206 days in the diet. 

Another group was fed with diet containing octadecylamine that was dissolved in corn oil (CAS 

124-30-1), while a control group was not carried along. Food consumption and the weekly 

change of body weights were recorded. Gross and microscopic examinations were made on 

major tissues (20 organs/tissues).
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Two out of five female rats died spontaneously (no details were provided). Average weight gain 

was 12 g in males and 58 g in females, and the animals were reported to be anorexic. Tissues 

from rats fed with stearic acid showed severe pulmonary infection consisting of 

tracheobronchitis, lobular pneumonia, lipoid histiocytic response, and abscess formation. No 

histomorphologic abnormalities were observed in the other organs. The authors concluded 

anorexia and increased mortalities as being substance-related toxic effects of stearic acid. This 

study used one dose and is therefore limited in its hazard characterization.

In a second study, four groups of 24 rats (12/sex) were fed diets containing 20, 100, 200, and 500 

ppm stearamine for two years (mean dose was about 1.05, 5.79, 10.68, and 27.15 mg/kg/day for 

350 g males and 1.20, 5.80, 10.08, and 28.20 mg/kg/day for 250 g females). Feed consumption, 

growth rate, death rate, and blood cell counts for the experimental animals were comparable to 

those of the control animals. Tissues examined by histopathology examination included brain, 

viscera, gonads, skeletal muscle, bone marrow, heart, lungs, liver, spleen, kidneys, gastroenteric 

tract (3 levels), pancreas and lymph nodes. The organs examined microscopically included the 

heart, lungs, liver, spleen, kidneys, gastrointestinal tract (3 levels), pancreas, lymph nodes, bone 

marrow, brain, pituitary, adrenals, and ovary or testis. The feed consumption, growth rate, death 

rate, and blood cell counts for the experimental animals were comparable to those of the control 

animals. One rat receiving 500 ppm showed histiocytic hyperplasia of the mesenteric lymph 

node. At necropsy, no significant differences were found between the experimental and control 

groups in the incidence and types of lesions observed. Having the histiocytic accumulations at 

3000 ppm (seen in the 209 day-study in rats) and lesions of the same nature in the dog in mind, 

the single case of histiocytic hyperplasia in the mesenteric lymph node of the single rat treated 

with 500 ppm (25 mg/kg/day) for 2 years (in this study) could also be interpreted as a treatmentrelated. Therefore a NOAEL of 200 ppm (10 mg/kg/day) is proposed for the 2-year rat 

studies. 

In a third study, three groups of three dogs (2 females and 1 male or 2 males and 1 female) each 

were fed 0.6, 3.0, and 15.0 mg/kg/day octadecylamine ("stearamine") in corn-oil solution that 

was administered by capsule once daily (5 d/wk) A control group of dogs was given untreated 

feed. Dogs were housed in individual cages and fed once daily. Hematological examinations 

consisted of total red blood cell count, hemoglobin concentration, total and differential white cell 

counts and were performed on all dogs at the start of the experiment and at 1, 2, 3, 6, 8, 11, and 

12 months thereafter. The organs examined microscopically included the heart, lungs, liver, 

spleen, kidneys, gastroenteric tract (3 levels), pancreas, lymph nodes, bone marrow, brain, 

pituitary, adrenals, and ovary or testis. The high dose group gained less weight than the control 

and lower-dose animals. The weight gain for the two lower-dose groups was similar to that of the 

controls. Blood cell counts were comparable in experimental and control animals. Only one dog 

died before study termination (after week 22); this dog was from the group receiving 15.0 mg/kg 

bw/d octadecylamine and suffered from anorexia, bloody diarrhea and what appeared to be 

gastroenteric irritation. At necropsy, two animals from the high-dose group had lesions 

suggestive of the mesenteric lymph nodes, which were filled with pale histiocytes. Also, pale 

staining of the tips of the villi of the small intestine mucosa was observed in these dogs. 

However, no definite lesions were identified in the intestinal tracts of these animals or in any of 

the other experimental animals. [No other information available.] Considering the mortality 
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associated with anorexia and hemorrhagic diarrhea in one dog, growth depression in two other 

dogs, and the lymph node histiocytosis observed at 15 mg/kg bw/d as a treatment-related toxic 

effect, the NOAEL in dogs fed with octadecylamine (CAS 124-30-1) for 1 year was 3 

mg/kg/day.

CARCINOGENICITY

The registrant did not submit any carcinogenicity data for the active ingredient N-(coco-alkyl)

trimethylenediamine, but instead cited a study in the 2008 European Union risk assessment 

conducted on octadecylamine. The summary of that study is shown below, as printed in the 2008 

European Union risk assessment.

“A 2-year toxicity study of octadecylamine ("stearamine") was conducted using SpragueDawley rats. Four groups of 24 rats (12/sex) were fed diets containing 20, 100, 200 and 500 ppm 

stearamine (reviewed by Pang, 1995, original data University of Miami, 1957, Deichmann et al., 

1958). A control group of animals was fed the base diet alone. The feed consumption, growth 

rate, death rate, and blood cell counts for the experimental animals were comparable to those of 

the control animals. The survival rate for this study was 17-33% including the control group. At 

necropsy, no significant differences were found between the experimental and control groups in 

the incidence and types of lesions observed. No significant increase occurred in the incidence of 

lesions. [No other information available.]”

While this summary provides little information on carcinogenicity, there are additional pieces of 

information that would support the lack of carcinogenic potential for these chemicals. The first 

piece of information is the mutagenicity database for the alkyl amine compounds assessed in the 

2008 European Union risk assessment, where the data show these chemicals to be negative for 

mutagenicity in a variety of assays. The second piece of information available is a structureactivity analysis conducted by OPP’s Health Effects Division as part of the 2009 risk assessment 

for linear alkyl amines as inerts in pesticide formulations. Using the DEREK software program 

for prediction of structural alerts that may indicate concern for carcinogenicity, there were no 

identified structural alerts of concern for the chemicals screened. The third piece of information 

available are mutagenicity data cited in the alkyl trimethylenediame RED that also showed 

negative results for mutagenicity. 

The fourth piece of information is an analysis conducted for the N-alkyl amines and the alkyl 

diamines (collectively known as aliphatic amines) using the Oncologic SAR program. This 

analysis was conducted by the Office of Pollution Prevention and Toxics, one of the major 

program offices within the Office of Chemical Safety and Pollution Prevention. Their analysis 

states in part, ”unlike aromatic amines, aliphatic amines are generally not considered to have 

significant carcinogenic activity unless the alkyl group is small and contains reactive groups 

(e.g., terminal Cl/Br/I) or pro-reactive groups (e.g., unhindered terminal double bond). Although 

hydroxylamines of aliphatic amines can be reactive, they are usually too short-lived to have 

effects beyond local action.” 
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Toxicology References

MRID 47646101 . Lech, J.W. (2008): Oral (Gavage) Combined Repeated Dose Toxicity Study 

with a Reproduction/Developmental Toxicity Screening Test of Amines, coco alkyl 

(CAS# 61788-46-3). Charles River Laboratories Preclinical Services Protocol Number

WOB00004. 

