Page 2 of 50

1,3

- Propanediamine, N

- (3

- aminopropyl)

- N

- dodecyl

- Registration Review Team

Human Health & Environmental Effects Jenny Tao Nate Mottl Don Wilbur Patricia Jennings James Breithaupt William Erickson Srinivas Gowd a

Risk Management Tina Pham James Par ker Emilia Oiguenblik Velma Noble

Office of General Counsel Philip RossDocket Number EPA

- HQ

- OPP

- 2014

- 0406

www.regulations.gov

Page 3 of 50 TERMS, ABBREVIATIONS AND SYMBOLS

AD Antimicrobials Division A.I. or a.i. active ingredient aPAD a cute p opulation a djusted d ose ASRI a ctiva ted sludge r espiration i nhibition
atm

- m 3 /mole a tmospheric pressure

- cubic meter per mole BCF b ioconcentration f actor °C d egrees Celsius CAS Chemical Abstracts Service CFR Code of Federal Regulations CHO Chinese h amster o vary CMA Chemical Manufact urers Association CO 2 c arbon dioxide COC c oncentration

- of

- c oncern cPAD c hronic p opulation a djusted d ose DCI data call

- in EC 50 m edian (or 50 percent) e ffect c oncentration EC 05 5 p ercent e ffect c oncentration ECOTOX ECOTOXicology EDI e stimated daily i ntake EDSP E ndocrine Disruptor Screening Program E

- FAST Exposure and Fate Assessment Screening Tool EPI Suite Estimation Program Interface Suite EPA Environmental Protection Agency FDA Food and Drug Administration FFDCA Feder al Food, Drug, and Cos metic 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 normalize d soil

- water partition coefficient Kd s oil

- 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 L OEC l owest

- o bserved

- 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 NumberPage 4 of 50

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 dve rse

- 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 PAD p opulation a djusted d ose PAI p ure active i ngredient PDM Probabilistic Dilution Model % p ercent PC Code Pesticide Chemical Code PCF p ounds p er c ubic foot pH power of h ydrogen or power of the con centration of the hydrogen ion PHED Pesticide Handler’s Exposure Data PIS primary i rritation s core pKa p ower of the acid dissociation co nstant or negative base

- 10 logarithm of the acid

dissociation constant of a solution ppb p arts p er b illion
ppm p arts p er 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 SSTS Section Seven Tracking System TEP t ypical e nd

- u se p roduct TGAI t echnical grade active i ngredient TMDL total maximum daily l oads UF uncertainty factor UV/VIS ultraviolet/v isible light a bsorption % w / w p ercent weight per weight. WP w ettable powder WWTPs w astewater treatment plants 1,3

- PAD 1,3

- propanediamine, N

- (3

- aminopropyl)

- N

- dodecyl

-Page 5 of 50



### Table of Contents
1 Introduction

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

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

................................ ................................ ................................ ................. 9 1.3 Chemical Identif

ication and Properties

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

................................ ................................ ................................ ... 10 1.4.1 Registrations

................................ ................................ ................................ ........... 10 1.4.2 Summary of Registered Uses

................................ ................................ .................. 10 1.4.3 Usage Information

................................ ................................ ................................ .. 11 1.5 Regulatory History

................................ ................................ ................................ ......... 11 1.5.1 Tolerance Information

................................ ................................ ............................ 11 1.6 Incidents

................................ ................................ ................................ ......................... 12 1.6.1 Human Health

................................ ................................ ................................ ......... 12 1.6.2 Ecological

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

................................ ................................ ................................ ........ 12 3 Human Health Risk Assessment

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

................................ ................................ .................. 15 3.2 Dietary Exposure

................................ ................................ ................................ ............ 15 3.2.1 Food

................................ ................................ ................................ ........................ 16 3.2.2 Drinking Water

................................ ................................ ................................ ....... 16 3.3 Occupational and Residential Exposures

................................ ................................ ....... 16 3.3.1 Occupational Handler Exposure

................................ ................................ ............. 17 3.3.2 Occupational Post

- application

................................ ................................ ..................... 17 3.3.3 Residential Handler Exposures

................................ ................................ .................... 17 3.3.4 Residential Post

- Application Exposures

................................ ................................ ...... 17 3.4 Aggregate and Cumulative Exposure

................................ ................................ ............. 18 3.4.1 Aggregate Exposures

................................ ................................ .............................. 18 3.4.2 Cumulative Exposures

................................ ................................ ............................ 18 4 Environmental Risk Assessment

................................ ................................ ........................... 18 4.1 Environmental Fate Assessment

................................ ................................ .................... 19 4.1.1 Water Quality

................................ ................................ ................................ .......... 19 4.2 Environmental Exposure Pathwa ys

................................ ................................ ................ 19 4.2.1 Ecological Effects Assessment

................................ ................................ ............... 20 4.2.2 Mechanism of Action

................................ ................................ .............................. 20 4.3 Exposure Analysis Plan

................................ ................................ ................................ .. 20 4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates

................................ ............ 20 4.3.2 Screening Level Down

- the

- D rain Analysis

................................ ............................ 21 4.4 Effects Analysis Plan

................................ ................................ ................................ ..... 21 5 Endocrine Disruptor Screening Program (EDSP)

................................ ................................ . 22 6 Optional Label Changes

................................ ................................ ................................ ........ 23 7 Guidance for Commenters

................................ ................................ ................................ .... 23 7.1 Preliminary Work Plan

................................ ................................ ................................ ... 23 7.1.1 Trade Irritants

................................ ................................ ................................ .......... 23 7.1.2 Water Quality

................................ ................................ ................................ .......... 23 7.1.3 Environmental Justice

................................ ................................ ............................. 23 7.1.4 Structure Activity Relationships

................................ ................................ ............. 24Page 6 of 50

7.1.5 Additional Information

................................ ................................ ........................... 25 8 Next Steps

................................ ................................ ................................ ............................. 25 9 References

................................ ................................ ................................ ............................. 26

Appendix A T oxicology Profile

................................ ................................ ............................... 27 Appendix B Environmental Fate

................................ ................................ ............................. 41 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 45 Appendix D Screening Level Down

- the

- Drain Analysis

................................ ........................ 48 Appendix E Product Chemistry

................................ ................................ ............................... 49

List of Tables Table 1

– Summary of Anticipa ted Risk Assessments and Data Needs for Registration Review: 1,3

- PAD

................................ ................................ ................................ ................................ .......... 8 Table 2

– Anticipated Registration Review Schedule

................................ ................................ .... 8 Table 3

– Chemical Identification of 1,3

- Propanediamine,N

- (3

- aminopropyl)

- N

- dodecyl

- .......... 9 Table 4

– Physical

- Chemical and Environmental Fate Properties for 1,3

- Propanediamine, N

- (3

- aminopropyl)

- N

- dodecy l

- ................................ ................................ ................................ ............. 10 Table 5

– Summary of 1,3

- PAD Registered Uses

................................ ................................ ........ 10 Table 6

– Studies Anticipated as Needed for the Registration Review of 1,3

- P AD

.................... 13 Table 7

– Existing Toxicological Endpoints for 1,3

- PAD

................................ ............................ 15 Table 8

– Occupational Handler Exposure Scenarios for 1,3

- PAD

................................ .............. 17 Table 9

- Residential Post

- Application Exposure Scenarios for 1,3

- PAD

................................ ... 18 Table 10

– Ecological Effects Endpoints

................................ ................................ ....................... 20 Table 11

– Acute Toxicity Studies for 1,3

- PAD

................................ ................................ ........... 27 Table 12

– Toxicology Profile for 1,3

- PAD

................................ ................................ ................. 38 Table 13

– Summary of Chemical, Physical, and Environmental Fate Properties

....................... 42 Table 14

– Product Chemistry of 1,3

- Propanediamine,N1

- (3

- aminopropyl)

- N1

- dodecyl

- ......... 49Page 7 of 50



## 1 Introduction

This document is the United States Environmental Protection Agency ’s ( USEPA, EPA or “the
agency ”) Preliminary Work Plan (PWP) for 1,3

- Propanediamine, N

- (3

- aminopropyl)

- N

- dodecyl

-

, herein referred to as 1,3

- PAD

. T he PWP documen t explains what EPA's Office of Pesticide Programs (OPP) knows about 1,3

- PAD , highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the agency in conducting the review, and providing an anticipated timeline for completing 1,3

- PAD ’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 1,3

- PAD and what types of new data or other information would be helpful for the agency to receive as it moves toward a decision on 1,3

- PA D

. The agency encourages all interested stakeholders to review the PWP and to provide comments and additional information that will help the agency ’s decision

- making process for this chemical.



## 1.1 Statutory and Regulatory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides di stributed 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 rev iew program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/

.
The agency is implementing the registration review program pursuant to Section 3(g) of the Federa l Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 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 each case. The docket is the
agency ’s opportunity to state what it knows about the pestici de and what additional risk analyses and data or information it believes are needed to make a registration review decision. After reviewing and responding to comments and data received in the docket during this initial comment period, the agency will devel op a F inal W ork P lan (FWP) which will include an anticipated schedule for the 1,3

- PAD case

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

- HQ

- OPP

- 2014

- 0406

. Tables 1 and 2 b elow sum m arize the i ssues relevant to this registration review case and the anticipated registration review schedule

.Page 8 of 50

Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Review : 1,3

- PAD

Risk Assessment Assessment Neces sary 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) Yes 1 N/A New None 2
Dietary (drinki ng water) Yes 1 N/A New Yes 1

Occupational Handler Yes 11/7/2007 New Dermal Indoor Exposure Inhalation Indoor Exposure Product Use Occupational Post

Application No N/A None None

Residential Handler No N/A None None

Residential Post Application

- Inci dental Oral and Dermal Yes 8/3/2005 Updated Indoor Residue Product Use Description of Human Activity

Residential Post Application

- Inhalation No N/A None None

Aggregate Yes 1 N/A New None 2

Cumulative No N/A None None

Tolerance Review Yes 1 N/A Ne w N one

Ecological Yes N/A New Down

- the

- Drain Ecotoxicology Environmental F ate (See Table 6)

1 Pending outcome of use profile clarification ( see Section 3.1)

. 2 No residue chemistry data are required at this time. However, additional residue chemistry data may be necessary , if the toxicological point of departure for either the acute or chronic scenario changes during the registration review process. N/A = Not applicable

Table 2

– Anticipated Registration Review Schedule
Anticipate d Activity Target Date * Completion Date Phase 1: Opening the Docket Open Docket and 60

- Day Comment Period for Preli minary Work Plan 2014

- 09 2014

- 09

- 24 Close Public Comment Period 2014

- 11 Phase 2: Case Development

Issue Final Work Plan 2015

- 03

Issue Data Call

- In (DCI) 2016

- 03

Receive Data to be Considered in Risk Assessment 2018

- 03

Open 30

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

- 09

Close Public Comment Period 2019

- 10Page 9 of 50

Phase 3: Registration Review Decision and Implementation
Open 60

- Day Public Comment Period for Pro posed Decision 2020

- 03

Close Public Comment Period 2020

- 05

Issue Final Decision 2020

- 09

Begin Post

- Decision Follow

- up 2020
Total (years) 6

* The anticipated schedule will be revised as ne cessary ( e.g ., need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case).



## 1.2 Case Overview

The docket for 1,3

- PAD ( c ase 5109 ) has been established at http://www. regulations.gov in docket number EPA

- HQ

- OPP

- 2014

- 0406

. 

## 1.3 Chemical Identification and Properties

Table 3 presents the active ingredient to be assessed in case 5109 : 1,3

- Propanediamine,N

- (3

- aminopropyl)

- N

- dodecyl

- (PC Code 067300)

.

