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Page 2 of 59 Alkyl T rimethylenediamines Registration Review Team

Human Health & Environmental Effects Patricia Jennings James Breithaupt Bill Erickson Sumitra Biswas Katelynn King Tim othy Dole Tim othy McMahon

Risk Management Donna Kamarei Zebora Johnson Rose Kyprianou

Office of General Counsel Phil ip RossDocket Number EPA

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Page 3 of 59 TERMS, ABBREVIATIONS AND SYMBOLS

A.I. or a.i. active ingredient ASRI a ctivated sludge r espiration i nhibition BCF b ioconcentration f actor °C d egrees Celsius CAS Chemical Abstracts Service CFR Code of Federal Regulations DCI data call

- in EC 50 m edian (or 50 percent) e ffect c oncentration ECOTOX ECOTOXicology EDSP E ndocrine Disruptor Screening Program E

- FAST Exposure and Fate Assessment Screening Tool EPA Environmental Protection Agency FDA Food and Drug Administration FFDCA Feder al Food, Drug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FWP Final Work Plan g/mol g rams per mole GLN guideline number HPV h igh production v olume IDS Incident Data System Koc o rganic carbon normalized soil

- water partition coefficient Kow o ctanol

- water partition coefficient LC 50 m edian (or 50 percent) l ethal c oncentration LD 50 m edian (or 50 percent) l ethal d ose LOAEC l owest

- o bserved

- a dverse

- e ffect

- c oncentration LOAEL lowest

- observed

- adverse

- e ffect

- l evel Log K ow l ogarithm of the octanol

- water partition coefficient μg m icrogram ml/g m illiliter p er g ram mg/kg m illigram p er k ilogram mg/kg/day m illigram p er k ilogram p er d ay mg/L m illigram p er l iter mm Hg m illimeter of mercury MOE m argin of e xposure MRID Master Record Identification Number MRL m aximum r esidue l imit N/A n ot a pplicable

nm n anometers NOAEC no

- observed

- adverse

- effect

- c oncentration NOAEL n o

- o bserved

- a dverse

- e ffect

- l evel 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 h ydrogen or power of the con centration of the hydrogen ion pKa p ower of the acid dissociation constant or negative base

- 10 logarithm of the acid

dissociation constant of a solution ppb p arts p er b illionDocket Number EPA

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Page 4 of 59 ppm p arts p e r m illion PWP Preliminary Work Plan QSAR q uantitative s tructure

- a ctivity r elationship RED Rere gistration Eligibility Decision SAR s tructure a ctivity r elationship SF s afety f

actor TGAI t echnical grade active i ngredient TMDL total maximum daily l oad s TOR Threshold of Regulation UF uncertainty factor UV/VIS ultraviolet/v isible light a bsorption WWTPs w astewater treatment plantsDocket Number EPA

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Page 5 of 59 

### 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 He alth

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

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

................................ ................................ ................................ ......... 13 3 Human Health Risk Assessment

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

................................ ................................ ................................ . 17 3.2 Diet ary Exposure

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

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

................................ ................................ ................................ ........ 18 3.3 Occu pational 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 T oxicology Profile

................................ ................................ ............................... 28 Appendix B Environmental Fate

................................ ................................ .............................. 38 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 44 Appendix D Chemical and Physical Properties of ATMD Compounds

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Page 6 of 59 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

................................ ................................ .......... 22Docket Number EPA

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## 1 Introduction

This document is the United States Environmental Protection Agency ’s ( USEPA, EPA or “the agency ”) Final Work Plan ( F WP) for a lkyl trimethylenediamines , herein referred to as ATMD

. The FWP document explains what EPA's Office of Pesticide Programs (OPP) knows about ATMD , high lighting 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 inf ormation 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 po licies 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. Throu gh 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/pesticide

reevaluation

.
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 standa rd for registration. The regulations governing registration review begin at 40 CF R 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 eac h 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 ag ency’s response to comments submitted regarding the PWP.Docket Number EPA

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Page 8 of 59  Corrected formatting and typographical errors.