MRID49092802 Takawale, P. (2010) 90-Day Repeated Dose Oral Toxicity Study with 28-

Day and 90-Day Recovery Period in Rats with N-C12,14 Alkyl-1,3-

diaminepropane for [N-(coco alkyl)trimethylenediamine]: Final Report. 

Project Number: 081580/OCR. Unpublished.

European Union Risk Assessment Report (2008): Primary Alkyl Amines Risk Assessment. 
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Appendix B Environmental Fate

Environmental Fate and Transport Properties of ATMD 

Compounds

Environmental Fate Assessment

The alkyl trimethylenediamines are used primarily as microbiocides, bactericides, or 

molluscicides in industrial cooling towers (recirculating and once-through) and for oilfield uses. 

As a group, ATMD chemicals are not susceptible to degradation by abiotic processes (hydrolysis 

and photodegradation in water).

10 No useable data have been submitted to demonstrate potential

biotic degradation for all ATMD chemicals. 

The only ATMD chemical for which environmental fate data have been submitted is N-

(cocoalkyl) trimethylenediamine (PC code 067301). These environmental fate data demonstrate 

that it is strongly sorbed to soil, sediment, and sludge and it is not readily biodegradable in 

wastewater treatment plants (WWTPs).11 As a result, Table B1 only contains information on 

067301. 

ATMD chemicals are not likely to degrade by abiotic processes (hydrolysis and 

photodegradation in water) and the extent of biological degradation is unknown for all of the 

ATMD chemicals because of the lack of data. The only ATMD chemical with data on sorption to 

soil or sediment is N-(cocoalkyl) trimethylenediamine (PC code 067301), which has been 

demonstrated to be tightly sorbed. Based on a bioconcentration study, there is limited 

bioconcentration of N-(cocoalkyl) trimethylenediamine in fish. The agency anticipates requiring 

aerobic and anaerobic aquatic metabolism (835.4300 and 835.4400) for all PC codes and soil and 

sediment absorption/desorption isotherm data (835.1230) for the three miscible compounds (PC 

codes 067302, 067310, and 067313), allowing data generated on any one of the three to satisfy 

the requirement. In addition, the agency is requiring environmental fate data for the three 

miscible compounds for all the other fate data requirements in Table 6 because data have not 

been submitted. 

The only ATMD chemical for which activated sludge respiration inhibition (OCSPP 850.3300) 

data have been submitted is N-coco-1,3-diaminopropane (PC code 067301) with an IC50 of 21.9

mg/l (>20) (MRID 49040218). Since the ASRI test previously submitted to the agency for 

067301 provided only supplemental information (MRID 49040218), the agency is also requiring 

additional ASRI testing for all PC codes because the 95 % confidence intervals were too wide. In 

addition, the agency anticipates requiring an Activated Sludge Respiration Inhibition (ASRI) test 

for PC codes 067302, 067310, and 067313 to help determine the type of wastewater treatment 

plant biodegradability test that will be required and to determine toxicity to activated sludge 

microorganisms.

 

10 Appendix B

11 MRIDs 49040206, 49040205, 49040207
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Based on the vapor pressure and Henry’s Law values in Table 3, none of the ATMD chemicals

are expected to move into the air in significant quantities from the registered use sites.

Water and Sediment

Hydrolysis

The only chemical for which hydrolysis data (OCSPP 835.2120) are available is N-(coco alkyl) 

trimethylenediamine (PC code 067301). It was stable to hydrolysis at pH 5, 7, and 9 (MRIDs 

40062413 and 41069001). Based on the chemical structure of all ATMD chemicals in this case 

(3014), none are expected to be likely to degrade by hydrolysis and no additional hydrolysis data 

are anticipated to be required.

Aqueous Photolysis

Data on photodegradation in water (OCSPP 835.2240) have not been submitted for any of the 

ATMD chemicals but none are expected to photodegrade directly based on their chemical 

structure. Therefore, photodegradation in water data are not anticipated to be required.

Octanol-Water Partition Coefficient and Bioconcentration in Fish

The log P (log Kow) for ATMD chemicals can vary with the length of the alkyl chain, which 

includes 8 to 18 carbons (C8-C18). For all ATMD chemicals in this case except 067301, the log P 

is not applicable because these are polar chemicals. However, for PC code 067301, the log P is 

0.2 which represents a weighted average of the percent alkyl chain length. The log P ranged 

from -3 (C8) to 2.5 (C18) (MRID 49040203). 

Based on this average log P, there is limited bioconcentration of N-(cocoalkyl) 

trimethylenediamine in fish with BCF values of 180-525X (MRID 49040210). 

Aerobic Aquatic Metabolism

Data on aerobic aquatic metabolism (OCSPP 835.4300) have not been submitted and are 

anticipated to be required for all PC codes. For the miscible compounds (PC codes 067302, 

067310, and 067313), the agency anticipates allowing data generated on any of these PC codes 

to satisfy the requirement.

Anaerobic Aquatic Metabolism

Data on anaerobic aquatic metabolism (OCSPP 835.4400) have not been submitted and are 

anticipated to be required for all PC codes. For the miscible compounds (PC codes 067302, 

067310, and 067313), the agency anticipates allowing data generated on any of these PC codes 

to satisfy the requirement.
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Soil

Soil Leaching/Adsorption/Desorption Batch Equilibrium

Data on leaching-adsorption-desorption were not submitted for any of the ATMD chemicals 

except for N-coco-1,3-diaminopropane (PC code 067301). The Freundlich Kads values ranged 

from 14,454-50,898 ml/g and the Koc values ranged from 696,677-1,211,857 ml/g (5 soils). The 

fit of the Freudlich equation was good with R2values of 0.88-0.97 (Table B1 below). Sorption 

was most closely related to the cation exchange capacity (CEC) of the soils (r2=0.55), which 

represents the combination of clay and organic carbon content and pH. Based on the Koc values 

in tested soils and the FAO classification,12 parent n-coco-1,3-diaminopropane is immobile in 

soil (MRID 49040206).

Data on sorption to soil and sediments are anticipated to be required for PC codes 067302, 

067310, and 067313.

Aerobic Soil Metabolism

Data on aerobic soil metabolism (OCSPP 835.4100) have not been submitted for these ATMD 

chemicals and are not anticipated to be required because the use patterns are not expected to lead 

to significant releases to the soil environment.

Anaerobic Soil Metabolism

Data on anaerobic soil metabolism (OCSPP 835.4200) have not been submitted for these ATMD 

chemicals and are not anticipated to be required because the use patterns are not expected to lead 

to significant releases to the soil environment.