Table 3

– Chemical Identification of 1,3

- Propanediamine,N

- (3

- aminopropyl)

- N

- dodecyl

Chemical Name 1,3

- Propanediamine,N

- (3

- aminopropyl)

- N

- dodecyl

Chemical Classification Alkyl Amino Propane

PC Code 067300

CAS N umber 2372

- 82

- 9

Molecular Formula C 18 H 41 N 3 Molecular Weight (grams/mole) 299.543

Molecular Structure

The 1,3

- Propanediamine,N

- (3

- aminopropyl)

- N

- dodecyl

- product chemistry information relevant to risk assessment is summarized in Table 4 , and the details of the product chemistry (Source: MRID Nos. 46332202, 45115304, 45115305, 45115308, 45115309

, 46309706, 45115307, and Lonza MSDS) are discussed in Appendix E

.Page 10 of 50

Table 4

– Physical

- Chemical and Environmenta l Fate Properties for 1,3

- Propanediamine, N

- (3

- aminopropyl)

- N

- dodecyl

Guideline No. Parameter 1,3

- Propanediamine,N

- (3

- aminopropyl)

- N

dodecyl

Physical/Chemical Properties 830.7000 pH 10.6 (1% aqueous solution)

830.7050 UV/Visible Absorption 203.6 nm; 201.6 nm; 218.4 nm; in methanol, acidic methanol and alkaline methanol solutions.
830.7200 Melting point ( o C) Setting point ≥10oC

830.7220 Boiling point ( o C) The boiling point could not be determined due to decomposition of the test substance at approx

. 280oC 830.7300 Density 0.87 g/ml at 20oC
830.7370 Dissociation constant (pKa) pKa values: 9.3 ± 0.104 and 7.15 ±0.054 at 20oC

830.7550 Octanol

- water partition coefficient at 25 o C

(Log K ow ) 1 ,3

- PAD is a polar chemical substance and therefore log Kow is not required.
830.7840 Solubility in water (mg/L) Completely and infinitely soluble in water

830.7860 Solubility in organic solvents Completely miscible at 20oC in Acetone, Ethyl acetate, and Methanol. 830.7950 Vapor pressure (mmHg) 3.3 x 10

- 6 at 25oC

None (calculated) Henry’s law (atm m 3 mol

- 1 )

[VP (mm Hg) * molecular weight (grams/mol)]/[760 * solubility (mg/l)] 1.3 x 10

- 10

atm

- m 3 /mol = atmosphere cubic meter per mole; o C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury



## 1.4 Use/Usage Description

1.4.1 Registrations There are 4 registered 1,3

- PAD products. There are no inert uses and no pending registrations. In addition, EPA Reg. No. 6836

- 284 contains another active ingredient (a.i.), didecyl dimethyl ammonium chloride (DDAC). DDA C will be assessed under a separate registration review case.


### 1.4.2 Summary of Registered Uses

Table 5 presents a summary of the registered uses of 1,3

- PAD that will be assessed in this registration review case

. 1

, 3

- PAD can be applied b y the following application methods: mop, foaming generator, mechanical sprayer, and metering pump.

Table 5

– Summary of 1,3

- PAD Registered Uses

Use Application Method Application Rate Agricultural Premises and Equipment

– Indire ct Food Contact Dairy Farm Premises Poultry Premises Animal Housing Facilities Mop 3.6 ppm Foaming Generator 3.2 ppm Mechanical Sprayer 3.6 ppmPage 11 of 50

Commercial, Industrial, Institutional, Premises and Equipment

Restaurants Mop 3.6 ppm Foaming Gen erator 3.2 ppm Mechanical Sprayer 3.6 ppm Food Handling/Storage Establishments Premises and Equipment

– Indirect Food Contact

Beverage and Food Processing Plants Mop 3.6 ppm Foaming Generator 3.2 ppm Mechanical Sprayer 3.6 ppm

Residential and Pu blic Access Premises

Schools Mop 3.6 ppm Foaming Generator 3.2 ppm Mechanical Sprayer 3.6 ppm

Bars and Cafeterias Mop 3.6 ppm Foaming Generator 3.2 ppm Mechanical Sprayer 3.6 ppm

Athletic Facilities Mop 3.6 ppm Foaming Generator 3.2 ppm

Mec hanical Sprayer 3.6 ppm Medical/Dental/Veterinary Premises and Equipment

Pet Shops Mop 3.6 ppm Foaming Generator 3.2 ppm Mechanical Sprayer 3.6 ppm

Preservatives Metalworking Fluids (Enclosed) Metering Pump 2500 ppm Oil Field Flood Water Systems Metering Pump 20 ppm



### 1.4.3 Usage Information

No usage information is available in the Kline Biocides Report for 1,3

- PAD.



## 1.5 Regulatory Histor y

A Reregistration Eligibility Decision (RED) was not completed for 1,3

- PAD because it was registered after November 1, 1 984.



### 1.5.1 Tolerance Information For the active ingredient 1,3

- PAD

, 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) Sect ion 408. The US Food and Drug Administration (US FDA) has not established any food contact notifications or food additive regulations under FFDCA Section 409 for 1,3

- PAD.Page 12 of 50

The a gency anticipates reviewing the potential need for tolerances/exemptions during the registration review process.



## 1.6 Incidents

1.6.1 Human Health

No 1,3

- PAD human poisoning incidents have been reported in OPP’s Incident Data System (IDS) for the time period spanning 2005 to 2013 based on the search conducted on August 25, 2014

.


### 1.6.2 Ecological

Ther e are n o ecological incidents in IDS as of March 5, 2014.


## 2 A nticipated Data Needs

Table 6 presents a summary of the data anticipated as being needed to support this registration review.Docket Number EPA

- HQ

- OPP

- 2014

- 0406

www.regulations.gov

Page 13 of 50 Table 6

– Studies Anticipated as Needed for the Registration Review of 1,3

- PAD

GLN Study Name Test Substance Time Frame

(Measured in months from DCI Receipt) Risk Assessment(s) Data

Will Support Use Site(s) Triggering

Anticipated Data Requirement Applicable Ex posure Scenario

835.1230 Leaching

- adsorption

- desorption TGAI 12 Environmental exposure All Ecological and drinking water exposure 835.3110 1 ,2 835.3220 835.3240 835.3280 Ready biodegradability or one of

three biodegradation in activated sludge simulation tests TGAI 12 Environmental exposure All Ecological and drinking water exposure

850.3300 or OECD 209 2 Activated sludge respiration

inhibition TGAI 12 Toxicity to WWTP organisms All Ecological and drinking water exposure

835.4100 Aerobic soil metabolism T GAI 24 Environmental exposure All Ecological and drinking water exposure

835.4300 Aerobic aquatic metabolism TGAI 24 Environmental exposure All Ecological and drinking water exposure

835.4400 Anaerobic aquatic metabolism TGAI 24 Environmental exposure Al l Ecological and drinking water exposure 850.4500 Algal toxicity Tier II, green algae TGAI 12 Aquatic plants All Down

- the

- drain

850.4500 Algal toxicity Tier II, freshwater and

saltwater diatoms 3 TGAI 12 Aquatic plants All Down

- the

- drain

850.4550 Cyanoba cteria 3 Tier II TGAI 12 Aquatic plants All Down

- the

- drain

850.5400 Aquatic plant toxicity, Lemna sp. 3 TGAI 12 Aquatic organisms All Down

- the

- drain

850.1075 Estuarine/marine fish, acute toxicity TGAI 12

- 18 Saltwater fish All Down

- the

- drain
850.1025

or 8 50.1055 Oyster, shell deposition

or Bivalve embryo larval toxicity TGAI 12 Saltwater organisms All Down

- the

- drain

850.1035 Mysid, acute toxicity TGAI 12 Saltwater organisms All Down

- the

- drain

850.1400 Fish, early life stage 4 TGAI 12 Aquatic organisms All Down

- the

- drain

850.1300 Aquatic invertebrate, life cycle 4 TGAI 12 Aquatic organisms All Down

- the

- drain

870.3465 90

- Day Inhalation Toxicity TGAI 12 Occupational handlers Hard surface disinfectant and sanitizer Mopping ; sprayer; foamingPage 14 of 50

GLN Study Name Test Substance Time Frame

(Measured in months from DCI Receipt) Risk Assessment(s) Data

Will Support Use Site(s) Triggering

Anticipated Data Requirement Applicable Ex posure Scenario

870.3700 Prenatal Developmental Toxicity

Study in non

- rodents TGAI 12 Occupational handlers; residential post

application All Human health exposure

875.1200 Dermal Indoor Exposure TEP 12

- 24 Occupational Handler All (except metalworking and oil fields) Mopping; sprayer; fo aming

875.1400 Inhalation Indoor Exposure TEP 24 Occupational Handler All (except metalworking and oil fields) Mopping; sprayer; foaming

875.1700 Product Use TEP 12 Occupational Handler All Mopping; sprayer; foaming

875.2300 Indoor Residue TEP 24 Reside ntial Post Application

- Incidental Oral and Dermal Disinfectant Use on Floors Dermal and Incidental Ingestion Post A pplication exposure

875.2700 Product Use TEP 12 Residential Post Application

- Incidental Oral and Dermal All Dermal and Incidental Inges tion Post A pplication exposure

875.2800 Description of Human Activity TEP 12

- 14 Residential Post Application

- Incidental Oral and Dermal Disinfectant Use on Floors Dermal and Incidental Ingestion; Post

application exposure

1 The n eed for these biodegr adation stud ies will be based on results of an Activated Sludge Respiration Inhibition test.

2 EPA published draft guidance under guideline 850.6800 and has since published final guidance for this study under guideline 8 50.3300: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0021 . OECD Test Guideline 209 can also be used as guidance for this study, available online at http://www.oecd

- ilibrary.org/content/book/9789264070080

- en . The results of the Activated Sludge Respiration Inhibition Test (ASRI) will determine which of these four biodegradation tests would be required. 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 would be required. If the ASRI te st EC50 is greater than 20 mg/L, then the registrant would be required to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test

- Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be required. If, however, the antimicrobial fails the Ready Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test

- Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study would be required.

3 Data for freshwater and marine diatoms and cyanobacteria would be needed only if the EC50 for the green algae is less than 1 ppm

. 4 E ither freshwater or e stuarine/marine, depending on which was most acutely sensitive

.Docket Number EPA

- HQ

- OPP

- 2014

- 0406

www.regulations.gov

Page 15 of 50 

## 3 Human Health Risk Assessment

The a gency anticipates the need to conduct a human health risk assessment for 1,3

- PAD

. Additionally, t he a gency anticipates the need to require additional data for the currently registered use s, such as a 90

- day inhalation toxicity study and a developmental toxicity study in

non

- rodents

, and all applicable exposure studies when conducting the registration review (as noted in Table 6 )

. 

## 3.1 Exist ing Toxicological Endpoints

The a gency anticipates the need to revise the existing toxicological endpoints , shown in Table 7

, as part of this registration review. All available information

, including existing toxicology studies an d valid scientific literature, will be considered in establishing the endpoints to be used in the registration review risk assessment. A dditional studies

, such as a 90

- day inhalation toxicity study and developmental toxicity study in non

- rodents are antici pated to be required for risk
assessment based on the adverse effects observed in the oral studies and the currently registered

uses

. A detailed description of the available toxicity studies is provided in Appendix A

Table 7

– Existing Toxicological Endpoints for 1,3

- PAD

Exposure Scenario Dose Used

in Risk Assessment (mg a.i. /kg/day) Target Margin of Exposure (MOE), Uncertainty Factor (UF), FQPA Safety Factor (SF) Study and Toxicologica l Effects

Occupational/Residential ( Non

- Dietary ) Risk Assessments
Incidental Oral

Short

- Term (1

- 30days) and Intermediate

- Term (30 days

- 6 months) NOAEL maternal = 7.6 MOE = 100 ( 10X interspecies, 10X intraspecies ) Developmental/Rat (MRID 451519 03 )

LO AEL= 22.7 mg a.i. /kg/day

, based on clinical signs, decreased mean body weight gain and mean food consumption
Dermal

All routes LOAEL =1. 5 (LDT) MOE = 300 ( 10X interspecies, 10X intraspecies , 3X for using a LOAEL value ) 90 Day Subchronic Dermal/ Rat ( 45151 902 )

NOAEL: not established LOAEL=1.5 mg a.i./kg/day (LDT), based on dermal erythema and edema observed in male and female rats. Sternal bone marrow hyperplasia in female rats



## 3.2 Dietary Exposure

The a gency has not previously conducted a dietary (food and d rinking water) exposure and risk assessment for 1,3

- PAD

. Uses of 1,3

- PAD that may r esult in dietary (food) exposure include hard surface disinfectant applications in hotels, motels, schools, bars and cafeterias, and convenience stores. However, the agency is working with the registrants because current labels are unclear as to which of these applications are intended for food

- contact surfaces. If currentPage 16 of 50

labels are amended to restrict applications to non

- food contact areas only, no dietary (food) exposure i s expected. However, if the intended use pattern is for food

- contact surfaces and the

curre nt labels are not amended, the a gency would need to conduct a revised dietary (food and drinking water) exposure and risk assessment.

With respect to drinking water exposure, several approved uses ( disinfectants and sanitizers, metalworking fluids, oil recovery water systems, and storage ponds for oilfield uses) may result in 1,3

- PAD being discharg ed into waste water and subsequently running off into surface water.



### 3.2.1 Fo od

The a gency anticipates the need to conduct dietary exposure assessments as part of the registration review process since none have been previously conducted. Current uses as hard surface disinfectants in multiple settings may result in dietary (food) ex posure. Initially, a screening

- level analysis will be conducted once toxicological points of departure are selected. Residue chemistry data are not anticipated to be required at this time. The dietary exposure contribution will be considered in the aggreg ate assessments conducted during registration review. If the toxicological point of departure (PoD) for either the acute or chronic scenario changes during the registration review process, additional residue chemistry data may be required.