The agency received one submission during the public comment period on th e initial docket. See Appendix E for the agency’s response to this comment.

C omments 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

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. Tables 1 and 2 b elow 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 detail s)

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

Dietary (drinking water) Yes 2/10/201 4 1 Updated Developmental t oxicity
, reproduction and fertility e ffects , n eurotoxicity, chronic
t oxicity , and c arcinogenicity (Note: these data exist, however EPA does not have access to the full reports)

Occupational Handler (Liquid Products) No (see 3.3.1 ) 2/10/2014 1 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

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Page 9 of 59 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 detail s)

Ecological Yes 2/10/2014 1 Updated Aerobic aquatic metabolism, anaerobic aquatic metabolism, leaching

- adsorption

desorption, r eady biodegradability , p orous pot , s imulation test

— activated sludge units
, s imula tion test

—

primary and ultimate, b iodegradability , activated sludge respiration inhibition (ASRI), cyanobacteria toxicity, and

w ho le sediment subchronic toxicity

— freshwater amphipod

1 U.S. EPA
, February 10, 2014 The alkyl trimethylenediamines in this case are used primarily as microbi o cide s , bactericide s , or mollusci ci de s 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, 201 4 in support of a proposed new use to control bio

- fouling in once

- through cooling systems and recirculating cooling
towers. For th is assessment, the agency received summaries and not full studies for several key toxicity studies and default assumptions were used in lieu of some environmenta l 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 agen cy can determine whether the active ingredients continue to meet the standard for registration as well as allow the agency to make end angered 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 Preli minary 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 20 20

- 06 Open 30

- Day Public Comment Period for Preliminary Risk Assessment(s) 20 21

- 12
Close Public Comment Period 202 2

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Page 10 of 59 Phase 3: Registration Review Decision and Implementation Open 60

- Day Public Comment Period for Pro posed 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 ( P C c ode 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 c ode 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 physi cal 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

m 3 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 determined 2 Complete disassociation in water

1 [Vapor Pressure (mm Hg) * molecular weight (grams/mol)] / [760 * water solubility (mg/l)]
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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 EUP s are liq uids and one EUP is a solid. The solid product is formulated as pellets/balls that range in d iameter 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 prod ucts 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 Thr u) Meter in /I nject Liquids 0.042

Commercial/Industrial Water Cooling Systems (Recirculating) Meter in /I nject Liquids 143 (shock/slug) 14 ( continuous )

Disposal Systems Meter in /I nject Liquids 143 (shock/slug) 14 ( continuous )

Fuels/oil storage tanks bottom water Meter in /I nject Liquids Open Pour Solids 1.6 to 32

Oil Recovery Drilling Muds/Packer Fluids Meter in /I nject Liquids 64 to 722 Pipelines (non pig g able 1 ) Meter in /I nject Liquids 65

Secondary Oil Recovery Injection Water Meter in /I nject Liquids 8 to 212 (shock/slug) 14 to 400 ( continuous )Docket Number EPA

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Page 12 of 59 Waterfloods and Salt Water Disposal Systems Meter in /I nject 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 f or ATMD.



## 1.6 Regulatory Histor y

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 200 7

. 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 co nveyor 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 h igher are reported in individual reports which include information regarding the causes of the inci dent 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 (sear ch conducted on 9/18/14). All three incidents were caused by operator error during product transfer that caused the product to be spray ed out of the transfer hose and onto employees

. In two of these incidents
, the employees suffered ocular burns which were resolved after t reatment

. I n theDocket Number EPA

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Page 13 of 59 third incident
, the employees required over the counter medication after being decontaminat ed in a safety shower and examined in a hospita l

. 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 t ime period (often quarterly). Typical ly 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 spill age or transfer pump failure while the cause of the third incident was not repo rted

. 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

a gency’s IDS as of September 1, 2014.