Fate and Transport in WWTP

Activated Sludge Sorption Isotherm

The only ATMD chemical for which acceptable activated sludge sorption isotherm data (OCSPP 

835.1110) have been submitted is N-coco-1,3-diaminopropane (PC code 067301). It had a Kf 

value of 39,753 and a Koc value of 105,222 L/kg (MRID 49040205). The results from the 

Activated Sludge Sorption Isotherm (ASSI) test demonstrated that an average of 83 % sorption 

to activated sludge occurred within 4-6 hours, which is a period that typifies average residence 

time in an activated sludge basin. In the absence of other data that would indicate degradation 

and/or transport of 067301, the agency assumed an overall removal of 83 % during wastewater 

treatment in assessing risk for use of 067301 in cooling water systems. 

 

 

12 FAO classification system, http://www.fao.org/docrep/003/x2570e/x2570e06.htm
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Activated Sludge Biodegradation

The only ATMD chemical for which biodegradability in wastewater treatment plant data have 

been submitted is N-coco-1,3-diaminopropane (PC code 067301). To fulfill the data requirement 

for biodegradability in a wastewater treatment plant, the registrant submitted a ready 

biodegradability study (MRID 49040207). This study, however, did not meet the criteria for 

ready biodegradability. Consequently, based on the results of this study, the agency could not 

consider removal via biodegradation during wastewater treatment as part of the overall removal 

used as an input to the E-FAST down-the-drain module. Even though PC code 067301 did not 

demonstrate the potential to readily biodegrade, the results from the Activated Sludge Sorption 

Isotherm (ASSI) test demonstrated that an average of 83 % sorption to activated sludge occurred 

within 4-6 hours (MRID 49040205), which is a period that typifies average residence time in an 

activated sludge basin. In the absence of other data that would indicate degradation and/or 

transport of 067301, the agency assumed an overall removal of 83 % during wastewater 

treatment in assessing risk for use of 067301 in cooling water systems. For the agency to 

consider removal via biodegradation during wastewater treatment, data from a WWTP 

biodegradation simulation test is required. 

Wastewater treatment plant biodegradability data on PC codes 067302, 067310, and 067313 are

anticipated to be required. The outcome of the ASRI test will determine whether a ready 

biodegradability test or a simulation test will be required.

Activated Sludge Respiration Inhibition

The only ATMD chemical for which activated sludge respiration inhibition (OCSPP 850.3300) 

data have been submitted is N-coco-1,3-diaminopropane (PC code 067301) with an IC50 of 21.9 

mg/l (>20) (MRID 49040218). MRID 49040218 was considered to contain supplemental data 

only because the confidence bounds on the IC50 value of 22 mg/l (10-30 mg/l) are too wide, 

based on the fact that an IC50 of 20 mg/l is the trigger for requiring or not requiring 

biodegradation simulation studies rather than a ready biodegradability study. As a result, it 

cannot be concluded with reasonable confidence that the activated sludge IC50 is 22 mg/L. 

Consequently, ASRI data are still anticipated to be required for all PC codes. For the miscible 

compounds (PC codes 067302, 067310, and 067313), the agency anticipates allowing data 

generated on any of these PC codes to satisfy the requirement. 
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Table B1. Environmental Fate Properties for PC Code 067301

Property OCSPP Guideline 

No. (unless stated)

Value Citation

Hydrolysis 835.2120 Stable at pH 5, 7, and 9 40062413

41069001

93034010

Photodegradation 

in water 

835.2240 Not required13 None

Photodegradation 

on soil

835.2410 Not required14 None

Aerobic soil 

metabolism

835.4100 No data None

Anaerobic soil 

metabolism

835.4200 No data None

Aerobic aquatic 

metabolism 

835.4300 No data15 49208802

Anaerobic 

aquatic 

metabolism

835.4400 No data16 49208803

Leachingadsorptiondesorption835.1230 Kads and Koc values ranged 

from 5,760-32,600 and 

446,684-1,000,000

49040206

Bioconcentration 

in fish

850.1730 BCF values of 180-205X

50 % depuration by 17 days 

49040210

Activated sludge 

sorption isotherm

(L/kg)

835.1110 Kf and Koc of 39,753 and 

105,222

49040205

Ready 

biodegradability 

(%)

835.3110 Not readily biodegradable 49040207

Activated sludge 

respiration 

inhibition (mg/L).

850.3300 21.9 49040218

 

13 Waived based on lack of UV sorption above 290 nm

14 Not expected to be required based on lack of UV sorption from 290-800 nm

15 MRID 49208802 was reviewed and found to have no data which could be used for EPA’s exposure assessment.

16 MRID 49208803 was reviewed and found to have no data which could be used for EPA’s exposure assessment.
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Environmental Fate References

MRID 40062413. Bisinger, Jr., E.C. Hydrolysis Study: Environmental Fate Data Requirements. 

Unpublished study performed and submitted by Akzo Chemie America, Chicago IL. 

MRID 41069001. Bisinger, Jr., E. C. April 14, 1989. Hydrolysis of Duomeen-C Acetate: 

Environmental Fate Data Requirements. Unpublished study performed and submitted by Akzo 

Chemicals, Chicago, IL. 

MRID 49040205. Schaefer, E.; Ponizovsky, A. (2012) [N-(coco alkyl)trimethylenediamine]: 

Activated Sludge Sorption Isotherm. Project Number: 709E/103/OCR. Unpublished study 

prepared by Wildlife International, Ltd. 65p.

MRID 49040206. Schaefer, E.C. and Ponizovsky, A.A., 2012b. [N-(coco 

alkyl)trimethylenediamine]: Adsorption/Desorption Characteristics In Five Representative Soils. 

Project ID 709E-102, Wildlife International, Ltd., Performed on behalf of Mexel Industries, 

SAS. 124 pp.

MRID 49040207. van Ginkel, C.G. May 23, 2012. Biodegradability of n-coco-1,3-diaminodiamineopropane (CAS 61791-63-7) in the closed bottle test (OECD TG 301 D). Unpublished 

study by Akzo Nobel Arnhem, study number: T12018C.

MRID 49040210. Thomas, S.T., Kendall, T.Z., and Gallagher, S.P., 2013. [N-(coco 

alkyl)trimethylenediamine]: A flow-through bioconcentration test with the bluegill (Lepomis 

macrochirus). Project ID 709A-110, Wildlife International, Ltd., Performed on behalf of Mexel 

Industries, SAS. 115 pp.

MRID 49040218. Schaefer, E.C. and Twilley, B.C., 2011. [N-(coco alkyl)trimethylenediamine]: 

An activated sludge, respiration inhibition test. Project ID 709E-1 01, performed on behalf of 

Mexel Industries, SAS.

US EPA, 2012b. Estimation Programs Interface SuiteTM for Microsoft® Windows, v 4.11. 

United States Environmental Protection Agency, Washington, DC, USA. 

http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

US EPA, February 10, 2014. Risk Assessment for the Proposed Registration of the New Use of 

ATMD to Control Bio-fouling in Once-Through Cooling Systems and Recirculating Cooling 

Towers. D415622, D415970, D411969, D416478.
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Appendix C Ecotoxicology Profile

The available ecotoxicity data are tabulated below for each receptor group. Data are bridged 

among the PC codes for all receptor groups except sediment-dwelling invertebrates. PC code 

067301 is the only ATMD expected to bind to soil and aquatic sediments; therefore, sediment 

toxicity data are anticipated to be needed for that PC code.