If current label s are amended during registration review to limit the use pattern to non

- food contact areas only, no dietary (food) exposure would be expected and no dietary exposure and risk assessment will be necessary

.


### 3.2.2 Drinking Water A drinking water assessment has not been conducted for 1,3

- PAD in the past. Howe ver, for several approved uses ( disinfectants and sanitizers, metalworking fluids, oil recovery water systems, and storage ponds for oilfield uses ) the a gency cannot rule out the potential for 1,3

- PAD to enter d rinking water. There are uncertainties with respect to the residues of concern in drinking water, the magnitude of these potential residues, their mammalian toxicities, how persistent they will be, and if they are likely to pass through a wastewater treatm ent plant (WW TP). Therefore, the a gency anticipates needing certain environmental fate data listed in Section 4 of this PWP. These data will be useful to determine whether, and to what extent, residues of 1,3

- PAD pass through a W WTP. The a gency anticipates using these data and/or other sources of information during the risk assessment stage of registration review to determine the potential for discharged residues of 1,3

- PAD to result in human dietary exposure via drinking water, which may trigger a drinking water assessment. No residue chemistry data are expected to be needed at this time to characterize residues of 1,3

- PAD in drinking water.



## 3.3 Occupational and Residential Exposures

The a gency anticipates the need to develop a new occupational and residential exposure (ORE)
assessment during the registration review process . The ORE assessment will need to be revised to account for new ORE methodologies and to utilize the exposure data that are anticipated to be required for registration review.Page 17 of 50



### 3.3.1 Occupa tional Handler Exposure Occupational handler exposures for the mopping, low pressure spray and wipe scenarios were assessed for registration in 2005 (US EPA, 2005). The resulting margin s of exposure ( MOE ) s in 2005 ranged from 308

- 815 for low pressure spray and mop, which are greater than the target dermal MOE of 300. The resulting MOEs for the wiping scenario were less than the target dermal MOE of 300. However, the wiping use is not currently found on the ex isting registered labels. The a gency anticipates the need to reassess the current occupational application scenarios (mopping, foaming generator, and mechanical sprayer) and anticipates the need for new dermal and inhalation exposure studies.

Occupational handler exposures for enclosed metalworking flui ds and oil field flood water systems were assessed in 2007 (U.S. EPA 2007 ). EPA expects dermal and inhalation exposures to be minimal based on engineering controls and existing labeling. Due to the fact that 1,3

- PAD is used in closed systems for metalworki ng fluids and oil field uses, has a low vapor pressure (10

- 6 ), and possesses a half

- life of 0.7 hours ; inhalation exposures are not expected. Thus, EPA anticipate s that there are no dermal and inhalation risks for 1,3

- PAD ; and therefore these exposures wi ll not be quantitatively evaluated for these two uses

. The occupational handler scenarios as listed in Table 8 will need to be assessed during registration review.

Table 8

– Occupational Handler Exposu re Scenarios for 1,3

- PAD

Scenario Exposure Route(s) Duration
1. Mopping Floors With Disinfectant Cleaners in Industrial, Commercial and Institutional Facilities Dermal

, Inhalation Short and Intermediate Term
2. Mechanical Sprayer Application of Disinfec tant Cleaners in Industrial, Commercial and Institutional Facilities Dermal

, Inhalation Short and Intermediate Term
3. Foaming Generator Sprayer Application in Industrial, Commercial and Institutional Facilities Dermal

, Inhalation Short and Intermedia te Term



### 3.3.2 Occupational Post

- application No occupational post

- application exposures are expected based on engineering controls and existing label language

.


### 3.3.3 Residential Handler Exposures
All 1,3

- PAD labels indicate products are only for instituti onal, industrial, and commercial use. Therefore, resid enti al handler exposure is not expected.



### 3.3.4 Residential Post

- Application Exposures EPA anticipates the need to revise the residential post

- application assessment conducted in support of the 2005 ORE

. Residential post

- application exposures could result when bystanders (adults and children) come in contact with 1,3

- PAD in areas where pesticide end

- use productsPage 18 of 50

have recently been applied (e.g., treated hard surfaces/floors), or when children incidentally ingest the pesticide residues through hand

- to

- mouth activities when playing on treated floors

.

The MOE s were not of concern for hard surface disinfection of floors

, but they were calculated using an assumption of solution coverage (1000 square feet per ga llon) that will have to be reassessed using updated exposure algorithms . The dermal MOE of 312 for treated floors was slightly over the target MOE of 300 . The quantitative exposure/risk assessment to be developed for residential handlers will be based on t he following scenarios presented in Table 9

.

Table 9

- Residential Post

- Application Exposure Scenarios for 1,3

- PAD

Scenario Exposure Route(s) Duration Residential Exposures Post application exposure t o floors cleaned with disinfectant cleaning solutions

. Dermal Incidental Oral Short and Intermediate Term



## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures

The a gency anticipates the need to conduct the aggregate assessment. Upon a reevaluation an d selection of toxicological endpoints, combined with the human health exposure assessments expected as a part of this registration review case, aggregate exposures will need to be assessed. This assessment will include dietary (food) exposures and residen tial exposures.



### 3.4.2 Cumulative Exposures With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a

common mechanism of toxicity finding as to 1,3

- PAD and any other substances and 1,3

- PAD does not appear to produce a toxic metabolite produced by other substances. For the purposes of this registration review, therefore, EPA has not assumed that 1,3

- PAD 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 has not previously conducted a risk assessment that supports a complete endangered species determination for 1,3

- PAD when used in metalworking fluids at 500

- 2,500 mg/l (ppm) and non

- marine/n on

- estuarine oil field water flood systems at 5

- 20 ppm. The ecological risk assessment planned during registration review will allow the agency to determine potential acute and chronic risks to aquatic organisms exposed to 1,3

- PAD that may be transported f rom treatment sites into the aquatic environment

. Such sites include metalworking fluids that enter wastewater treatment plants (WWTPs) and oil field water flood systems that have the potential to enter surface water through WWTP effluent or overflow from storage ponds and ground water from un

- cased wells or from leaching in unlined storage ponds

. Sites also includePage 19 of 50

sanitizer/disinfectants applied to hard surfaces and subsequently discharged down

- the

- drain from rinsing of mops/cloths used to wipe sanitizer/ disinfectant from hard surfaces. The risk assessment also will allow the agency to determine whether each use of 1,3

- PAD has 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical habitat s. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriat e.

Based on the antimicrobial uses of 1,3

- PAD with active products in Table 5, the agency has created conceptual m odels for potential routes of environmental exposure which are included in “Conceptual Models for Environmental Exposure Pathways of Antimicro bial Pesticides”, found in the docket at www.regulations.gov (EPA

- HQ

- OPP

- 2014

- 0 638

- 001 ) . For particular 1,3

- PAD

uses , the relevant page numbers are 15 ( down

- the

- drain exposure from use of sanitizer/disinfectant at beverage and food processing plants, bars, schools, and cafeterias ), 18 ( metalworking fluids ), and 19

- 22 (oilfield flood water systems) . All relevant routes of environmental exposure will be considered in the risk assessment.



## 4.1 Environmental Fate Assessment

Based on the chemical and physical properties, 1,3

- PAD is miscible in water and is unlikely to move from soil or water into air based on the vapor pressure of 3.3 x 10

- 6 mm Hg and the Henry’s Law constant of 1.3 x 10

- 10 atm m 3 mol

- 1 (Table 4). 1,3

- PAD is stable to both hydrolysis (MRID 45115327) and to photodegradation in water (Table 4) but no data have been submitted for biological degradation, sorption, or toxicity to WWTP microorganisms. As a result, the

a gency cannot determine the potential for 1,3

- PA D to reach or persist in the aquatic environment and therefore additional aquatic data will be needed

.


### 4.1.1 Water Quality
1,3

- PAD is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 1

. In addition, no t otal m aximum d aily l oads (TMDL) have been developed for 1,3

- PAD 2

. More information on impaired water bodies and TMDLs can be found at EPA’s website 3

. 

## 4.2 Environmental Exposure Pathways

There are potential pathways by which 1,3

- PAD and potenti al degradates can reach the aquatic environment. One pathway is by use of 1,3

- PAD in metalworking fluids that enter wastewater treatment plants (WWTPs) and subsequently surface water. Other pathways associated with the use of 1,3

- PAD in oil field water flo od systems include: discharge via WWTP effluent to surface water; overflow from storage ponds to surface water; and leaching to ground water from uncased

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

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

3 http://www.epa.gov/owow/tmdl/Page 20 of 50

wells or unlined storage ponds. Another pathway is by use of 1,3

- PAD as a hard surface sanitizer/disin fectant which is wiped by mop and/or cloth and then rinsed down

- the

- drain to domestic wastewater treatment plants and subsequently to surface water.



### 4.2.1 Ecological Effects Assessment Acute and chronic toxicity data from registrant

- submitted studies (850 OCSPP Harmonized Test Guidelines) are used to evaluate the potential effects of 1,3

- PAD to plants and animals

. All available ecotoxicity endpoints are tabulated in Appendix C. The agency uses the most sensitive of these endpoints for assessing risks. The endpoin ts selected for 1,3

- PAD are provided in Table 10

.

Table 10

– Ecological Effects Endpoints

Receptor Group Test

Material Risk

Scenario Toxicity Endpoint Reference

Freshwater fish TGAI Acute LC 50 = 0.45 m g ai/L 451153 12
Chronic Data gap

--

Freshwater invertebrates TGAI Acute EC 50 = 0.073 m g ai/L 45115313

Chronic Data gap

--

Estuarine/marine fish TGAI Acute Data gap

-- Chronic Data gap

--
Estuarine/marine invertebrates TGAI Acute Data gap

-- Chronic Data gap

--
Algae TGAI EC 50 and NOAE C Data gap

--

Aquatic plants

, vascular TGAI EC 50 and NOAE C Data gap

--

Birds TGAI Acute LD 50 = 25 mg ai/kg 451153

- 10



### 4.2.2 Mechanism of Action

The agency has no information on the mechanism of action for 1,3

- PAD for terrestrial and aquatic invertebrates

. 

## 4.3 Exposure Analysis Plan

4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates

Available OPP models will be used to determine the estimated environmental concentration (EECs) in the aquatic environment. The Down

- t he

- Drain module of E

- FAST will be used to assess potential exposures to aquatic organisms from discharges of sanitizer/disinfectant to domestic WWTPs then subsequently to surface water. The General Population and Ecological Exposure from industrial release s module of E

- FAST will be used to assess potential exposures to aquatic organisms from use of 1,3

- PAD that is used in metalworking fluids and oil recoveryPage 21 of 50

water systems and discharged to WWTPs, then subsequently to surface water. For the potential surface and ground water exposure from storage ponds for the oilfield uses, the best available assessment tools, including models or available monitoring data, will be considered. Resulting exposure estimates will be compared to the toxicity endpoints to determin e if levels of concern are exceeded for each receptor group.



### 4.3.2 Screening Level Down

- the

- Drain Analysis There are two types of down

- the

- drain releases for 1,3

- PAD: those from industrial uses (i.e, metalworking fluids and oil recovery water systems) that go t o industrial wastewater treatment plants and subsequently surface water and those from hard surface sanitizer/disinfectant uses that are expected to go primarily to domestic wastewater treatment plants and subsequently to surface
water. A screening level d own

- the

- drain assessment is used to determine potential upper bound exposures and risks to aquatic organisms from uses that are expected to result in discharges to domestic wastewater treatment plants and subsequently to surface water. When information on production volume is available, a screening

- level down

- the

- drain analysis can be used to demonstrate negligible potential for exposure and risk to aquatic organisms and lead to the conclusion that specific environmental fate and ecotoxicity data would not be required.

P roduction volume data are not the only information needed to determine potential exposures to aquatic organisms from industrial uses that can enter surface water via WWTPs. The down

- the

drain module of E

- FAST is not appropriate for estimating potential exposures to aquatic organisms from industrial uses that could result in releases to surface water via WWTPs

. To estimate potential exposures from industrial uses, one must use the General Population and Ecological Exposure from Industrial Relea ses module of E

- FAST. The use of this module requires additional input data that are not available and is beyond the scope of this preliminary risk assessment. Environmental fate and ecotoxicity data requirement s that would be needed to perform a risk ass essment for industrial uses are expected to be included in the generic data call

in (GDCI) based on the absence of this information.

A screening level down

- the

- drain analysis will not be performed as part of this preliminary risk
assessment since uses of 1 ,3

- PAD are not limited to those that would result in releases to surface water via domest ic wastewater treatment plants but also include industrial uses that can reach surface water via WWTPs

. Consequently, a screening

- level down

- the

- drain assessment would not provide information on potential exposure to aquatic organisms from indirect and direct releases to surface water as a result of industrial uses.