## 2 A nticipated Data Needs

The ATMD chemicals in this case span a range of uses and physical/chemical properties. The agency expects to require e nvironmental fate data for all PC codes. Data for PC c ode 067301 are anticipated to be required since it is the only ATMD chemical with re latively

- 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 requirement s

. PC c ode 067310 is anticipat ed to be used as the surrogate for miscible ATMD chemical s , because it is a high production volume (HPV) chemical

. I t 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 biodegrad ability study (MRID 49040207). However, since
t his 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 M odule

. Data is necessary to refine the risk assessment. T he a gency 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

. T he regi strant 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) . I n accordance with guidelines published by the Office of Pesticide Progr ams on citation of open scientific literature ( http://www.epa.gov/pesticides/science/lit

- studies.pdf ), i nformation from the open literature should be presented as the full article and no t a summary. Therefore, the agency anticipates theDocket Number EPA

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Page 14 of 59 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 bel ow.

Since no environmental fate data for PC codes 067302, 067310, or 067313 have been submitted to the a gency, environmental fate data listed in Table 6 are anticipated as being required
, including: (1) aerobic aquatic metabolism; (2) anaerobic aquatic metabolism; (3) leaching

- adsorption

desorption; (4) biodegradability during wastewater trea tment; and (5) activated sludge respiration inhibition. Since these compounds are polar chemical s 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.Docket Number EPA

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Page 15 of 59 Table 6

– Anticipated Data Needs for the Registration Review of ATMD Chemicals

GLN Study Name Test Substance Time Frame 1 (Months) Risk Assessment(s) Data

Will Support Use Site(s) Triggering Anticipated Data Requirement Applicable Exposure Scenario

835.4300 Aerobic aquatic metabolism TGAI 4 24 Ecological Cooling towers, oil

- field uses Ecological Exposure

- IPWS

835.4400 Anaerobic aquatic metabolism TGAI 4 24 Ecological Cooling towers, oil

- field uses Ecological Exposure

- IPWS

835.1230 Leaching

- adsorption

- desorpt i on TGAI 5 12 Ecological Cooling towers, oil

- field uses Ecological Exposure

- IPWS

835.3110 2 ,3 835.3220 835.3240 835.3280 Biodegradability in WWTP TGAI 4 12 Ecological Cooling towers, oil

- field uses Ecological Exposure

- IPWS

850.3300 Activated Sludge Respiration

Inhibition (ASRI) TGAI 4 12 Ecological Cooling towers, oil

- field uses Ecological Exposure

- IPWS

850.4550 Cyanobacteria toxicity TGAI 4 12 Ecological Cooling towers, oil

- field uses Aquatic environment

- aquatic plants

850.1735 Whole sediment subchronic

toxicity, freshwater amphipod TGAI 6 12 Ecological Cooling towers, oil

- field uses Aquatic environment

- benthic invertebrates

870.3700 Developmental Toxicity 7 TGAI 24 Dietary Cooling towers
, oil

- field uses Drinking Water

870.3800 Reproduction and Fertility

Effects 7 TGAI 48 Dietary Cooling towers
, oil

- field uses Drinking Water

870.6200 Neurotoxicity Study 7 TGAI 12 Dietary Cooling towers
, oil

- field uses Drinking Water

870.4100 Chronic Toxicity 7 TGAI 48 Dietary Cooling towers
, oil

- field uses Drinking Water

870.4200 Carcinogenicity 7 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 code s 067302, 067310 , and 067313 , t he results of the Activated Sludge Respiration Inhibition Test (ASRI) will determine which of these four biodegradation tests is/are anticipated to be required.Docket Number EPA

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Page 16 of 59  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 regi strant must conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test

- Aer obic 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 antimicrob ial 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 r eady biodegradability study (MRID 49040207 ) was conducted for PC c ode 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 0 67301, 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 0 67301 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 T hese data exist, however EPA does not have access to the f ull reports

. Data on any of the four PC codes ( 067301, 067302, 067310, 067313) may be submitted to satisfy the requirement.Docket Number EPA

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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 once

through 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 ri sk assessment performed by the a gency in support of this registration d ecision, EPA did not identify risk s of concern for the proposed use.