Toxicity to Terrestrial Organisms

Birds

Two acceptable and three supplemental acute-oral studies categorize the AMTDs as being 

practically nontoxic to very highly toxic to birds. The guideline (850.2100) is satisfied. 

Avian Acute-oral Toxicity

Test Species Test Material

(% ai)

LD50

(mg ai/kg bw)

Toxicity

Category

EPA Study

ID

Northern bobwhite

(Colinus virginianus)

100 0.24 Very highly toxic 470013023 

Acceptable

Not reported 492 Moderately toxic 97534

Acceptable

23.5 500 Moderately toxic 106859

Supplemental

22 681 Slightly toxic 134550

Supplemental

Mallard 

(Anas platyrhynchos) 22 3200 Practically nontoxic 110384

Supplemental

Eight available dietary (LC50) studies categorize the AMTDs as being practically nontoxic to 

slightly toxic birds when administered in the diet. No additional data are anticipated as being

needed for this guideline (850.2200). 

Avian Dietary Toxicity

Test Species Test Material

(% ai)

LC50

(ppm)

Toxicity

Category

EPA Study

ID

Northern bobwhite

(Colinus virginianus)

100 6400 Practically nontoxic 470013024 

Acceptable

32 6400 Practically nontoxic 40062405

Acceptable
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0.03 >10,000 Practically nontoxic 123864 Acceptable

Not reported 5000 Practically nontoxic 97535 Supplemental

Mallard

(Anas platyrhynchos)

50 5000 Slightly nontoxic 133266 Acceptable

0.03 100,000 Practically nontoxic 123863 Acceptable

32 6400 Practically nontoxic 470013025

Supplemental

Not reported 5000 Practically nontoxic 97516 

Supplemental

Nontarget Insects 

Toxicity data for beneficial insects (850.3020, 850.3030) are anticipated to be required only for 

pesticides with wood preservative uses. Because the ATMDs have no wood preservative uses, 

data are not anticipated to be required. 

Toxicity to Aquatic Organisms

Freshwater Fish 

The available acute toxicity studies categorize the AMTDs as being slightly to highly toxic to 

freshwater fish. The guideline (850.1075) for acute toxicity testing is satisfied. 

Freshwater Fish Acute Toxicity

Test Species Test Material

(% ai)

96-h LC50

(mg ai/L)

Toxicity

Category

EPA Study

ID

Rainbow Trout

(Oncorhynchus mykiss) 32 0.12 Highly toxic 41786606Acceptable

0.03 1300 Slightly toxic 123862

Acceptable

Not reported 1.58 Moderately toxic 97518

Supplemental

Bluegill

(Lepomis macrochirus)

50 0.03 Highly toxic 133265

Acceptable

32 0.96 Highly toxic

41786601

Acceptable

32 0.03 Highly toxic 41786601

Supplemental
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0.03 1390 Practically nontoxic 123862

Acceptable

Chronic data are available for the fathead minnow. Based on the ACR for the fathead minnow 

(acute toxicity predicted from Web-ICE) and the acute toxicity value for the rainbow trout, an 

NOAEC value of 4.02 μg ai/L was determined for the rainbow trout. No additional chronic data 

are anticipated to be needed (fish early-life stage, 850.1400).

Freshwater Fish Chronic Toxicity

Test Species Test Material

(% ai)

NOAEC

(mg ai/L)

LOAEC

(mg ai/L)

EPA Study

ID

Fathead minnow

(Pimephales promelas)

94.1 0.011 0.023 49040209

Acceptable

Rainbow Trout

(Oncorhynchus mykiss)

NA 0.004* nd 49208804

Acceptable

* determined from ACR for fathead minnow

Freshwater Invertebrates

The four available acute toxicity studies for the waterflea categorize the AMTDs as being highly 

to very highly toxic to freshwater invertebrates. One chronic study found no adverse effects on 

daphnid reproduction or growth at concentrations up to 0.054 mg ai/L. The guidelines for acute 

(850.1010) and chronic (850.1300) toxicity testing are satisfied. 

Freshwater Invertebrate Acute and Chronic Toxicity

Test Species Test Material

(% ai)

Toxicity Endpoint

(mg ai/L)

Toxicity

Category

EPA Study

ID

Waterflea

(Daphnia magna)

Acute:

32 48-h EC50 = 0.051 Very highly toxic

41786602

Acceptable

32 48-h EC50 = 0.16 Highly toxic 41786602

Acceptable

32 48-h EC50 = 0.104 Highly toxic 40062409

Acceptable

Not reported 48-h EC50 = 0.12 Highly toxic 97521

Supplemental

Chronic:

94.1 NOAEC = 0.016

LOAEC = 0.054 NA 49040208Acceptable
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Estuarine/Marine Fish and Invertebrates 

The available studies categorize the AMTDs as being highly to very highly toxic to fish and 

practically nontoxic to very highly toxic to invertebrates. The guidelines for acute toxicity

(850.1075, 850.1035, and 850.1025/1055) are satisfied. Chronic toxicity testing (850.1300) is not 

anticipated to be needed. 

Estuarine/Marine Acute Toxicity

Test Species Test Material

(% ai)

Toxicity Endpoint

(mg ai/L)

Toxicity

Category

EPA Study

ID

Atlantic silverside

(Menidia menidia) 

32 96-h EC50 = 0.155 Highly toxic

41786604

Acceptable

32 48-h EC50 = 0.577 Highly toxic 41786604

Acceptable

Mysid shrimp 

(Mysidopsis bahia) 32 96-h EC50 = 0.019 Very highly toxic 41786605

Acceptable

Quahog clam 

(Mercenaria 

mercenaria) 

32 48-h EC50 = 0.019 Very highly toxic 41786603

Acceptable

White shrimp 

(Penaeus setiferus) 32 96-h EC50 = 2.39 Moderately toxic 40062411

Supplemental

Eastern oyster 

(Crassostrea virginica)

32 96-h EC50 = 720 Practically nontoxic 40062412

Acceptable

Pink shrimp 

(Penaeus duorarum) 0.03 96-h EC50 = 1000 Practically nontoxic 123866

Acceptable

Fiddler crab 

(Uca pugilator) 0.03 96-h EC50 = 1000 Practically nontoxic 123866

Acceptable

Blue crab 

(Callinectes 

trimethylenedi) 

Not reported 96-h EC50 = 387 Practically nontoxic 97520

Supplemental

Aquatic Plants 

Studies available for the TGAI include a toxicity test with duckweed, a vascular species 

(850.4400), and algal toxicity tests (850.4500) with green algae (2 spp.), a freshwater diatom, 

and a marine diatom. Data for cyanobacteria are not available. In the absence of an ecotoxicity 

study for cyanobacteria, Web-ICE17 was previously used to predict an EC50 = 0.012 mg ai/L. 