## 4.4 Effects Analysis Plan

The agency will use acute and chronic toxicity data from studies submitted by the registrant (See Table 10). Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will be searched during the risk assessment phase of 1,3

- PAD and the data reviewed following the agency ’s policy for reviewing public literaturePage 22 of 50

for use in assessing risks from pesticides 4

. Those ecotoxicity values found in the public literature to be more sensitive than those currently in Table 10 and those which satisfy an existi ng data gap(s) will be used during the risk assessment phase of 1,3

- PAD to update Table 10 . ECOTOX was created and is maintained by the USEPA, Office of Research and Development, and the National Health and Environmental Effects R esearch Laboratory's Mid

- Continent Ecology Division.


## 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 incl ude 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 e ffects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studie s that assess growth, developmental and reproductive effects in different taxonomic groups. A s required by FFDCA section 408(p ), 1,3

- PAD is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyr oid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a dose

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

Under FFDCA secti on 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 li st of chemicals identified for EDSP screening was published on June 14, 2013 5 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine dis ruptors.

4 http://www.epa.gov/pesticides/science/efed/policy_guidan ce/team_authors/endangered_species_reregistration_work group/esa_evaluation_open_literature.htm

5 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 200 9

- 0477

- 0074 for the final second list of chemicals.Page 23 of 50

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. 6



## 6 Optional Label Changes

The agency invites comm ent on any label amendments that could be considered to eliminate the anticipated need for EPA to require certain data, reduce the possibility that EPA’s planned risk assessments overestimate risk due to reliance on conservative assumptions, and/or improve label clarity.

It is recommended that all labels and uses be clarified as to whether or not they are intended for food or nonfood contact.


## 7 Guidance for Commenters

7.1 Preliminary Work Plan
The public is invited to comment on EPA’s Preliminary Work Plan and r ationale. The agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work plan for the 1,3

- PAD registration review case.



### 7.1.1 Trade Irritants Through the registration revie w process, the agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may

mo dify tolerance levels to do so, when possible. Stakeholders are asked to comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regar ding the nature of the concern.



### 7.1.2 Water Quality

The agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of I mpaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 7 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.



### 7.1.3 Environmental Justice

EPA seeks to achi eve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help add ress potential

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

7 http://www.epa.gov/oppsrrd1/registration_review /water_quality_sop.htmPage 24 of 50

environmental justice issues, the agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to 1,3

- PAD compared t o the general population. Please comment if you are aware of any sub

- populations that may have atypical, unusually high exposure compared to the general population.



### 7.1.4 Structure Activity Relationships EPA must rely upon information of appropriate quality and reliability for each decision made by the agency . In the OPP, the evaluation process for a pesticide chemical traditionally begins with the applicant’s submission of a set of studies conducted with the specific pesticide chemical of interest. The use of t he results of such testing (measured data) is a logical, scientifically rigorous process that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in v arious animal species.

Today, there is significant interest in alternative techniques, i.e., techniques other than data generation that could significantly inform the agency ’s decision

- making process. Recently, OPP has made increasing use of structure act ivity relationship (SAR) as part of its regulatory decision

- making process. In the SAR process, a chemical's molecular structure is compared to that of other chemicals for which data are available. These structural similarities are then used to make predic tive judgments about a chemical’s physical, chemical, and biological properties. Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a selected set of measured data on a single physical, chemical, or biological property is used to derive a model (an equation) to predict the value of that property.

Since SAR assessments and QSAR modeling are another set of tools that are available to agency scientists, OPP has begun a process shift that envisions shifting from the current study

- by

- study approach to an approach in which the use of predicted data, generated using validated models, is considered along with inf ormation from open literature and studies specifically generated under Part 161 requirements. All relevant information would be considered as part of a weight

- of

- the

evidence evaluation.

At this time, EPA believes that for certain endpoints, especially ph ysical/chemical and fate properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals. When considering biological properties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is appropriate because the risk assessment for lower toxicity chemicals can be stream

- lined, i.e., a screening

- level a ssessment procedure rather than multiple tiers of assessments with progressively more data requirements.

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the 1,3

- PAD ca se, then the agency invites submission o f this information. The submitter would be expected to supply a rationale describing the utility of the information and provide documentation on the scientific validity of the information. The determination that the predicted data fulfills the data require ment would be at the sole discretion of the agency . Pre

- submission consultation with the agency is encouraged.Page 25 of 50



### 7.1.5 Additional Information

Stakeholders are also specifically asked to provide available information and data that will assist the agency in refini ng its risk assessments, including any species

- specific ecological effects determinations. The agency is interested in receiving the following information:

1. Confirmation on the following label information: A. Sites of application B. Formulations C. Application m ethods and equipment D. Maximum application rates E. Frequency of application, application intervals and maximum number of applications F. Geographic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non

- agricultural u ses (e.g., materials preservation) 5. Typical application interval 6. State or local use restrictions 7. Ecological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the agency 8. Monitoring data



## 8 Next Steps

After the 60

- day comment period closes in November, 2014 , the agency will review and respond to any comments received in a timely manner, and then issue a Final Work Plan for the 1,3

- PAD

case.Page 26 of 50



## 9 References

45115304 Sloan, R. (1999) Lonza bac 12

- Physical and Chemical Properties: Lab Project

Number: SP

- 99043

- A. Unpublished study prepared by Lonza, Inc. 30 p. {OPPTS 830.6315, 830.7000, 830.7050, 830.7100, 830.7300}

45115305 Sarff, P.; Edgar, L. (1999) Boiling Point Determination of Lonzabac 12: Lab

Project Number: SP

- 99005

- A: 45066. Unpublished study prepared by ABC Laboratories, Inc. 14 p. {OPPTS 830.7220}

45115307 Sloan, R. (1999) Lonzabac 12

- Stability to Normal and Elevated Temperatures,

Metals and Metal Ions: Lab Project Number: SP

- 9901 0

- A. Unpublished study prepared by Lonza Inc. 24 p. {OPPTS 830.6313}

45115308 Lonza, Inc.; Lewis and Harrison, LLC. (2000) Product Chemistry: Discussion of

Physical and Chemical Properties: Lonzabac 12. Unpublished study. 7 p. {OPPTS 830.6304, 830.6317, 830.6320}

45115309 Lonza, Inc.; Lewis and Harrison, LLC. (2000) Product Chemistry: Vapor Pressure

for Lonzabac 12. Unpublished study. 8 p. {OPPTS 830.7950}

46309706 Sarff, P. (1999) Corrosion Characteristics of Lonzabac 12. Project Number: 45065,

SP/9900 4/A. Unpublished study prepared by ABC Laboratories, Inc. 15 p.

46332202 Sloan, R. (2000) Procedure for Determining Dodecylamine Content in Lonzaback

12. Unpublished study prepared by Lonza, Inc. 5 p.

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

Database System. Version 3.0. Available: http://www.epa.gov/ecotox/Page 27 of 50 

# Appendix A T oxicology Profile

Acute Toxicity for Product Labeling

As listed in Table 12 , 1,3

- P A D was found to be low toxic for both acute oral and dermal toxicity (To xicity Category III) but moderate toxic for acute inhalation toxicity (Toxicity Category II)

. It was shown to be mildly irritating to irritating the e ye s ( Toxicity Category II

- I I I) but corrosive/

s ever ely irritating to skin (Toxicity Category I). 1,3

- PAD i s a dermal sensitizer.

Table 11

– Acute Toxicity Studies for 1,3

- PAD

Guideline No. /Study Type MRID No. Results Toxicity Category 870.1100 Acute oral toxicity

– rat 45115314 LD 50 = 933 mg/kg (♂); LD 50 = 812 mg/kg (♀); LD 50 = 871 m g/kg (combined) III

870.1200 Acute dermal toxicity

– rat 45115315 LD 50 > 2000 mg/kg III

46603601 LD 50 > 200 mg/kg (Limit Test) II

870.1300/ Acute inhalation toxicity

– rat 46603603 L C 50 > 0.052 mg/ L (Limit Test) II 47272201 L C 50 > 0.053 mg/ L (Limi t Test) II 48980409 0.62 mg/ L < L C 50 < 2.0 mg/ L (Limit Test) III
870.2400/ Acute eye irritation 48980413 Slightly irritating III 48980414 Irritating II 870.2500/ Acute dermal irritation

– rabbit 4511531 6/7; 45445316 Sever/c orrosive skin irritant I

870.2600/ Dermal sensitization

– g uinea p ig 4511531 8 No a skin sensitizer N/A 46603602 A skin sensitizer N/A 48980410 A skin sensitizer N/A N/A=Not applicable 

## Subchronic Toxicity

Adequacy of Database for Subchronic Toxicity: The database for su bchronic toxicity is considered incomplete. A 90

- day oral toxicity study in the rat (MRID 45151901) and a 90

- day dermal toxicity/immunotoxicity study (MRID 45151902) are available for addressing subchronic toxicity. A route

- specific 90

- day inhalation toxic ity study in rats is anticipated to be required based on the pulmonary effects observed in the oral studies and the currently registered use s such as a hard surface disinfectant with “coarse mechanical sprayer” (EPA Reg. No. 6836

- 284) in the registration r eview risk assessment

.
870.3100 90

- Day (13

- Week) Oral Toxicity

– Rat

(1) In a subchronic range

- finding toxicity study (MRID 45115319), 1,3

- PAD (unknown purity) was administered daily to Wistar rats (5/sex group), via oral gavage at dose levels of 10, 60, 3 60 and 500 mg/kg

- day for a period of 28 days.Page 28 of 50

Clinical observations of salivation, respiratory sound, gasping for breath, and slight piloerection were noted in rats at 360 and 500 mg/kg

- day. Slight piloerection was also noted in individual animals at 10 and 60 mg/kg

- day. There were pre

- terminal deaths in both sexes of rats at 360 (3 male, 4 female) and 500 (4 male, 4 female) mg/kg

- day. Macroscopic changes (reduced organ size of spleen, accessory genital glands and organs, thymus) were noted in rats at  36 0 mg/kg

day. Microscopic evidence of submucosal and mucosa gastritis and glandular epithelial degeneration were found in rats at 60 mg/kg

- day.

The no observed effect level (NOAEL) , determined by the study authors, was 10 mg/kg

- day based on the absence of macroscopic and microscopic treatment

- related findings that were reported at higher doses. The lowest observed effect level (LOAEL) is 60 mg/kg/day.

This study is classified as Unacceptable . There is omission of data supporting the preparation, stability, homogeneity and concentration of the dosing formulation. There are no guideline requirements for this type of study.

(2) In a subchronic toxicity study (MRID 45151901), 1,3

- PAD (purity of 29.8% a.i. ) suspended in purified water was administered to Albino W istar Crl:(Wi)Br rats (10/sex/dose) by oral gavage at dose levels of 0, 5 (1.5 mg a.i.), 10 (3.0 mg a.i.), 30 (8.9 mg a.i.) or 90 (26.8 mg a.i.) mg/kg/day for 90 consecutive days. Additional groups of rats (10/sex/dose) were treated at doses of 0 or 90 (26 .8 mg a.i.) mg/kg/day for 90 days and sacrificed after a 28

- day recovery period.

Five animals from the 90 (26.8 mg a.i.) mg/kg/day group were sacrificed prematurely due to morbidity as a result of dosing complications causing esophageal perforation and ple ural gavage. Clinical signs of toxicity observed in treated animals included: salivation and hyperactivity in the two high

- dose groups and reduced righting reflex in the high

- dose ( 90 mg/kg/day ) males and in all females except the low

- dose group

.

D ecreased mean body weight gains for both males and females in the two high

- dose groups were observed over Weeks 6

- 13 and over Weeks 0

- 13 for the high est

- dose group. Mean body weight gains were similar to the control group during the recovery period (week 13

- 17).

Significantly decreased mean food consumption was reported in the highest

- dose males throughout the study including the recovery period and in females of the same dose group at 7

- 13 weeks only.

Significant differences in hematology parameters were not cons idered toxicologically or biologically relevant since the levels were within normal ranges for Wistar rats. Significant dose

related increases of aspartate aminotransferase (AST) enzymes were reported in both sexes from the two high

- dose groups at Week 13; alanine aminotransferase (ALT) enzymes were significantly increased in the highest

- dose males at Week 13. At the end of the recovery period, AST values remained statistically elevated, although ALT values normalized. The biological importance of these cha nges is uncertain.

At terminal necropsy, both sexes surviving until the conclusion of the treatment period exhibited macroscopic changes in the small intestine (primary the jejunum) which are correlated withPage 29 of 50

histopathological assessments of an increased number of macrophages in the jejunum of the two high

- dose groups . Macrophages persisted in the recovery animals of the highest

- dose group

. Nephrotoxicity effects , presented as moderate proximal tubular changes in males and minimal changes in females, was observed in the highest

- dose group . In the recovery period , minimal proximal tubular changes were noted in males and m inor basophilic changes in the female. These changes were correlated with an increase in the relative organ weight.