In the 201 4 risk assessment, t he information submitted for assessment of human health hazard on ATMD consisted largely of summaries of toxicity studies conducted in experimen tal 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/pestici des/science/lit

studies.pdf

) describes the adequacy of scientific literature studies submitted in support of a human health risk assessment. I nformation from the open literature should be presented as the full article and not a summary. All of the cited st udies from the 2008 European Commission risk
assessment were submitted as summaries only. This hinders a full haza rd evaluation and dose

response assessment of the mammalian toxicity data for ATMD

. The agency anticipates requiring the full published articl es 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 a gency’s most recent risk assessment in support o f 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) Antimi crobials 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 ce rtain ATMD structural analogs. The agencyDocket Number EPA

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Page 18 of 59 has determined t hat 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 rel ated 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 a lso consists of a repeated dose toxicity study with developmental and reproductive screening (MRID 47646101) submitted on coc o 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 intra

species 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

mes enteric lymph node, spleen, bone marrow (sternum) and trachea

. 

## 3.2 Dietary Exposure

The a gency has previously conducted a dietary (drinking water only ) exposure and risk assessment for ATMD ( PC code 067301 ) (US EPA, 2014)

. However, s ince the a gency has not conducted a n 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. Alt hough 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 l abels, 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 a n assessment of the potential for exposure and risk to humans from ingestion of drinking water conducted by the a gency 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

c o de 067301 in once

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Page 19 of 59 The a gency has not conducted a n analysis of potential exposure and risk from ingestion of drinking water by humans for the other uses and chemicals considered in this ca se. H owever, a n 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 r isks to humans from ingestion of drinking water, the

a gency 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

Occupatio nal 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 a gency 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 (492 45

- 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 formul ation (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 exp ected 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.Docket Number EPA

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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

c ommon 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

- (coco alkyl) trimethylenediamine (PC c ode 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 tower s and once

through cooling systems. T he agency has not co nducted a risk assessment for the other chemicals and uses in this case (i.e., c ase 3014).

The a gency 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 a gency to determine potential acute and chronic risks to aquatic organisms potentially expos ed in the aquatic environment. The risk assessment will allow the

a gency to determine whether the uses of ATMDs h ave '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 a gency 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 c ase are used primarily as microbi o cide s , bactericide s , or mollusci ci de s in industrial cooling water systems (recirculating and once

- through) and for oilfield uses. Based on the chemical structure, a s 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 requ ired 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

- (coco alkyl) trimethylenediamine (PC c ode 067301). The environmental fate data for this

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Page 21 of 59 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, t here is limited potential for bioconcentration of N

- (cocoalkyl) trimethylenediamine in fish

. Based on the vapor pressure and Henry’s Law values in Table 3
, n one of the ATMD chemical s 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 E nvironmental 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 chemical s can occur f rom the industrial cooling water system and oil field uses. For the industrial cooling water system use s (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 c hemicals and is subsequently land

- applied

. For the oil field use s , 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 chemical s in surface waters and aquatic sediments downstream fro m 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 Env ironmental Exposure Pathways of Antimicrobial Pesticides” (EPA

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- 0002) , found at www.regulations.gov in docket EPA

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. For once

through 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 wat er, refer to slides 19 and 20. For non

- piggable pipelines, refer to slide 23. All relevant routes of environmental exposure will be con sidered in the risk assessment.