However, that prediction does not satisfy the guideline (850.4550). A study with cyanobacteria is 

anticipated as being needed. 

 

17 Web-ICE (EPA 2013); http://www.epa.gov/ceampubl/fchain/webice/
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Aquatic Plant Toxicity

Test Species Test Material

(% ai)

Toxicity Endpoints

(mg ai/L)

EPA Study

ID

Duckweed

(Lemna gibba)

94.1 7-d EC50 = 0.123

NOAEC = 0.020

49040213

Acceptable

Green algae

(Pseudokirchneriella subcapitata) 94.1 96-h EC50 = 0.0052

NOAEC = 0.0024

49040216

Acceptable

Green algae

(Scenedesmus subspicatus) 94.1 96-h EC50 = 0.011

NOAEC = 0.0069 

49040217

Acceptable

Freshwater diatom

(Navicula pelliculosa) 94.1 96-h EC50 = 0.017

NOAEC = 0.009 

49040215

Acceptable

Marine Diatom 

(Skeletonema costatum) 94.1 96-h EC50 = 0.011

NOAEC = 0.008

49040214

Acceptable

Cyanobacteria

(Anabaena flos-aquae)

-- Data gap --

Subchronic Invertebrate Sediment Toxicity

Two subchronic studies are available for PC code 067301, which is the only ATMD expected to 

bind to aquatic sediments. For the freshwater environment, two species are required, and a study 

with a freshwater amphipod (850.1735) is anticipated to be needed for 067301 since it is the only 

compound expected to be found in sediments. Data are not required for the other three 

compounds which are expected to remain in the water column. No additional data are anticipated 

as being needed for freshwater midge (850.1735) or estuarine/marine amphipod (850.1740).

Subchronic Invertebrate Sediment Toxicity for PC Code 067301

Test Species Test Material

(% ai)

Toxicity Endpoints

(mg ai/kg sediment)

EPA Study

ID

Freshwater Midge 

(Chironomus tentans)

94.1 10-d EC50 = 188

NOAEC = 16 

49040211

Acceptable

Freshwater amphipod TGAI Data gap --

Marine Amphipod 

(Leptocheirus plumulosus)

94.1 10-d EC50 = 303

NOAEC = 174 

49040212

Acceptable

Ecotoxicity References 

MRID 41786602 Surprenant, D. 1988. Acute Toxicity of Microbiocide 56 to Daphnids (Daphnia 

magna): Lab Project Number: 88-3-2669: 384.1187.6100.110. Unpublished study prepared by Springborn 

Life Sciences, Inc. 20p. 
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MRID 41786603 . Surprenant, D. 1988. Acute Toxicity of Microbiocide 56 to Embryo-Larvae of the 

Quahog Clam (Mercenaria mercenaria) Under Static Renewal Conditions: Lab Project Number: 88-5-

2712. Unpublished study prepared by Springborn Life Sciences, Inc. 20p. 

MRID 41786604 Surprenant, D. 1988. Acute Toxicity of Microbiocide 56 to Silversides (Menidia 

menidia) Under Static Renewal Conditions: Lab Project Number: 88-4-2687: 384.1187.6100.501. 

Unpublished study prepared by Springborn Life Sciences, Inc. 19p. 

MRID 41786605.Surprenant, D. 1988. Acute Toxicity of Microbiocide 56 to Mysid Shrimp 

(Mysidopsis bahia): Lab Project Number: 88-4-2739: 384.1187.6100.510. Unpublished study 

prepared by Springborn Life Sciences, Inc. 20p. 

MRID 41786606 Surprenant, D. 1990. Acute Toxicity of Microbiocide 56 to Rainbow Trout 

(Salmo gairdneri) Under Static Conditions: Lab Project Number: 88-11-2861: 384.0788.6101.103. 

Unpublished study prepared by Springborn Life Sciences, Inc. 19p. 

MRID 40062404. Bisinger, E. (1984) Avian Oral LD50 in Bobwhite Quail: Wildlife and Aquatic 

Organism Data Requirements: Armohib B-101: Report No. T-4000: [Supplemental Data Submitted in 

Response to EPA’s Comments]. Unpublished study prepared by Akzo Chemie America and Product 

Safety Labs. 14p.

MRID 40062405. Bisinger, E. (1984) Avian Dietary LC50 in Bobwhite Quail: Wildlife and Aquatic 

Organism Data Requirements: Armohib B-101: Report No. T-3995: [Supplemental Data Submitted in 

Response to EPA’s Comments]. Unpublished study prepared by Akzo Chemie America and Product 

Safety Labs. 13p.

MRID 40062609. Bisinger, E. (1984) Acute LC50: Daphnia magna: Wildlife and Aquatic Organism 

Data Requirements: Armohib B-101: Report No. H-8241: [Supplemental Data Submitted in Response to 

EPA’s Comments]. Unpublished study prepared by Akzo Chemie America and MBA Laboratories. 14p.

MRID 40062411. Bisinger, E. (1984) Acute LC50 in Estuarine and Marine Organisms/96-hour LC50 in 

White Shrimp: Wildlife and Aquatic Organism Data Requirements: Armohib B-101: Report No. H-8241: 

[Supplemental Data Submitted in Response to EPA’s Comments]. Unpublished study prepared by Akzo 

Chemie America and MBA Laboratories. 14p.

MRID 40062412. Bisinger, E. (1984) Acute LC50 in Estuarine and Marine Organisms/96-hour LC50 in 

Oyster: Wildlife and Aquatic Organism Data Requirements: Armohib B-101: Report No. H-8241: 

[Supplemental Data Submitted in Response to EPA’s Comments]. Unpublished study prepared by Akzo 

Chemie America and MBA Laboratories. 14p.

MRID 49040208 Minderhout, T. et al. 2012. [N-(COCO ALKYL)TRIMETHYLENEDIAMINE]: A 

Flow-through Life-cycle Toxicity Test with the Cladoceran (Daphnia magna). Wildlife International, Ltd. 

Project No.: 709A-108A. Mexel Industries, SAS: C/O Mexel USA, LLC. 

MRID 49040209 Minderhout, T., K. et al. 2012. [N-(COCO ALKYL)TRIMETHYLENEDIAMINE]: 

An Early Life-Stage Toxicity Test with the Fathead Minnow (Pimephales promelas). Wildlife 

International, Ltd. Project No.: 709A-109A. Mexel Industries, SAS: C/O Mexel USA, LLC. 
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MRID 49040211 Thomas, S. et al. 2013. [N-(COCO ALKYL)TRIMETHYLENEDIAMINE]: A 10-day 

Survival and Growth Toxicity Test with the Midge (Chironomus tentans) Using Spiked Sediment. 

Wildlife International, Ltd. Project No: 709A-106. Study sponsored by Mexel Industries, SAS C/O 

Mexel USA, LLC. 