Nasopharyngeal mucosa changes were noted in all treatment groups except for the lowest

- dose
group

. These changes persisted into recovery at the highest

- dose level . The lungs at the highest

dose level also showed changes but didn’t persist into recovery.

An increased number of macrophages were also noted in the mesenteric lymph nodes of the two high

- dose group animals of both sexes. These changes persisted into the recovery phase at these dose levels.

Based on these findings, the NOAEL 5 (1.5 mg a.i.) mg/kg/day is for systemic toxicity. The LOAEL is 10 (3.0 mg a.i) mg/kg/day and is based on the clinical finding of a reduced righting reflex.

This toxicity study is classified as Acceptable and fulfills the guideline requirements of OPPTS 870.3100 for a s ubchronic o ral t oxicity s t udy.

(3) A histopathology review (MRID 45115320) was conducted to verify the reported toxicity of 1,3

- PAD . In a 90

- day o ral toxicity study (MRID 451519 01), 1,3

- PAD was administered by oral gavage to Albino Wistar Crl:(Wi)Br rats (10/sex/dose) at dose level s of 0, 5 (1.5 mg a.i.), 10 (3.0 mg a.i.), 30 (8.9 mg a.i.), or 90 (26.8 mg a.i.) mg/kg for 90 consecutive days (Groups I

- V, respectively), An additional group (10 rats/sex) was treated at doses of 0 or 90 (26.8 mg a.i.) for 90 days and sacrificed after a 28

- day recovery period. Macro scopic and microscopic examinations were performed

. Histopathological changes were reported in the jejunum, mesenteric lymph nodes, skeletal muscle, kidneys, glandular stomach and nasopharyngeal

mucosa.
The pathological eval uation below has been included in the 90

- day o ral toxicity study (MRID 451519 01).

A re

- evaluation of the original tissue samples were conducted by an independent histopathologist (slides were obtained from Lonza). Severity of tissue insult was scored on a five point scale. For all non

- neoplastic lesions in bilateral paired organs, the severity score of the worst affected organ was recorded. There were no significant differences between the two assessments and similar results were observed in the kidneys, n asopharyngeal mucosa, lungs

, liver, small intestine, and mesenteric lymph nodes. The conclusions, however, regarding the renal findings were not in total agreement with the original assessment.

Upon re

- evaluation of the renal tissues, the review pathologi st noted that:

(i) The renal changes were indicative of nephrotoxicity, rather than an exacerbation of a spontaneous change, and presented moderate proximal tubular changes characterized byPage 30 of 50

multifocal dilation and basophilia with evidence of degeneration, regeneration and hyperplasia in Group V males. Proximal tubular changes noted in Group V females were similar, but of lesser severity. Group V recovery males demonstrated interstitial fibrosis while females demonstrated only minor basophilic changes. These changes indicated a nephrotoxic effect of the test compound.

(ii) In the re

- evaluation the stomach lesions, all changes were considered to be artifacts and not treatment related.

(iii) The respiratory findings were also not completely characterized in t he original report. The reviewer observed muco

- purulent exudate in the respiratory tract indicative of a pneumonitis, likely due to the inhalation of the copious nasal mucus exudate. The elevated serum AST levels observed were also a possible result of the soft tissue damage of the nasopharynx.

The pathology reviewer concluded that the NOAEL was 30 (8.9 mg a.i.) mg/kg/day (for systemic toxicity) and was based on the histopathological re

- evaluation. The LOAEL was 90 (26.8 mg a.i.) mg/kg/day and was based ne phrotoxicity.

This study was considered Acceptable and meets the guidelines when use in conjunction with the “Final Report: 90 Day Oral Toxicity Study with “P4150" in Rats followed by a 4

- Week Recovery Period” (MRID 451519

- 01).

870.3250 90

- Day Dermal Toxic ity

– Rat

In a subchronic dermal toxicity/immunotoxicity study (MRID 45151902), 1,3

- PAD ( purity of 29.3% a.i.) was administered to Sprague Dawley (Crl:CD

 BR) rats (8/sex/group for Cohort I and 15/sex/group for Cohort II) dermally via a wrapping procedure a t dose levels at 0, 5 (1.5 mg a.i.), 10 (2.9 mg a.i.), and 15 (4.4 mg a.i.) mg/kg

- day (dose reduced from 20 [ 5.9 mg a.i. ] mg/kg/day during week 1) for a period of 28 days for animals in Cohort I, and 14 weeks for animals in Cohort II.

No treatment

- relate d effects were observed in clinical chemistry, ophthalmology or organ weights. No immunosuppression was seen.

Cohort I parameters consisted of observations, immunotoxicity, food consumption and body weights and gross and histopathology of animals dying in extremis only. Cohort II measured parameters consisted of the above and clinical chemistry, ophthalmology, organ weights, and gross and histopathology of 10 surviving animals in the high dose group and the control.

In Cohort I/II, severe dermal irritation was noted in high

- dose animals during the first week of dosing which resulted in a decrease of the high dose from 20 (5.9 mg a.i.) mg/kg

- day to 15 (4.4 mg a.i.) mg/kg

- day. Dermal irritation persisted after the reduction of the dosage level, and began
to a lso appear in the low

- and mid

- dose groups. Females showed greater dermal irritation than the males.

In Cohort II, decreases in mean body weight gain (not statistically significant) were noted in the mid (12%) and high

- dose (14%) males during the study. A dditionally, a significant increase inPage 31 of 50

food consumption was noted in mid

- and high

- dose females from week 6 ( except for week 10 ) through the end of the study.

In Cohort II, increases in absolute white blood cells, absolute neutrophils, and absolute and

re lative eosinophil counts, and a decrease in relative lymphocyte count were seen in high

- dose females and a significant increase in the relative eosinophil count were noted in mid

- dose female rats.

Treatment

- related microscopic lesions were observed at th e app lication site (skin. all doses)

, axillary lymph nodes, (mid and high dose) and sternal bone marrow (all doses, except low dose males).

1. 28 Day Dermal/Immunotoxicity :
The study was unacceptable as a 28 Day Dermal toxicity study and lacking hematology , clinical chemistry and gross and microscopic pathology but measuring body weight, food consumption and observations. This study was performed mainly to measure immunotoxicity study. Other than dermal irritation in point 3 below body weight was decreased by 14% in the high dose males. T his decrease was not statistically significant.

No immunosuppression was seen. NOAEL >15 (4.4 mg a.i.)/20 (5.9 mg a.i.) mg/kg/day (HDT). The LOAEL could not be calculated.

This study is classified as Acceptable and meets the guideline requirements of 870.7800 for a n i mmunotoxicity s tudy.

2. Subchronic 90 Day study

The LOAEL is 5 (1.5 mg a.i.) mg/kg/day ( lowest dose tested [ LDT ] ) was based on sternal bone marrow hyperplasia in the female. The NOAEL is <5 (1.5 mg a.i.) mg/kg/d ay.
This subchronic 90 Day study toxicity study is classified as Acceptable and meets the guideline requirements of 870.3250 for a 90 Day Dermal Toxicity Study

. Developmental Toxicity

Adequacy of Database for Prenatal Developmental Toxicity: The databas e for prenatal developmental toxicity is considered inadequate for the currently registered uses. D developmental toxicity assessment for 1,3

- PAD is based on a developmental study in the rat (MRID 45115322 ). A developmental toxicity study in non

- rodent spec ies is anticipated to be required, based on the adverse effects observed in the available data and the currently registered

uses

.
870.3700 Prenatal Developmental Toxicity (Gavage) Study

– Rat

(1) In a dose range finding developmental toxicity study (MRID 45115322), 1,3

- PAD ( purity of 30.2% a.i.) was administered daily to mated Sprague

- Dawley CD albino rats (8 females/group), via oral gavage at dose levels of 25 (7.5 mg a.i.), 50 (15.0 mg a.i.), 100 (30.2 mg a.i.) and 150Page 32 of 50

(45.3 mg a.i.) mg/kg / day for a peri od of 10 days, over gestational days 6

- 16. All animals were sacrificed at Day 20 of the gestation period. An additional 8 un

- mated female rats were similarly dosed with 200 (60.4 mg a.i.) mg/kg / day for 7 consecutive days, after completion of the screening study, with the purpose of verifying questionable toxicity findings. The oral route of test article administration was chosen as it is a possible route of exposure in humans.

Treatment

- related findings included clinical observations of post

- dosing salivat ion, with some brown staining, in most females of the two high

- dose groups . Salivation was also observed in most of the unmated females dosed at 200 (60.4 mg a.i.) mg/kg / day. Mean food consumption was marginally lower on the first day of dosing (Day 6 of gestation), compared to predose values. Mean food consumption was markedly decreased throughout dosing in females treated at 200 (60.4 mg a.i.) mg/kg / day, compared to predose values. Test substance, 1,3

- PAD

, had no effect on mean body weight or mean weight gain, pregnancy performance or fetal weight.

Based on these findings, the study authors determined that suitable dose levels for a teratogenicity study were 25 (7.5 mg a.i.), 75 (22.5 mg a.i.), and 200 (60.4 mg a.i.) mg/kg

- day.

The NOAEL for maternal t oxicity is 50 (15.1 mg a.i.) mg/kg/day and the LOAEL is 100 (30.2 mg a.i.) mg/kg/day based on decreased mean food consumption and salivation. The developmental NOAEL is 200 (60.4 mg a.i.) mg/kg/day and the developmental LOAEL is >200 (>60.4 mg a.i.) mg/kg/ day

. This study is Acceptable , but no guideline are available for this rangefinding study.

(2) In a developmental toxicity study (MRID 45151903), 1,3

- PAD ( purity of 30.2% a.i.) in distilled water was administered orally by gavage to mated female Sprague

- Da wley, Charles River CD (outbred albino) rats (25/dose) at dose levels (measured) of 0 (distilled water) , 25 (7.6 mg a.i.), 75 (22.7 mg a.i.), or 200 (60.4 mg a.i.) mg/kg/day from Days 6 through 16 of gestation. There was clear evidence of maternal effects in the high

- dose dams, including clinical signs of toxicity (dyspnea, piloerection, salivation associated with brown staining, and indications of reduced activity), premature sacrifice of 2 dams, reduced body weight during the dosing period, significantl y decreased body weight gain during the dosing period, significantly decreased mean food consumption during the dosing period, intestinal distension, increased incidence of early embryonic deaths, and increased number of total dead implants. Additionally, administration of mid

- dose result ed in a n i nsignificant reduction in mean body weight gain during the dosing period, a significant decrease in mean food consumption during the dosing period, and an increased incidence of dyspnea and salivation associated with brown staining.

No external, visceral or skeletal abnormalities/variations were observed in any of the treatment
groups.

The NOAEL for maternal toxicity is 25 ( 7.6 mg a.i. [LDT]) mg /kg/day, and the LOAEL for maternal toxicity is 75 ( 22.7 mg a.i. ) mg /kg/day , based on clinical signs of toxicity and decreased mean body weight gain and mean food consumption. The developmental NOAEL is 200 ( 60.4 mg a.i. ) mg/kg/day, and the developmental LOAEL could not be established

, based on no developmental toxicity wa s observed i n any of the treatment groups.Page 33 of 50

This study in the rat is classified as Acceptable and meets the g uideline requirement of OPPTS 870.3700 for a developmental study in rats

. Reproductive Toxicity

Adequacy of Database for Reproduction and Fertility Effects: The database for reproductive toxicity is considered to be adequate for the currently registered uses. Assessment of reproduction and fertility effects for 1,3

- PAD is based on a two

- generation reproduction study in
rats (MRID 451519 04) in the a g ency’s hazard database

. No additional data are anticipated to be required.

870.3800 Reproduction and Fertility Effects

– Rat

In a two

- generation reproduction study (MRID 451519 04), 1,3

- PAD ( purity of 30.2% a.i.) in distilled water was administered orally b y gavage to male and female Sprague

- Dawley Charles River CD (outbred albino) rats at dose levels of 0 (distilled water) , 10 (3.0 mg a.i.), 30 (9.1 mg a.i.), or 90.0 (27.2 mg a.i.) mg/kg/day. F 0 males and females (28 rats/sex/group) were dosed 10 weeks pri or to mating. Treatment continued until termination (after the weaning of F 1 litters) and included mating, gestation, and lactation periods. F 1 animals (24 rats/sex/group) were treated at 25 days of age until the animals were paired for mating (approxima tely 11 weeks after weaning). Dosing was then resumed until termination (after the weaning of F 2 litters), and included mating, gestation, and lactation periods.