4 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885
5 http://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/Docket Number EPA

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## 4.3 Ecological Effects Assessment

4.3.1 Mechanism of Action

The a gency is not aware of the mode of action of ATMD chemical s 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 chemical s to plants and animals

. All available ecotoxicity endpoints are tabulated in Appendix C. For most requirements, data are br i dged among the four PC codes. However, PC c ode 067301 is the only ATMD expected to bind to soils and sediments; therefore, sediment toxicity tes ts are anticipated to be needed only for that PC c ode.

OPP uses the most sensitive endpoints for assessing risk s. The available endpoints for the ATMD chemical s 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 LC 50 = 0.03 m g ai/L 133265 and 41786601 Freshwater fish TGAI Chronic NOAEC = 0.004 mg ai /L 49208804

Freshwater invertebrates TGAI Acute EC 50 = 0.051 m g ai/L 41786602
Chronic NOAEC = 0.0 16 mg ai/L 49040208

Estuarine/marine fish TGAI Acute LC 50 = 0.155 mg ai/L 41786604
Chronic Not required

--

Estuarine/marine invertebrates TGAI Acute EC 50 = 0.019 mg ai/L 41786605 and 41786603
Chronic Not required

--
Aquatic plants, vascular TGAI EC 50 and NOAEC EC 50 = 0.123 mg ai/L

NOAEC = 0.020 mg ai/L 49040213
Aquatic plants,

non

- vascular TGAI EC50 and NOAEC EC 50 = 0.0052 mg ai/L

NOAEC = 0.0024 mg ai/L 49040216

Sediment

- dwelling invertebrates TGAI Subchronic EC 50 = 188 mg ai/kg NOAEC = 16 mg ai/kg 49040211

Birds TGAI Acute LD 50 = 0.24 mg ai/kg 470013023Docket Number EPA

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### 4.3.3 Open L iterature 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 evalua ted in the risk
assessment. Use of open literature is dis cussed in more detail on the agency’s website: http://www.epa.gov/pesticides/science/efe d/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 Fat e Assessment Screening Tool) to determine the number of days of exceedance of ATMD concentrations of concern for aquatic organisms to predict the potential for ex posures 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 curr ently available, as stated in se ction 4.4.2
, a screening

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

.
The a gency has conducted a risk assessment for ATMD (PC code 067301) used to control bio

fouling 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 a gency expects to use the General Population and Ecological Expos ure 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 f or aquatic animals and plants. The method used to estimate environ mental 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 sin ce 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

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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, orga n 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 FFDC A 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 c onsists 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

- rela ted 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, 2013 7 and includes some pesticides schedul ed 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

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- 0074 for the final second list of chemicals.
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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 d ata, 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 Rel ative 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)trimethylenediam ine] : 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 S pectrum 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: ECOTOXi cology 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.htmDocket Number EPA

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Page 27 of 59 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 T oxicology 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 a ssigned 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, tem porary 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%] andDocket Number EPA

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Page 29 of 59 food consumption [16%] compared to the corresponding controls. No change was seen in the females.

No test item related effect occurred in hema tology 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 ad renal 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 anima ls, macroscopic findings observed were considered to be spontaneous and not treatment related

. Histopathologically, test item

related changes were seen in the small intestine (ileum and jejunum), mesenteric lymph node, spleen, bone marrow (sternum) and tr achea 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 m arrow (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 tal low 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 beDocket Number EPA

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Page 30 of 59 sacrificed and necropsied after treatment on gestation day 15 to determine the appearance and severity of gastrointestinal tract irritation. On gestatio n 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.”