MRID 49040212 Thomas, S. et al. 2013. [N-(COCO ALKYL)TRIMETHYLENEDIAMINE]: A 10-day 

Survival Test with the Marine Amphipod (Leptocheirus plumulosus) Using Spiked Sediment. Wildlife 

International, Ltd. Project No: 709A-107A. Study sponsored by Mexel Industries, SAS C/O Mexel USA, 

LLC. 

MRID 49040213 Jacobs, A. et al. 2012. [N-(COCO ALKYL)TRIMETHYLENEDIAMINE]: A 7-Day 

Static-Renewal Toxicity Test with Duckweed (Lemna gibba G3). Wildlife International, Ltd. Project No: 

709A-101. Study sponsored by Mexel Industries, SAS C/O Mexel USA, LLC. 

MRID 49040214 Jacobs, A. et al. 2012. [N-(COCO ALKYL)TRIMETHYLENEDIAMINE]: A 96-hour 

Toxicity Test with the Marine Diatom (Skeletonema costatum). Wildlife International, Ltd. Project No: 

709A-104. Study sponsored by Mexel Industries, SAS C/O Mexel USA, LLC. 

MRID 490402-15 Jacobs A. et al. 2012. [N-(COCO ALKYL)TRIMETHYLENEDIAMINE]: A 96-

hour Toxicity Test with the Freshwater Diatom (Navicula pelliculosa). Wildlife International, Ltd. 

Project No: 709A-105. Study sponsored by Mexel Industries, SAS C/O Mexel USA, LLC. 

MRID 49040216 Jacobs, A. et al. 2012. [N-(COCO ALKYL)TRIMETHYLENEDIAMINE]: A 96-hour 

Toxicity Test with the Freshwater Alga (Pseudokirchneriella subcapitata). Wildlife International, Ltd. 

Project No: 709A-102. Study sponsored by Mexel Industries, SAS C/O Mexel USA, LLC. 

MRID 49040217 Jacobs, A. et al.. 2012. [N-(COCO ALKYL)TRIMETHYLENEDIAMINE]: A 96-

hour Toxicity Test with the Freshwater Alga (Scenedesmus subspicatus). Wildlife International, Ltd. 

Project No: 709A-103. Study sponsored by Mexel Industries, SAS C/O Mexel USA, LLC. 

97516. Casterton, P.L. (1979) Avian Dietary LC50 (Mallard Duck): Laboratory Report No. K-5096. 

(Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and Biochemical 

Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242696-A)

97518. Reed, D. (1979) Laboratory Test Report: Static LC50: Rainbow Trout: Laboratory Report No. K5096. (Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and 

Biochemical Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242698-A)

97519. Casterton, P.L. (1979) Fish Acute LC50 (Redear Sunfish): Laboratory Report No. K-5096. 

(Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and Biochemical 

Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242699-B)

97520. Casterton, P.L. (1979) Laboratory Test Report: (Static LC50: Blue Crab): Laboratory Report No. 

K-5096. (Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and 

Biochemical Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242699-A)
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97521. Kresse, H.J. (1980) Daphnia magna: Acute LC50: Laboratory Report No. K-5096. (Unpublished 

study received Jun 16, 1980 under 38231-2; prepared by Microbiological and Biochemical Assay 

Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242698-B)

97534. Casterton, P.L. (1979) Avian Acute Oral LD50: Bobwhite Quail: Laboratory Report No. K-5096. 

(Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and Biochemical 

Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242695-A)

97535. Casterton, P.L. (1979) Avian Dietary LC50 (Bobwhite Quail): Laboratory Report No. K-5096. 

(Unpublished study received Jun 16, 1980 under 38231-2; prepared by Microbiological and Biochemical 

Assay Laboratories, submitted by C-E Natco, Tulsa, Okla.; CDL: 242695-B)

106859. Fletcher, D. (1973) Report to Nalco Chemical Company: Acute Oral Toxicity Study with 32D16 

in Bobwhite Quail: IBT No. 651-02892. Unpublished study received Apr 9, 1973 under 1706-126; 

prepared by Industrial Bio-Test Laboratories, Inc., submitted by Nalco Chemical Co., Oak Brook, IL; 

CDL: 051060-D)

110384. Fletcher, D. (1973) Report to Nalco Chemical Company: Acute Oral Toxicity Study with 32D16 

in Mallard Ducks: IBT No. 651-02893. Unpublished study received Apr 9, 1973 under 1706-126; 

prepared by Industrial Bio-Test Laboratories, Inc., submitted by Nalco Chemical Co., Oak Brook, IL; 

CDL: 051060-C)

123862. Bentley, R. (1975) Acute Toxicity of Co-op Turbex to Lepomis macrochirus and Salmo 

gairdneri. (Unpublished study received Mar 5, 1975 under 1990-372; prepared by Bionomics, EG&G 

Environmental Consultants; submitted by Farmland Industries, Inc., Kansas City, MO; CDL: 110678-A)

123863. WARF Institute, Inc. (1975) Report: WARF Institute No. 4112599. (Unpublished study received 

Mar 5, 1975 under 1990-372; submitted by Farmland Industries, Inc., Kansas City, MO; CDL: 110680-A)

123864. WARF Institute, Inc. (1975) Report: WARF Institute No. 4112599. (Unpublished study received 

Mar 5, 1975 under 1990-372; submitted by Farmland Industries, Inc., Kansas City, MO; CDL: 110680-B)

123866. Heitmuller, T. (1975) Acute Toxicity of Surflo-B15 to Larvae of the Eastern Oyster 

(Crassostrea virginica), Pink Shrimp (Penaeus duorarum), and Fiddler Crab (Uca pugilator). 

(Unpublished study received Jun 1, 1975 under 17664-11; prepared by Bionomics—EG&G, Inc., 

submitted by Baroid Div., N.L. Industries, Inc., Houston, TX; CDL: 165021-A)

133265. Thompson, C.; McAllister, W. (1983) Acute Toxicity of EH&S 266 to Bluegill Sunfish: Static 

Bioassay Report 30595. (Unpublished study received Oct 25, 1983 under 10349-14; prepared by 

Analytical Biochemistry Laboratories, Inc., submitted by Visco, Div. of Nalco Chemical Co., Sugar Land, 

TX; CDL: 251787-A)

133266. Beavers, J.; Jaber, M.; Joiner, G.; et al. (1983) A Dietary LC50 in the Mallard with EH&S 267: 

Project No. 187-103. Final Report. (Unpublished study received Oct 25, 1983 under 10349-14; prepared 

by Wildlife International, Ltd., submitted by Visco, Div. of Nalco Chemical Co., Sugar Land, TX; CDL: 

251788-A)
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134550. Fletcher, D. (1972) Report to Esso Research and Engineering Company: Acute Oral Toxicity 

Study with MRD 72-10 in Bobwhite Quail: IBT No. J1739. (Unpublished study received Jul 25, 1972 

under 8928-4; prepared by Industrial Bio-Test Laboratories, Inc., submitted by Exxon Chemical 

Americas, Houston, TX; CDL: 005650-D)

470013023. Shapiro, R. (1984) Avian Single Dose LD50 – Bob White Quail: [Armohib B-101]: Report 

No. T-4000. Unpublished study prepared by Product Safety Labs. 14p.