Maternal effects in the high

- dose dams includ ed clinical signs of toxicity (principally dysp nea, piloerection and hunched posture, and post

- dosing salivation), death of 8 animals (2 F 0 males, 3 F 0 females, 1 F 1 male, and 2 F 1 females), significantly decreased body weights in F 0 and F 1 males, decreased body weight gain in F 0 and F 1 males, decrease d body weight gain in F 0 and F 1 females during pre

- mating and gestation periods, and decreased mean food consumption in F 0 and F 1 males and females.

The NOAEL for parental toxicity is 30 ( 9.1 mg a.i.) mg/kg/day, and the LOAEL for parental toxicity is 90 ( 27.2 mg a.i.) mg/kg/day , based on clinical signs of toxicity, mortality, decreased mean body weight, decreased mean body weight gain, and decreased mean food consumption.

Mating performance, fertility, duration of gestation, litter size and pup survi v al were not affected by the test substance.

The NOAEL for reproductive t oxicity NOAEL is equal to/greater than (≥) 90 (27.2 mg a.i.) mg/kg/day (HDT), and the LOAEL for r eproductive t oxicity is greater than (>) 90 (27.2 mg a.i.) (not established).

Two pups sho wed body tremors and s light decreases in F 2 litter and pup weights were observed
at the high

- dose level

. The offspring toxicity NOAEL is 30 (9.1 mg a.i.) mg/kg/day, and the offspring toxicity LOAEL is 90 (27.2 mg a.i.) mg/kg/day , based on decreased litter and pup weights.Page 34 of 50

This reproductive toxicity study in the rat is classified Acceptable and satisfies the g uideline requirement of OPPTS 870.3700 for a reproductive/fertility toxicity study in rats

. 

## Chronic Toxicity / Carcinogenicity

Adequacy of D atabase f

or Chronic Toxicity/Carcinogenicity : A combined chronic toxicity and carcinogenicity study in rats (MRID s 48658501/02 ) is available in the a gency’s hazard database . The adequacy of this study will be determ ined once the a gency’s comprehensive review is co mpleted. 

## Mutagenicity

Adequacy of D atabase for Mutagenicity : The database for mutagenicity is considered adequate for the currently registered uses based on the EPA's 1991 mutagenicity guidelines . Several mutagenicity studies have been submitted and revi ewed by the Office of Pesticide Programs (OPP) and found acceptable

, except for the in vitro mammalian cytogenetics assay (MRID 451153 23)

. 1,3

- PAD is found to be mutagenic in in vitro mammalian cytogenetics assay

. The summaries of these studies are provide d below.

Gene Mutation

(1) In a bacterial reve rse mutation assay (MRID 451153 24), five histidine

- dependent strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537, and TA1538) were tested for reverse mutations with concentrations of 1,3

- PAD ranging from 0.24

- 150 μg/plate

- S9 activation, and 0.96

- 600 μg/plate +S9 activation. S. typhimurium was cultured for 2 days with test chemicals and then the colonies were counted using an image analyzer. No P4150 treatment resulted in the
two

- fold (strains TA98 and TA100) or three

- fold (strains TA1535, TA1537, and TA1538) increase in mean revertant numbers that would indicate a positive response.

In this assay , 1,3

- PAD did not cause mutagenic activity

. This study is classified as Acceptable and satisfies the gui deline requirement of OPPTS 870.5100 for a bacterial reverse mutation assay in S. typhimurium

. (2) The test article, 1,3

- PAD (purity of 29.5% a.i

. ) , was evaluated in a mammalian forward mutation assay at six dose levels (0.05, 0.1, 0.5, 1.0, 2.5 and 5.0 μ g /mL) in Chinese hamster V79 cells (MRID 451153 25 ) . The test doses were based on cytotoxicity results from a preliminary
range

- finding experiment using doses ranging from 0.0016

- 5.0 mg/mL. In the main and confirmatory assays, mutagenicity was tested in the absence and presence of rat liver S9 fraction (±S9) . Two subsequent assays were conducted to assess mutagenicity and cytotoxicity. Relative and absolute cloning efficiencies were calculated at the conclusion of the selection period; was assessed using a 6

- thioguanine selection assay. Criteria for a valid assay were not provided. Minimal criteria for a positive response (statistical evaluation of all MF implementing a t

- test, p= 0.05) were listed in the study report. The sensitivity of the system to detect m utations was shown by the induction of high MF values by the positive controls,

- S9.

The test article did not induce a significant increase in mutation frequency (MF) at any dose or condition.Page 35 of 50

This study is classified as Acceptable and satisfies the guidel ine requirements of OPPTS 870.5300 for a n In Vitro Mammalian Cell Gene Mutation Test.

Cytogenetics

(1) In an in vitro mammalian cytogenetics assay (MRID 451153 23) with 1,3

- PAD ( purity of 29.5% a.i.), Chinese hamster V79 cells were tested at concentrations ranging from, 10.0 to 0.1 μg/ml, ±S9. Toxicity (based on decreases in the mitotic indices) was seen at doses of 10.0 and 5.0 μg/ml in the absence of S9 and at 10.0 μg/ml in the presence of S9. No increase in the percentage of cells with aberrations was o bserved for any test concentration at any harvest time, with or without S9 activation. How ever, a significant dose

- depende nt increase of polyploid cells was observed after both 17 as well as 24 hours + S9. This effect was reproduced in the second
test.

The test material was considered a mutagen , causing the production of polyploid cells after both 17 and 24 hours.

This study is classified as Unacceptable/upgradeable , and does not satisf y the guideline requirement [OPPTS 870.5375] for an in vitro mammalian cytogenetics study in mammalian cells. Reporting of the data is unclear with respect to the first test and second test and with regard to what is actually measured. Statistical methods were not used in the evaluation of the data and there are no recommende d guidelines as to what criteria are used for a positive study.

(2) In a mouse bone marrow micronucleus assay (MRID 463426 01), 3 Crl:CD

- 1® (ICR) BR mice/sex/dose were exposed once by intraperitoneal injection (i.p.) to 1,3

- PAD (purity of 90% a.i. ) dissolv ed in water at doses of 8, 16, 31.25, 62.5, 125, 250 or 500 mg/kg. Animals were observed for clinical toxicity signs after dosing of test article, 1

- hour following, and at least once a day for 48 hours after dosing. The maximum tolerated dose was estimated to be 8 mg/kg. No differences were observed between sexes and only males, therefore, were used in the main study.

In the main study, 1,3

- PAD (purity of 90% a.i. ) in deionized water was administered at 0 (control), 2, 4, and 8 mg/kg by i/p. to male Crl:C D

- 1® (ICR)BR mice. Bone marrow was harvested at 24 hours, from 6 animals/dose level. After 48 hours 6 animals from the vehicle control and 6 animals from the 8.0 mg/kg dose level were sacrificed and the bone marrow harvested. The positive control article, cyclophosphamide, dissolved in water, was administered once by oral gavage at 80 mg/kg, and the bone marrow harvested after 24 hours.

Animals dosed at 2 and 4 mg/kg bw and sacrificed after 24 hours, showed signs of hypertension of the back, hunched postur e, and squinted eyes, one hour post dosing. These clinical toxicity observations were not noticed one day after dosing. Animals dosed at 8 mg/kg bw and sacrificed after 24 hour and 48 hours showed signs of hyperextension of the back, hunched posture, squin ted eyes, irregular respiration, and slight hypoactivity one hour after dosing.

The positive and negative controls showed the appropriate response. 1,3

- PAD (purity of 90% a.i. ) was considered to be negative in the mouse bone marrow micronucleus assay und er the test conditions of the assay at both time periods.Page 36 of 50

This study is classified as Acceptable/Guideline and satisfies the guideline requirement of OPPTS 870.5395 for in vivo cytogenetic mutagenicity data, micronucleus test/mouse.

870.7800 Immunotoxici ty Study

Adequacy of Database for Immunotoxicity: A subchronic dermal toxicity/immunotoxicity study in rats (MRID 45151902) is available in the a gency’s hazard database . The a gency has reviewed the study and determined that the immunotoxicity portion of t he study was acceptable and met the guideline requirements for an immunotoxicity study. The study is summarized under the subchronic dermal study above. A summary of the immunotoxicity portion of the study (Cohort I) is provided below.

In a subchronic derm al toxicity/immunotoxicity study (MRID 45151902), 1,3

- PAD (purity of 29.3% a.i.) was administered to Sprague Dawley (Crl:CD

 BR) rats (8/sex/group for Cohort I and 15/sex/group for Cohort II) dermally via a wrapping procedure at dose levels of 0, 5 (1.5 mg a.i.), 10 (2.9 mg a.i.), and 20 (5.9 mg a.i.) mg/kg

- day (dose reduced to 15 [4.4 mg a.i.] mg/kg/day during week 1) for a period of 28 days for animals in Cohort I (28 Day Dermal/Immunotoxicity).

Cohort I parameters consisted of observations, immunotoxic ity, food consumption and body weights and gross and histopathology of animals dying in extremis only.

Severe dermal irritation was noted in high

- dose animals during the first week of dosing which resulted in a decrease of the high dose from 20 (5.9 mg a.i .) mg/kg

- day to 15 (4.4 mg a.i.) mg/kg

- day. Dermal irritation persisted after the reduction of the dosage level, and began to also appear in the low

- and mid

- dose groups. Females showed greater dermal irritation than the males.

Decreased body weight (14%; not statistically significant) were observed in the high dose males. No immunosuppression was observed.

The immunotoxicity NOAEL was determined to be >15 (4.4 mg a.i.)/20 (5.9 mg a.i.) mg/kg/day (highest dose tested [HDT]). The LOAEL could not be calculat ed.

This study is classified as Acceptable and meets the guideline requirements of 870.7800 for an Immunotoxicity Study.

Other Special Studies

There are one metabolism study (MRID 45115326) and one in vitro percutaneous absorption study (MRID 46309705) stu dies in the agency’s hazard database. The a gency has reviewed these studies and determined they are acceptable. Summaries are provided below.

870.7485 M etabolism and Pharmacokinetics

In a metabolism study (MRID 45115326), radioactive ( 14 C) 1,3

- PAD ( > 97% a .i. for radiolabeled, 99.8% a.i. for non

- radiolabeled) suspended in water, was administered orally to male and female Sprague Dawley CD ® rats at a dose of 3 or 30 mg/kg. The biokinetics,Page 37 of 50

metabolism, tissue distribution, and proportion of metabolites were i nvestigated over a 120

- hour duration. No animals were reported to exhibit any signs of toxicity. There were no dose

- or sex

related differences in 14 C

- labeled test substance excretion. Approximately 90%

- 97% of radioactive test substance was excreted in the feces of both sexes by the 120 th hour. Percent radioactivity recovered in the carcasses and gastrointestinal tracts of either treated sex ranged from 1.0%

- 3.0% and 0.4%

- 1.3%, respectively. Percent radioactivity excreted via urine (2%) and expired air (0.1 %

- 0.4%) were minimal regardless of dose or sex. Based upon excretion data, the oral administration of single doses of 3 and 30 mg/kg resulted in approximately 0.2% gastrointestinal absorption regardless of sex. Low 14 C

- labeled test substance plasma
concent rations support this conclusion. Detectable 14 C

- labeled test substance radioactivity in the plasma was generally below the limit of reliable measurement for both the 3 and 30 mg/kg doses. Peak concentrations (0.12 μg equiv./mL) were reported at 4 and 12 ho urs after low and high dose administration, respectively. The half

- life plasma concentrations after a 30 mg/kg dose were determined to be 28.5 and 46.3 hours for males and females, respectively. Concentration versus time curve (AUC t ) values were calculated at 4.6 μg equiv./mL hour for males and 5.1 μg equiv./mL hour for females. Five male rats were treated (3 mg/kg) and subjected to whole

- body autoradiography. The highest levels (qualitative data measured visually) of radioactivity were distributed througho ut the gastrointestinal tract and its contents. Low levels (qualitative data measured visually) of the test substance were present in other tissues, providing additional evidence for low oral absorption.

The parent structure was the major compound found i n the feces after low (11% females and 13% males) or high doses (7% females and 10% males). Six minor metabolites were detected in the feces after both doses, although all were minor and individually represented 1%

- 3% of the administered doses. One of thes e metabolites was identified as 1

- dodecylamine, the proposed biotransformation pathway. Other unidentified metabolites accounted for <3% of the total radioactivity administered. A considerable portion of the dose (66%

- 72%) remained unextracted after either of the doses. Further extraction released an additional 17%

- 20% (low

- dose) and 20%

- 25% (high

- dose); the analysis afterwards was unsuccessful.

In comparing this study to the guideline requirements for a toxicokinetic study (OPPTS 870.8500) in rats, the st udy would not satisfy the requirement that the highest dose did not produce any clinical indications of toxicity.

This short

- term toxicity study is classified as Acceptable and fulfills the guideline requirements of OPPTS 870.7485 for a Metabolism study.