“A ll 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, sal ivation, 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 pron ounced 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 weig ht 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. Feta l 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 dose

dependent 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

r egistrant 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 (S D) 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.Docket Number EPA

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Page 31 of 59 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 contr ol 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 w as 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 prematin g 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 anima ls 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 diff erences 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 perform ed 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 sacrific ed, 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 pre

implantation loss was not evaluated. Staining for the presence of implantation sites was only performed with t he 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 14.3Docket Number EPA

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Page 32 of 59 in the control, the 12.5 and the 50 mg/kg /day dose groups. Thus, the mean litter index for post

implantation loss was calculated to 3.4, 9.9 and 4.5% i n 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 v alues 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 statistica lly 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 der ived 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 s tudy, 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 Pro grams (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 S ummary 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 dose s 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 recei ved 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 f ollowed by motor activity testing on the day of scheduled sacrifice.Docket Number EPA

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Page 33 of 59 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, ungroo med 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 a nimals, 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 gestati on, 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%, respectiv ely, 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 les s 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 weig ht 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 hig h

- 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 stre ngths, 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 contr ol 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 se en 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) l iver, 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 weight

relative

- to

- body weight of the testes, brain, and adrenals, although the absolute weight of th ese 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 i ncidence 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 fe males. Dose

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Page 34 of 59 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 tr eated 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 lu tea 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 cl inical 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/da y for lactation days 1

- 4 (1.8 g vs 3.0 g for controls). No treatment

related 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 stoma ch, 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 fem ale 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 che mical 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 weig hts were recorded. Gross and microscopic examinations were made on major tissues (20 organs/tissues).Docket Number EPA

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Page 35 of 59 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 co nsisting 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 t oxic 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 com parable 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 organ s 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 c ell 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 mesent eric 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 treatment

related. Therefore a NOAEL of 200 ppm (10 mg/kg /day ) is proposed for the 2

- year rat studies.

In a third study, th ree 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 unt reated 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 do g 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 mortalityDocket Number EPA

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Page 36 of 59 associated with anorexia and hemorrhagic diarrhea in one dog, growth depression in two other dogs, and the lymph nod e 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 ingr edient 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 toxicit y study of octadecylamine ("stearamine") was conducted using Sprague

Dawley 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

- 3 3% 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 informati on 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 dat abase 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 structure

activity 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 pi ece 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 maj or 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 sma ll 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.”Docket Number EPA

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Page 37 of 59 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.

MRID 49092802 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.Docket Number EPA

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Page 38 of 59 

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of ATMD Compounds

Environmental Fate Assessment
The alkyl trimethylenediamines are used primarily as microbiocides , bactericide s , or mollusci ci de s in industrial cooling towers (recirculating and once

- through) and for oilfield uses. As a group, ATMD chemical s are not susceptible to degradation by abiotic processes (hydrolysis and photodegradation in water)

. 10 No u seable data have been submitted to demonstrate potential biotic degradation for all ATMD chemical s.
The only ATMD chemical for which environmental fate data have been submitted is N

- (coco alkyl) trimethylenediamine (PC c ode 067301). The se environmental fate data demonstrate that it is strongly sorbed to soil, sediment, and sludge and it is not readily biodegradable in
wastewater treatment plants (WWTP s). 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 bec ause of the lack of data. The only ATMD chemical with data on sorption to soil or sediment is N

- (cocoalkyl) trimethylenediamine (PC c ode 067301) , which has been demonstrated to be tightly sorbed

. Based on a bioconcentration study, t here 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 c odes and soil and sediment absorption/desorption i sotherm data (835.1230) for the t hree miscible compounds ( PC

c ode s 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 c ode 067301) with an IC 50 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 a gency is also requiring additional ASRI testing for all PC codes because the 95 % confidence intervals w e re too wide. In addition, the a gency anticipates requiring an Activated Sludge Respiration Inhibition (ASRI) test for PC code s 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, 49040207Docket Number EPA

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Page 39 of 59 Based on the vapor pressure and Henry’s Law values in Table 3
, n one of the ATMD chemicals

ar e 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 c ode 06730 1). It was stable to hydrolysis at pH 5, 7, and 9 (MRIDs 40062413 and 41069001). Based on the chemical structure of all ATMD chemical s in th is case (3014) , none are expected to be likely to degrade by hydrolysis and no additional hydrolysis data

are anticipated to be required.