470013024. Shapiro, R. (1984) Avian Dietary LC50 Study with Bob White Quail: Armohib B-101: 

Report No. T-3995. Unpublished study prepared by Product Safety Labs. 6p.

470013025. Shapiro, R. (1984) Avian Dietary LC50 Study with Mallard Ducks: Armohib B-101: Report 

No. T-3998. Unpublished study prepared by Product Safety Labs. 11p.
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Appendix D Chemical and Physical Properties of ATMD 

Compounds

Tables D1, D2, D3, and D4 contain the chemical and physical properties of ATMD Chemicals

Table D1 – Chemical Identification and Product Chemistry of PC Code 067301

Property OCSPP 

Guideline 

No. (unless 

stated)

Value Reference/comments

CAS No. None 61791-63-7 ATMD RED

Molecular weight 

(grams/mol)

None 259.4 49040203

Based on diamine surfactant complex of Mexel 432/0

Water solubility 

(mg/L)

830.7840 ~10 49040204

48486702

Water solubility was approximately 10 mg/l based on diamine surfactant complex

Vapor Pressure 

(VP) (mm Hg)

830.7950 2.88 x 10-4 EPI-Suite 4.11

Weighted average based on % of each C8-C18 component in formulated Mexel 432/0 product and 

Vapor Pressure from EPI_WEB 4.11

Henry’s Law (atm 

m3 mol-1)

None 

(calculated)

9.83 x 10-6 USEPA 201418

[Vapor Pressure (mm Hg) * molecular weight (grams/mol)]/[760 * water solubility (mg/l)]

Log P (unitless) 830.7550 0.2 49040203

Based on weighted average of log P values a % individual diamine content of Mexel 432/0

UV Visible 

absorption (nm)

830.7050 Limited 

sorption

49040202

49208801

ATMD compounds have limited sorption of UV visible light above 290 nm

pK 830.7370 Not 

determined

48486702

Water solubility too low to run test

Table D2 – Chemical Identification and Product Chemistry of PC Code 067302

Property OCSPP 

Guideline 

Value Reference/comments

 

18 USEPA 2014. Risk Assessment for the Proposed Registration of the New Use of ATMD to Control Bio-fouling in Once-Through Cooling Systems and 

Recirculating Cooling Towers. Memorandum dated February 10, 2014. 
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No. (unless 

stated)

CAS No. None 61791-64-8 ATMD RED

Molecular weight 

(grams/mol)

None 276 ATMD RED

Water solubility 

(mg/L)

830.7840 Miscible 44273502

10,000 mg/l used in calculations

Vapor Pressure 

(VP) (mm Hg)

830.7950 1.3 x 10-4 44273502

Henry’s Law (atm 

m3 mol-1)

None 

(calculated)

4.7 x 10-9 10,000 mg/l used in calculations

Vapor Pressure (mm Hg) * molecular weight (grams/mol)]/[760 * water solubility (mg/l)]

Log P (unitless) 830.7550 Not 

applicable 

44273502

Not applicable for polar chemical

UV Visible 

absorption (nm)

830.7050 Limited None

ATMD compounds have limited sorption of UV visible light above 290 nm

pK 830.7370 8.6 4858370

Table D3 – Chemical Identification and Product Chemistry of PC Code 067310

Property OCSPP 

Guideline 

No. (unless

stated)

Value Reference/comments

CAS No. None 68155-37-3 ATMD RED

Molecular weight 

(grams/mol)

None 283.4 

(200-340 )

Calculated

Weighted average based on % of each C8-C18 component. Compound is 1-(alkylamino)-

3-aminopropane)

Water solubility 

(mg/L)

830.7840 40,000 43024503

Vapor Pressure 

(VP) (mm Hg)

830.7950 1.3 x 10-4 43024503

Henry’s Law (atm 

m3 mol-1)

None 

(calculated)

1.2 x 10-9 Calculated

[Vapor Pressure (mm Hg) * molecular weight (grams/mol)]/[760 * water solubility (mg/l)]

Log P (unitless) 830.7550 Not applicable ATMD RED

Not applicable for polar chemical

UV Visible 

absorption (nm)

830.7050 Limited 

absorption

None

ATMD compounds have limited sorption of UV visible light above 290 nm

pK 830.7370 Not available ATMD RED

Complete disassociation in water
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Table D4 – Chemical Identification and Product Chemistry of PC Code 067313

Property OCSPP 

Guideline 

No. (unless 

stated)

Value Reference/comments

CAS No. None 61791-64-8 ATMD RED

Molecular weight 

(grams/mol)

None 283.4 

(200-340 )

Calculated

Weighted average based on % of each C8-C18 component. Compound is 1-(alkylamino)-3-

aminopropane) with two acetic acid groups

Water solubility 

(mg/L)

830.7840 40,000 mg/l 43390601

Vapor Pressure 

(VP) (mm Hg)

830.7950 1.3 x 10-4 44271802

Henry’s Law (atm 

m3 mol-1)

None 

(calculated)

1.2 x 10-9 Calculated

[Vapor Pressure (mm Hg) * molecular weight (grams/mol)]/[760 * water solubility (mg/l)]

Log P (unitless) 830.7550 Not applicable 44271802

Not applicable for polar compounds

UV Visible 

absorption (nm)

830.7050 Limited 

absorption

None

ATMD compounds have limited sorption of UV visible light above 290 nm

pK 830.7370 Complete 

disassociation 

in water

44271802
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Appendix D References 

MRID 42022502. Sinning, D. December 2, 2010. Physical and Chemical Characteristics of 

Mexel 432/0: Color, Physical State, Odor, Oxidation/Reduction: Chemical 

Incompatibility, Flammability, pH, Viscosity, and Relative Density. Project Number: 

4800/01. Unpublished study prepared by Case Consulting Laboratories, Inc. 9 p. 

MRID 43024503. Ellison, F. (1993) Physical and Chemical Characteristics of Duomeen O: 

Physical State, Boiling Point, Specific Gravity, Solubility, Vapor Pressure, pH, and 

Stability: Final Report: Lab Project Number: 00459-001. Unpublished study prepared 

by Case Consulting Labs, Inc. 19 p.

MRID 43022902. Ellison, F. (1993) [N-(coco alkyl)trimethylenediamine]: Physical and 

Chemical Characteristics of [N-(coco alkyl)trimethylenediamine]: Physical State, Boiling 

Point, Specific Gravity, Solubility, Vapor Pressure, pH, Stability, Oxidizing or Reducing, 

Explodability and Viscosity: Final Report: Lab Project Number: 00459-002. Unpublished 

study prepared by Case Consulting Labs, Inc. 19 p.

MRID 43390601. Dsida, P. (1994) Product Chemistry Requirements for 1-((Coco Alkyl) 

Amino)-3-aminopropane Diacetates. Unpublished study prepared by ChemADVISOR, 

Inc. 10 p.