8 70.7600 Dermal Penetration

In a non

- guideline in vitro percutaneous absorption study (MRID 46309705), 1,3

- PAD (97.1% a.i., Batch No. KV021704), and [ 14 C]

- 1,3

- PAD in the form of a hydrochloride salt (98.3% radiochemical purity, specific activity of 25.7 mC i/mmol, lot No. 3494

- 134), was applied to de r matomed human skin samples, in vitro, and adsorption was measured via a flow through diffusion cell system after 24 hours of exposure. The test article at 108.12 μg equiv/cm 2 in water (  1%) was administered to 1 1 donor skin samples (200

- 500 μm thick stratum corneum) from 6 female human donors to an area of 0.64 cm 2 at 10 μL/cm 2 . The skin samples were obtained from 4 breasts and 3 abdomens from routine plastic surgery patients between the ages 24 and 66 years.Page 38 of 50

T he 1% (w/v) [ 14 C]

- 1,3

- PAD / 1,3

- PAD solution was poorly absorbed with dermal absorption and dermal delivery being <0.01% and 0.92% of the applied dose, respectively. The system had acceptable recovery with a mean mass balance of 102.14% of the applied dose.

This study in human skin is classified as Acceptable/Non

- guideline . The a gency does not have a guideline for such a study. In vitro testing does not account for the influence of systemic distribution and excretion kinetics upon dermal absorption of the ch emical of concern; therefore, in vitro studies alone do not satisfy the guideline requirements of OPPTS 870.7600 for a Dermal Penetration study.

The toxicology profile for 1,3

- PAD is summarized in Table 12 below

.

Table 12

– Toxicology Profile for 1,3

- PAD

Guideline No./Study Type/ Substance Purity MRID No. (year) Results

Subchronic Toxicity

Non

- guideline 90

- Day oral toxicity (range

- finding) rodents

- Rat purity unknown 45115319 (1992) NOAEL = 10 mg/kg/day

LOAEL = 60 mg/kg/day, based on microscopic evidence of submucosal and mucosa gastritis and glandular epithelial degeneration.

870.3100 90

- Day oral toxicity rodents

- Rat purity 29.8% 45151901 (1992) NOAEL = 5 (1.5 mg a.i.) mg/kg/day

LOAEL = 10 (3.0 mg a.i .) mg/kg/day, based on based on the clinical finding of a reduced righting reflex

.

Non

- guideline A histopath review of MRID 45151901 45115320 (1999) NOAEL = 30 (8.9 mg a.i.) mg/kg/day

LOAEL = 90 (26.8 mg a.i.) mg/kg/day, based on nephrotoxicity
870.325 0 90

- Day dermal toxicity

– Rat purity 29.3% 45151902 (2000) NOAEL < 5 (1.5 mg a.i.) mg/kg/day (LDT)

LOAEL = 5 (1.5 mg a.i.) mg/kg/day, based on sternal bone marrow hyperplasia in the female

870.3465 90

- Day inhalation toxicity No studies available.

Dev elopmental/Reproductive Toxicity
870.3700 Prenatal developmental (range

- finding) rodents

– Rat purity 30.2% 45115322 (1993) Maternal Toxicity NOAEL = 50 (15.1 mg a.i.)

mg/kg/day Maternal Toxicity LOAEL = 100 (30.2 mg a.i.) mg/kg/day, based on ↓ mean food consumption and salivation.

Developmental Toxicity NOAEL = 200 (60.4 mg a.i.) mg/kg/day (HDT) Developmental Toxicity LOAEL > 200 (60.4 mg a.i.) mg/kg/day (not established)Page 39 of 50

Guideline No./Study Type/ Substance Purity MRID No. (year) Results

870.3700 Prenatal developmental in rodents

– Rat purity 30.2% 4515 1903 (1994) Maternal Toxicity NOAEL = 25 (7.6 mg a.i.) mg/kg/day

(LDT) Maternal Toxicity LOAEL = 75 (22.7 mg a.i.) mg/kg/day, based on clinical signs of toxicity and ↓ mean body weight gain and mean food consumption

. Developmental Toxicity NOAEL = 200 (60 .4 mg a.i.) mg/kg/day (HDT) Developmental Toxicity LOAEL > 200 (60.4 mg a.i.) mg/kg/day (not established)

870.3800 Reproduction and fertility effects

– Rat purity 30.2% 45151904 (1995) Parental/Systemic Toxicity NOAEL = 30 ( 9.1 mg a.i.)

mg/kg/day Parental /Systemic Toxicity LOAEL = 90 (27.2 mg a.i.) mg/kg/day, based on clinical signs of toxicity, mortality, ↓ mean body weight/body weight gain, and ↓ mean food consumption.

Reproductive Toxicity NOAEL ≥ 90 (27.2 mg a.i.) mg/kg/day (HDT) Reproductive Toxicity LOAEL > 90 (27.2 mg a.i.) mg/kg/day (not established)

Offspring Toxicity NOAEL = 30 ( 9.1 mg a.i.) mg/k g/day Offspring Toxicity LOAEL = 90 (27.2 mg a.i.) mg/kg/day, based on ↓ litter and pup weights.

Chronic Toxicity/Carcinogenicity

870.4300 Comb. Chronic Toxicity/Carcinogenicity

– Rats purity 89.4% 48658501/02 (2011) Under the a gency’s review.

Mutage nicity

870.5100 Ames Assay purity 30% 451153 24 (1988) Negative

870.5300 In vitro Mammalian Cell Gene Mutation Test purity 29.5% 451153 25 (1991) Negative

870.5375 In vitro Mammalian Chromosomal Aberration Assay (CHO) purity 29.5% 451153 23 (1991) Posit ive

870.5385 In vivo Mammalian Bone Marrow Micronucleus Assay

- Mouse purity 90% 46342601 (2004) NegativePage 40 of 50

Guideline No./Study Type/ Substance Purity MRID No. (year) Results

Immunotoxicity

870.7800 Immunotoxicity purity 29.3% 45151902 (2000) NOAEL ≥ 15 (4.4 mg a.i.)/20 (5.9 mg a.i.) mg/kg/day

(HDT) LOAEL > 15 (4.4 mg a.i.)/20 (5.9 mg a.i.) mg/kg/day (not established) Special Studies
870.7485 Metabolism and Pharmacokinetics purity > 97% for radiolabeled and 99.8% for non

- radiolabeled 45115326 (19 96) Approximately 0.2% GI absorption rate was estimated

after a single oral dose of 3 and 30 mg/kg of 1,3

- PAD

. 1,3

- PAD was excreted primarily in the feces (90

- 97% vs 2% in urines) of both sexes by the 120 th hour. Detectable 14 C

labeled 1,3

- PAD radioactivit y in the plasma was generally below the limit of reliable measurement for both the 3 and 30 mg/kg doses. Peak concentrations (0.12 μg equiv./mL) were reported at 4 and 12 hours for low and high dose administration, respectively. The half

- life plasma

concen trations after a 30 mg/kg dose were determined to be 28.5 and 46.3 hours for males and females, respectively. No differences were observed in the absorption, distribution, or excretion patterns in male and female rats in any of the dose groups.

The parent structure was the major compound found in the feces after low (11% females and 13% males) or high doses (7% females and 10% males). One of these metabolites was identified as 1

- dodecylamine, the proposed biotransformation pathway. A considerable portion o f the dose (66%

- 72%) remained unextracted after either of the doses. Further extraction released an additional 17%

- 20% (low

- dose) and 20%

- 25% (high

dose); the analysis afterwards was unsuccessful.
Non

- Guideline In Vitro Percutaneous Absorption purity 98.3 % for radiolabeled and 97.1% for non

- radiolabeled 46309705 (2003) The 1% (w/v) [ 14 C]

- 1,3

- PAD / 1,3

- PAD solution was poorly

absorbed with dermal absorption and dermal delivery being <0.01% and 0.92% of the applied dose, respectively. The system had acceptable recovery with a mean mass balance of 102.14% of the applied dose.Page 41 of 50 

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of 1,3

- PAD

1,3

- PAD is a propane diamine compound that is miscible in water and is unlikely to move from soil or water i nto air based on the vapor pressure of 3.3 x 10

- 6 mm Hg and the Henry’s Law constant of 1.3 x 10

- 10 atm m 3 mol

- 1 (Table 4). While it was not included in the ATMD RED for alkyl trimethylene diamines, 8

, 9 it is a diamine compound with similar structural, chem ical and physical characteristics to those in the RED. Other than hydrolysis, no additional environmental fate data have been submitted for 1,3

- PAD

.

Water and Sediment

Hydrolysis

1,3

- PAD was stable to hydrolysis at pH 5,7

, and 9 (MRID 45115327).

Aqu eous and Soil Photoly s is

1,3

- PAD is not susceptible to photodegradation based on its lack of sorption of UV light between 290 and 800 nm in wavelength ( Table 4 ).

Octanol

- Water Partition Coefficient

1,3

- PAD is a polar, m iscible substance and data on octanol and water partitioning are not required ( Table 4 ).

Aerobic Aquatic Metabolism

Data on aerobic aquatic metabolism are anticipated to be required based on the registered uses that have the pot ential to create environmental exposure. The metalworking fluid use can create down

- the

- drain exposure from release of used metalworking fluids to WWTPs and the oilfield uses can create environmental exposure through runoff or leaching from water holding p onds or through effluent water from WWTPs.

A n a erobic Aquatic Metabolism

Data on aerobic aquatic metabolism are anticipated to be required based on the registered uses that have the potential to create environmental exposure. The metalworking fluid use ca n create down

- the

- drain exposure from release of used metalworking fluids to WWTPs and the oilfield uses can create environmental exposure through runoff or leaching from water holding ponds or through effluent water from WWTPs.

8 http://www.epa.gov/oppsrrd1/REDs/atmd

- red.pdf

9 The ATMD RED included PC codes (067301, 067302, 067309, 067310, and 067313.Page 42 of 50

Soil

Soil Leaching/Adsorp tion/Desorption Batch Equilibrium

Data on sorption to soil and sediment are anticipated to be required based on the registered uses that have the potential to create environmental exposure. The metalworking fluid use can create down

- the

- drain exposure from release of used metalworking fluids to WWTPs and the oilfield uses can create environmental exposure through runoff or leaching from water holding ponds or through sludge from WWTPs.

Aerobic Soil Metabolism

Data on aerobic soil metabolism are anticipated to be required based on the registered uses that have the potential to reach soil from sorption to sludge in wastewater treatment plants (WWTPs).

A n a erobic Soil Metabolism

Data on anaerobic soil metabolism are not anticipated to be required because usab le data on anaerobic aquatic metabolism may be used as a surrogate.

Fate and Transport in WWTP

Activated Sludge Sorption Isotherm

Data on sorption to activated sludge are anticipated to be required because the registered uses have the potential to reach WW TPs where they can sorb to sludge.
Biodegrada tion in WWTP

Data on ready biodegradability or one of three biodegradation in activated sludge simulation
tests are anticipated to be required because the registered uses have the potential to reach WWTPs where the extent of biodegradation during wastewater treatment is unknown

. Activated Sludge Respiration Inhibition

Data on activated sludge respiration inhibition (ASRI) are anticipated to be required because the registered uses have the potential to reach WW TPs where they could adversely affect microorganisms.