Aqu eous Photoly s is
Data on photodegradation in water (OCSPP 835.2240) have not been submitted for any of the ATMD chemical s but none are expected to photodegrade directly bas ed on their chemical
structure. Therefore, photodegra dation in water data are not anticipated to be required.

Octanol

- Water Partition Coefficient and Bioconcentration in Fish

The log P (log Kow) for ATMD chemical s can vary with the length of the alkyl chain, which includes 8 to 18 carbons (C 8 - C 18 ). For all ATMD chemicals in this case except 067301, the log P is not applicable because the se are polar chemical s. However, for PC c ode 067301, the log P is 0.2 which represents a weighted average of the percent alkyl chain length. The log P ranged from

- 3 (C 8 ) to 2.5 (C 18 ) (MRID 49040203).

Based on this average log P, the re is limited bioconcentration of N

- (cocoalkyl) trimethylenediamine in fish with BCF values of 180

- 525X (MRID 49040210).

Aerobic Aquatic Metabolism

D ata on aerobic aquatic metabolism (OCS PP 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

.
A n a erobic Aquatic Metabolism

D ata on an aerobic aquatic metabolism (OCSPP 835.4 4 00) 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.Docket Number EPA

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Page 40 of 59 Soil
Soil Leaching/Adsorption/Desorption Batch Equilibrium
Data on leaching

- adsorption

- desorption were not submitted for any of the ATMD chemical s except for N

- coco

- 1,3

- diaminopropane (PC c ode 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 R 2 values of 0.88

- 0.97 (Table B 1 be low). Sorption was most closely related to the cation exchange capacity (CEC) of the soils (r 2 =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 49 040206).
Data on sorption to soil and sediments are anticipated to be required for PC code s 067302, 067310, and 067313

.
Aerobic Soil Metabolism

Data on aerobic soil metabolism (OCSPP 835.4100) h ave not been submitted for these ATMD chemical s and are not anticipated to be required because the use patterns are not expected to lead to significant releases to the soil environment.

A n a erobic Soil Metabolism

Data on anaerobic soil metabolism (OCSPP 835.4200) have not been submitted for these ATMD chemical s 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 c ode 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.htmDocket Number EPA

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Page 41 of 59 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 c ode 067301) . To fulfill the data requirement for biodegradability in a wastewater tr eatment 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 c ode 067301 did not demonstrate the potential to readily biodegrade, the results from the Activated Sludge Sorpt ion 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 wo uld 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 a gency to consider removal via biodegradation during waste water treatment, data from a WWTP biodegradation simulation test is required.
Wastewater treatment plant b iodegradability data on PC code s 067302, 067310, and 067313 are anticipated to be required

. The outcome of the ASRI test will determine whether a rea dy 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 c ode 067301) with an IC 50 of 21.9 mg/l (>20) (MRID 49040218). MRID 49040218 was considered to contain supplemental data only because the confidence bounds on the IC 50 value of 22 mg/l (10

- 30 mg/l) are too wide
, based on the fact that an IC 50 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 IC 50 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.Docket Number EPA

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Page 42 of 59 Table B1. Environ mental 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 required 13 None

Photodegradation on soil 835.2410 Not required 14 None

Aerobic soil metabolism 835.4100 No data None

Anaerobic soil metabolism 835.4200 No data None

Aerobic aquatic metabolism 835.4300 No data 15 49208802

Anaerobic aquatic metabolism 835.4400 No data 16 49208803

Leaching

adsorption

desorption 835.1230 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 l ack 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 f or EPA’s exposure assessment.Docket Number EPA

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Page 43 of 59 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 Ace tate: 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 Nu mber: 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

- diamino

diamineopropane (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)t rimethylenediamine] : 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 Prote ction Agency, Washington, DC, USA

. http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

US EPA, February 10, 201 4

. 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

.Docket Number EPA

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Page 44 of 59 

# Appendix C Ecotoxicology Profile

The available ecotoxicity data are tabulated below for each receptor group. Data are bridged among the PC c odes for all receptor groups except se diment

- dwelling invertebrates. PC c ode 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 c ode.