MRID 44271802. Jones, D. (1997) X-Cide 306--Product: Physical & Chemical Characteristics: 

Lab Project Number: C:\X-CIDE\XC_306\XC306ST2.DOC. Unpublished study prepared 

by Petrolite Corp. 5 p.

MRID 44273502. Jones, D. (1997) X-CIDE 305--Product Physical & Chemical Characteristics: 

Lab Project Number: C:\X-CIDE\XC_305\XC305ST2.DOC. Unpublished study prepared 

by Petrolite Corp. 5 p. 

MRID 48486702. Sinning, D. May 16, 2011. Physical and Chemical Characteristics of [N-

(coco alkyl)trimethylenediamine]: Color, Physical State, Odor, Stability, pH, UV/Vis, 

Boiling Point, Density, Dissociation Constant, Octanol/Water Partition Coefficient and 

Solubility: Final Report. Project Number: 4870/02. Unpublished study prepared by Case 

Consulting Laboratories, Inc. 32 p.

MRID 49040202. Murrell, J.R. and W. B. Nixon. April 5, 2012. Determination of the 

Ultraviolet-Visible Absorption Spectrum of [N-(coco alkyl)trimethylenediamine]. 

Wildlife International Project No. 709C-103. Unpublished study conducted by Wildlife 

International, Easton, MD, and submitted by Mexel Industries, Arlington, VA.

MRID 49040203. Farnback, M. July 16, 2012. Determination of the Partition Coefficient (1-

octanol/water) for [N-(coco alkyl)trimethylenediamine]. OCSPP Guideline 830.7550. 
Docket Number EPA-HQ-OPP-2014-0656

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Page 57 of 59

Unpublished study performed by Casco Adhesives AB, Sweden, and submitted by Mexel 

Industries, France.

MRID 49040204. Velea, Luminita. February 26, 2013. Water Solubility for Mexel 432/P, EPA 

Reg. No. 84034-1. Unpublished study performed by Technology Sciences Group, 

Washington, DC, and submitted by Mexel Industries, Arlington, VA.

MRID 49208801. Curcio, L.; Ghillebaert, F. (2013) Requested Supplemental Data for Waiver 

Passing Technical Screen: Photodegradation in Water. Project Number: MEXEL/432/0. 

Unpublished study prepared by Ecotox and The Solutous Group. 34p.

U.S. EPA. September, 2007. Reregistration Eligibility Decision (RED) for 

Alkyltrimethylenediamines (Case 3014). EPA 739-R-07-004.

U.S. EPA. 2012. EPI-Suite 4.11. http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

U.S. EPA. February 10, 2014. Risk Assessment for the Proposed Registration of the New Use of 

ATMD to Control Bio-fouling in Once-Through Cooling Systems and Recirculating 

Cooling Towers. Decision Number 478290 (D415622, D415970, D411969, D416478).

U.S. EPA. 2012. EPI-Suite 4.11. http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
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Appendix E Comments Received 

Concerning the Preliminary Work Plan

On December 19, 2014, EPA opened a 60-day public comment period on the preliminary work 

plan (PWP) for the registration review of ATMD. The comment period ended on February 17, 

2015. During the public comment period the agency received one submission related to the 

ATMD PWP. Table E1 below lists the submitter. 

Table E1. Submitters of Comments on the “ATMD Preliminary Workplan”

Center for Biological Diversity (CBD)

Comment submitted by the Center for Biological Diversity (CBD)

Comment: Under the Endangered Species Act, it is EPA’s duty to consult with the U.S. Fish and 

Wildlife Service and National Marine Fisheries Service on the reregistration of ATMD and approval 

of all ATMD end-use product labels. In addition, the EPA must make defensible “Not Likely to 

Adversely Affect” and “Likely to Adversely Affect” determinations as a prerequisite for 

defensible “Jeopardy” and “No Jeopardy” determinations. EPA and the services must assess the 

adverse impacts of ATMD in critical habitat.

Response: EPA plans to address many of the concerns raised in the comments from Center for 

Biological Diversity as part of the implementation plan for assessing the risks of pesticides to 

listed species based on the recommendations of the April 2013 National Academy of Sciences 

(NAS) report. EPA will address concerns specific to ATMD in connection with the development 

of its registration review decisions for ATMD. The NAS report, available at 

http://www.nap.edu/catalog.php?record_id=18344, outlines recommendations on specific 

scientific and technical issues related to the development of pesticide risk assessments that are 

compliant with the Endangered Species Act and the Federal Insecticide, Fungicide, and

Rodenticide Act. In November, the EPA, along with the U.S. Fish & Wildlife Service (USFWS), 

the National Marine Fisheries Service (NMFS) (collectively, the Services), and the U.S. 

Department of Agriculture (USDA), released a summary of their joint Interim Approaches for 

assessing risks to listed species from pesticides. The Interim Approaches were developed in 

response to the NAS' recommendations and reflect a common approach to risk assessment shared 

by the Agencies as a way of addressing scientific differences between EPA and the Services. The 

joint Interim Approaches were released prior to the stakeholder workshop held on November 15, 

2013. EPA presented the joint Interim Approaches at the December 2013 PPDC and SFIREG 

meetings, allowing additional opportunities for stakeholders to comment on the Interim 

Approaches. The Agencies will consider public comments on the Interim Approaches prior to 

implementing them. The Agencies intend to jointly implement these approaches as part of a 

phased iterative process. EPA will refine its listed species risk assessments based on these 

interim approaches. The details of the joint Interim Approaches are contained in the white paper 
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"Interim Approaches for National-Level Pesticide Endangered Species Act Assessments Based 

on the Recommendations of the National Academy of Sciences April 2013 Report," dated 

November 1, 2013, available at http://www.epa.gov/espp/2013/nas.html.

Regarding the Center for Biological Diversity's request for EPA to begin informal consultation 

with the Services immediately after the workplan for ATMD is finalized, EPA plans to follow 

the March 2013 stakeholder engagement paper ("Enhancing Stakeholder Input in the Pesticide 

Registration Review and ESA Consultation Processes and Development of Economically and 

Technologically Feasible Reasonable and Prudent Alternatives") to identify the appropriate time 

for initiation of consultation, either formal or informal, with the Services. The stakeholder 

engagement paper, jointly developed by the EPA, USDA, and the Services and available at

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2012-0442-0038, allows for 

early interaction with the Services under informal consultation. EPA and the Services 

acknowledge that early interaction as part of informal consultation may result in refinements to 

EPA's effects determinations that can improve the efficiency of the ESA compliance process. For 

example, EPA may involve the Services at the earliest stages of registration review. In general, 

EPA plans to initiate formal ESA consultation, if necessary, at the final decision stage in the 

registration review process. Consulting later in the process allows the EPA to develop more 

refined ecological risk assessments and to engage stakeholders in discussions that should result 

in more focused consultation packages that may include risk mitigation for listed species.