Table 13

– Summary of Chemical, Physical, and Environmental Fate Properties

Table 2. Physical, Chemical, and Environmental Fate Properties for 1,3

- PAD

Property OCSPP Guideline No. (unless stated) Value Citation

CAS No. None 2372

- 82

- 9 NonePage 43 of 50

Chemical and Physical Properties
Molecular weight (grams/mol) None 299.54 None

Water solubility (mg/L) 830.7840 Miscible 10 Table 4

Vapor Pressure (mm Hg) 830.7950 3.3 x 10

- 6 Table 4

Henry ’s Law (atm m 3 mol

- 1 ) 11 None (calculated) 1.3 x 10

- 10 None

Log P (unitless) 830.7550 Not required 12 Table 4

UV Visible absorption (nm) 830.7050 Sorption at 203

- 218 nm Table 4

Environmental Fate Properties

— Chemical Degradation (half

- lives in days unless s tated) Hydrolysis 835.2120 Stable at pH 5, 7, and 9 46309708

Photodegradation in water 835.2240 Not required 13 None

Photodegradation on soil 835.2410 Not required 14 None

Environmental Fate Properties

— Laboratory Metabolism (half

- lives in days unless sta ted)
Aerobic soil metabolism 835.4100 No data None

Anaerobic soil metabolism 835.4200 No data None

Aerobic aquatic metabolism 835.4300 No data None

Anaerobic aquatic metabolism 835.4400 No data None

Environmental Fate Properties

— Sorption to soil ( L/k g for Kd and Koc values ) Leaching

- adsorption

- desorption 835.1230 No data None

Wastewater Treatment Plant Properties

— Sorption and Degradation Activated sludge sorption isotherm (L/kg) 835.1110 No data None

Ready biodegradability or one of three biodegra dation in activated sludge simulation tests (%) 835.3110 or one of: 835.3220 835.3240 835.3280 No data None

Activated sludge respiration inhibition (mg/L). 850.3300 No data None

10 10,000 mg/l used in calculations

11 [VP (m m Hg) * molecular weight (grams/mol)]/[760 * water solubility (mg/l)]

12 1,3

- PAD is a polar compound and log P data are not required and not applicable

13 Not required based on l ack of UV sorption from 290

- 800 nm
14 Not required based on l ack of UV sorption f rom 290

- 800 nmPage 44 of 50

Environmental Fate and Transport References :

45115304 Sloan, R. (1999) Lonz abac 12

- Physical and Chemical Properties: Lab Project

Number: SP

- 99043

- A. Unpublished study prepared by Lonza, Inc. 30 p. {OPPTS 830.6315, 830.7000, 830.7050, 830.7100, 830.7300}
45115305 Sarff, P.; Edgar, L. (1999) Boiling Point Determination of Lonzaba c 12: Lab

Project Number: SP

- 99005

- A: 45066. Unpublished study prepared by ABC Laboratories, Inc. 14 p. {OPPTS 830.7220}

45115307 Sloan, R. (1999) Lonzabac 12

- Stability to Normal and Elevated Temperatures,

Metals and Metal Ions: Lab Project Number: SP

- 990 10

- A. Unpublished study prepared by Lonza Inc. 24 p. {OPPTS 830.6313}

45115308 Lonza, Inc.; Lewis and Harrison, LLC. (2000) Product Chemistry: Discussion of

Physical and Chemical Properties: Lonzabac 12. Unpublished study. 7 p. {OPPTS 830.6304, 830.6317, 830.6320}

45115309 Lonza, Inc.; Lewis and Harrison, LLC. (2000) Product Chemistry: Vapor Pressure

for Lonzabac 12. Unpublished study. 8 p. {OPPTS 830.7950}

46309706 Sarff, P. (1999) Corrosion Characteristics of Lonzabac 12. Project Number: 45065,

SP/990 04/A. Unpublished study prepared by ABC Laboratories, Inc. 15 p.

46309708 Spare, W. (2004) Aqueous Hydrolysis of (Carbon

- 14)

- Lonzabac 12 Under

Laboratory Conditions. Project Number: 065/002, EXP/065/002. Unpublished study prepared by Exygen Research. 106 p.
46332202 Sloan, R. (2000) Procedure for Determining Dodecylamine Content in Lonzaback

12. Unpublished study prepared by Lonza, Inc. 5 p. U.S. EPA. September, 2007. Reregistration Eligibility Decision (RED) for

Alkyltrimethylenediamines (Case 3014)

. EPA 739

- R

- 07

- 004

. http://www.epa.gov/oppsrrd1/REDs/atmd

- red.pdfPage 45 of 50 

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Organisms

Birds, acute oral

One available acute

- oral (LD50) study categorizes PAD as being highly toxic to birds. The guideline (850.2100) is satisfied. No additional data are anticipated to be required.

Avian Acute

- oral Toxicity

Test Species Test Material ( % ai) Toxicity Toxicity Category EPA Study ID

Northern bobwhite ( Colinus v irginianus ) Lonzabac 12 (24.3%) LD 50 = 25 mg ai/kg bw Highly toxic 451153

- 10 Supplemental 1

1 test material was not the TGAI


### Toxicity to Aquatic Organisms

Freshwater Fish, acute and chronic

The available acute toxicity studies categorize PAD as being hi ghly toxic to freshwater fish. The guideline (850.1075) for acute toxicity testing is satisfied. No chronic data are available. Because there may be continuous or repeated down

- the

- drain exposure s , chronic data are anticipated as being needed (fish early

- life stage, 850.1400). However, the anticipated t esting would be conducted with the most sensitive fish, either freshwater or estuarine/marine fish. The need for a freshwater early life

- stage toxicity test (850.1400) cannot be determined until estuarine/ma rine fish toxicity data are available.

Acute Toxicity of Iodine to Freshwater Fish

Test Species Test Material (% ai) Toxicity Endpoint (mg ai/L) Toxicity Category EPA Study

ID

Rainbow Trout ( Oncorhynchus mykiss) Lonzabac 12 ( 30.0% aqueous solution ) 96

- hr LC50 = 0.68 1 (2.26 mg/L nominal) High ly toxic 451153

- 11 Supplemental 2 Bluegill ( Lepomis macrochirus ) 95.2 (radio

- labeled) 96

- hr LC50 = 0.45 Highly toxic 451153

- 12 Acceptable

1 adjusted for the purity of the test material

2 numerous guideline deficienc ies, including test material was not the TGAI, concentrations were not measured for all nominal concentrations, and high variab ility in percent recovery (62.4

- 127.6 %)Page 46 of 50

Freshwater Invertebrates, acute and chronic

The acute toxicity studies for the waterfle a categorize s PAD as being very highly toxic to freshwater invertebrates. The guideline (850.1010) for acute toxicity testing is satisfied. Because there may be continuous or repeated down

- the

- drain exposure s , chronic data are anticipated as being needed ( life

- cycle, 850.1300). However, the anticipated testing would be conduc ted with the most sensitive invertebrate , either freshwater or estuarine/marine. A freshwater life

- cycle toxicity test (850.13 00) would be needed only if the acute tests indicate that t he freshwater species is more sensitive than the estuarine/marine species for which data are not currently available.

Freshwater Invertebrates

Test Species Test Material

(% ai) Toxicity Endpoint

(mg ai/L ) Toxicity

Category EPA Study ID

Waterflea ( Daphni a magna ) 29.3 48

- hr EC50 = 0.073 Very highly toxic 451153

- 13 Acceptable

Estuarine/Marine Fish and Invertebrates

No acute or chronic data are available . Acute toxicity studies needed for the TGAI include tests for a fish sp. (850.1075), a bivalve sp. (85 0.1025 or 850.1055), and one additional invertebrate sp. (850.1035). C hronic toxicity testing with estuarine/marine organisms (850.1400, 850.1350) would be needed only if the acute tests indicate that the estuarine/marine species are more sensitive than fr eshwater species.

Aquatic Plants

No toxicity data are available. To support the TGAI, two studies are anticipated as needed : a Tier II test with a vascular species (850.4400) and an algal toxicity Tier II test for green algae (850.4500). If the green a lgae EC50 is <1 mg ai/L (ppm), then additional testing would be needed for freshwater and marine diatoms (850.4500) and cyanobacteria (850.4550).Page 47 of 50

Ecotoxicity References:

45115310 Gallagher, S.; Grimes, J.; Beavers, J. (2000) Lonzabac 12: An Acute Or al Toxicity

Study with the Northern Bobwhite: Final Report: Lab Project Number: 289

- 114. Unpublished study prepared by Wildlife International, Ltd. 54 p. {OPPTS 850.2100}

5115311 Ritter, A. (1989) P4150: 96

- Hour Acute Toxicity Study (LC50) in the Rainbow

Trout: Lab Project Number: 232604: 0767. Unpublished study prepared by RCC Umweltchemie AG. 42 p. {OPPTS 850.1075}

45115312 Drottar, K.; Kendall, T.; Kruegar, H. (2000) Lonzabac 12: 96

- Hour Flow

- Through

Acute Toxicity Test with the Bluegill (Lepomis mac hrochirus): Lab Project Number: 289A

- 151A. Unpublished study prepared by Wildlife International, Ltd. 57 p. {OPPTS 850.1075}

45115313 Drottar, K.; Kendall, T.; Kruegar, H. (2000) Lonzabac 12: A 48

- Hour Flow

Through Acute Toxicity Test with the Cladoceran (Daphnia magna): Lab Project Number: 289A

- 150. Unpublished study prepared by Wildlife International, Ltd. 59 p. {OPPTS 850.1010}Page 48 of 50 

# Appendix D Screening Level Down

- the

Drain Analysis

No Down

- the

- Drain analysis was performed for 1,3

- PAD for this Preliminary Work P lan (see section 4.3.2)

.Page 49 of 50 

# Appendix E Product Chemistry

1,3

- Propanediamine,N1

- (3

- aminopropyl)

- N1

- dodecyl

- product chemistry information is summarized in Table E1 (Source: MRID Nos. 46332202, 45115304, 45115305, 46309706, 45115307, 45115308, 45115309 and Lonza MSDS).

Table 14

– Product Chemistry of 1,3

- Propanediamine,N1

- (3

- aminopropyl)

- N1

- dodecyl

Guideline Numbers Physical and Chemical Properties 1,3

- Propanediamine,N1

- (3

- aminopropyl)

- N1

- dodecyl

830.1550 Product identity and composition Refer to Table 6

830.1600 Description of materials used to

produce the product Confidential Business Information (CBI)

830.1620 Description of production process CBI 830.1650 Description of Formulation Process CBI

830.1670 Description of Formulation

Impurit ies CBI

830.1700 Preliminary analysis CBI 830.1750 Certified limits CBI 830.1800 Enforcement analytical method GC 830.1900 Submittal of samples CBI 830.6302 Color Clear liquid

830.6303 Physical State Liquid Viscous oily liquid 830.6304 Odor Mild ami ne

- like

830.6313 Stability Stable Materials to avoid: Acids 830.6314 Oxidation/Reduction Not reported 830.6315 Flammability Flash point over 149 oF 830.6316 Explodability Not explodable 830.6320 Corrosion Characteristic Not corrosive to packaging 830 .7000 pH at 25 °C 10.6 (1% aqueous solution)

830.7050 UV/Visible Absorption 203.6 nm; 201.6 nm; 218.4 nm; in methanol, acidic methanol and alkaline methanol solutions

830.7100 Viscosity 24.08 cSt at 20oC 10.93 cSt at 40oC

830.7200 Melting point (°C) Set ting point ≥10oC

830.7220 Boiling point (°C) The boiling point could not be determined due to decomposition of the test substance at approx

. 280oC 830.7300 Density (g/cm 3 ) 0.87 g/ml at 20oC 830.7370 Dissociation Constant pKa(s) pKa values: 9.3 ± 0.104 a nd 7.15 ±0.054 at 20oC 830.7520 Particle size, fiber length, & diameter Not required

830.7550 Log Kow PAD is a polar chemical substance and therefore log Kow is not required. 830.7840 Solubility in water (mg/L) at 25 o C Completely and infinitely solub le in water

830.7860 Solubility in organic solvents Soluble in organic solvents. Completely miscible at 20oC in Acetone, Ethyl acetate, and Methanol. 830.7950 Vapor pressure (mm Hg) 3.3 x 10

- 6 at 25oCPage 50 of 50

Product Chemistry R eferences :

Lonza. Lonzabac 12 M SDS.

http://bio.lonza.com/uploads/tx_mwaxmarketingmaterial/Lonza_ProductDataSheets_ Lonzabac_12_PDS.pdf

MRID 45115304. Sloan, R. (1999) Lonz abac 12

- Physical and Chemical Properties: Lab Project

Number: SP

- 99043

- A. Unpublished study prepared by Lonza, Inc. 30 p. {OPPTS 830.6315, 830.7000, 830.7050, 830.7100, 830.7300}

MRID 45115305. Sarff, P.; Edgar, L. (1999) Boiling Point Determination of Lo nzabac 12: Lab

Project Number: SP

- 99005

- A: 45066. Unpublished study prepared by ABC Laboratories, Inc. 14 p. {OPPTS 830.7220}

MRID 45115307. Sloan, R. (1999) Lonzabac 12

- Stability to Normal and Elevated

Temperatures, Metals and Metal Ions: Lab Project Num ber: SP

- 99010

- A. Unpublished study prepared by Lonza Inc. 24 p. {OPPTS 830.6313}

MRID 45115308. Lonza, Inc.; Lewis and Harrison, LLC. (2000) Product Chemistry: Discussion

of Physical and Chemical Properties: Lonzabac 12. Unpublished study. 7 p. {OPPTS 830 .6304, 830.6317, 830.6320}

MRID 45115309. Lonza, Inc.; Lewis and Harrison, LLC. (2000) Product Chemistry: Vapor

Pressure for Lonzabac 12. Unpublished study. 8 p. {OPPTS 830.7950}

MRID 46309706. Sarff, P. (1999) Corrosion Characteristics of Lonzabac 12. P roject Number:

45065, SP/99004/A. Unpublished study prepared by ABC Laboratories, Inc. 15 p.

MRID 46332202. Sloan, R. (2000) Procedure for Determining Dodecylamine Content in

Lonzaback 12. Unpublished study prepared by Lonza, Inc. 5 p.