### Toxicity to Terrestrial O rganisms

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) LD 50

(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 non toxic 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) LC 50

(ppm) Toxicity

Category EPA Study ID

Northern bobwhite ( Colinus virginianus ) 100 6400 Practically nontoxic 470013024 Acceptable

32 6400 Practically nontoxic 40062405 AcceptableDocket Number EPA

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Page 45 of 59 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 pesticide s with wood preservative uses. Because the ATMDs have no wood preservative uses, data are not anticipated to be required

. 

### Toxicity to Aquatic Organ isms

Freshwater Fish
The available acute toxicity studies categorize the AMTDs as being slightly to hi ghly 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 41786606 Acceptable

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 SupplementalDocket Number EPA

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Page 46 of 59 0.03 1390 Practically nontoxic 123862 Acceptable

Chronic data are ava ilable 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 toxi c to freshwater invertebrates. One chronic study found no adverse effects on daphnid reproduction or growth at conce ntrations 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 Toxici ty

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 49040208 AcceptableDocket Number EPA

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Page 47 of 59 Estuarine/Marine Fish and Invertebrates

The available studies categorize t he 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) i s 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 di atom, and a marine diatom. Data for cyan obacteria are not available. In the absence of an ecotoxicity study for cyanobacteria, Web

- ICE 17 was previously used to predict an EC50 = 0.012 mg ai/L. However, that prediction does not satisfy the guideline (85 0.4550). A study with cyanobacteria is antic ipated as being needed.

17 Web

- ICE (EPA 2013 ); http://www.epa.gov/ceampubl/fchain/webice/Docket Number EPA

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Page 48 of 59 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 c ode 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
compou nds 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 ( L eptocheirus 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.Docket Number EPA

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Page 49 of 59 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 prepa red 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 prepar ed 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 D ata 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 Estuar ine 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 Labor atories. 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 Industrie s, SAS: C/O Mexel USA, LLC.Docket Number EPA

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Page 50 of 59 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: 709 A

- 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 (L eptocheirus plumulosus ) Using Spiked Sediment. Wildlif e 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 Fre shwater 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 To xicity 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): Laborator y 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: R ainbow Trout: 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

- A)

97519. Casterton, P.L. (1979) Fish Acu te 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. (19 79) 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)Docket Number EPA

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Page 51 of 59 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, Tu lsa, 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 b y 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 Industria l 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 receive d 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 . (Unpubl ished 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. (Unpubli shed 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; submitt ed 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 ). (Unpubli shed 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: Sta tic 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 C o., Sugar Land, TX; CDL: 251788

- A)Docket Number EPA

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Page 52 of 59 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 I ndustrial 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 Safe ty 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.Docket Number EPA

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Page 53 of 59 

# Appendix D Chemical and Physical Properties of ATMD Compounds

Table s D1, D2, D3, and D 4 contain the chemical and physical properties of ATMD Chemicals

Table D 1

– Ch emical 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

m 3 mol

- 1 ) None

(calculated) 9.83 x 10

- 6 USEPA 2014 18 [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

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Page 54 of 59

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

m 3 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 C 8 - C 18 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

m 3 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 waterDocket Number EPA

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Page 55 of 59 Table D 4

– 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 C 8 - C 18 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

m 3 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 44271802Docket Number EPA

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Page 56 of 59 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 pr epared 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 al kyl)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 st udy 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 o f [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

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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 Solubil ity 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 Waive r 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.htmDocket Number EPA

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Page 58 of 59 

# 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 defens ible “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 diffe rences 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 oppor tunities 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 paperDocket Number EPA

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Page 59 of 59 "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 E SA 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 enga gement paper, jointly developed by the EPA, USDA, and the Services and available at http://www.regulations.gov/#!documentDetail;D=EPA

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- 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. Consul ting 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.