Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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 Gowda

Risk Management Tina Pham Rose Kyprianou Emilia Oiguenblik Velma Noble

Office of General Counsel Philip Ross

Page 2 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov TERMS, ABBREVIATIONS AND SYMBOLS

A.I. or a.i. active ingredient ASRI a ctivated sludge r espiration i nhibition atm

- m 3 /mole a tmospheric pressure

- cubic meter per mole °C d egrees Celsius CAS Chemical Abstracts Service CFR Code of Federal Regulations CHO Chinese h amster o vary DCI data call

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

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

- observed

- adverse

- e ffect

- l evel Log K ow l ogarithm of the octanol

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

nm n anometers NOAEC no

- observed

- adverse

- effect

- c oncentration NOAEL n o

- o bserved

- a dverse

- e ffect

- l evel OCSPP Office of Chemical Safety and Pollution Prevention OECD Organization for Economic Co

- operation and Development OPP Office of Pesticide Programs ORE occupational and residential exposure PAD p opulation a djusted d ose PC Code Pesticide Chemical Code
Page 3 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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

- 10 logarithm of the acid dissociation constant of a solution ppm p arts p er m illion PWP Preliminary Work Plan RED Rere gistration Eligibility Decision 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 WWTP w astewater treatment plant 1,3

- PAD 1,3

- propanediamine, N

- (3

- aminopropyl)

- N

- dodecyl

Page 4 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov



### Table of Contents
1 Introduction

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

................................ ................................ ................. 7 1.2 Updates to the Workplan

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

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

................................ ................................ ............ 9 1.5 Use/Usage Description

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

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

................................ ................................ .................. 11 1.5.3 Usage Information

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

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

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

................................ ................................ ................................ ......................... 12 1.7.1 Human He alth

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

................................ ................................ ................................ ............... 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

................................ ................................ ............. 16 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 Pathways

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

................................ ................................ ............... 19 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

- Drain Analysis

................................ ............................ 20 4.4 Effects Analysis Plan

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

................................ ................................ . 21 6 Optional Label Changes

................................ ................................ ................................ ........ 2 2 7 Next Steps

................................ ................................ ................................ ............................. 22 8 References

................................ ................................ ................................ ............................. 23

Appendix A T oxicology Profile

................................ ................................ ............................... 25 Appendix B Environmental Fate

................................ ................................ ............................. 44
Page 5 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Appendix C Ecotoxicology Profile

................................ ................................ .......................... 48 Appendix D Screening Level Down

- the

- Drain Analysis

................................ ........................ 51 Appendix E Product Chemistry

................................ ................................ ............................... 52

List of Tables Table 1

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

- PAD

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

– Anticipated Registration Review Schedule

................................ ................................ .... 9 Table 3

– Chemical Identification of 1,3

- Propanediamine,N

- (3

- aminopropyl)

- N

- dodecyl

- ........ 10 Table 4

– Physical

- Chemical and Environmental Fate Properties for 1,3

- Propanediamine, N

- (3

- aminopropyl)

- N

- dodecyl

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

– Summary of 1,3

- PAD Registered Uses

................................ ................................ ........ 11 Table 6

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

- PAD

.................... 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

................................ ... 17 Table 10

– Ecological Effects Endpoints

................................ ................................ ...................... 20

Page 6 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov


## 1 Introduction

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

- Propanediamine, N

- (3

- aminopro pyl)

- N

- dodecyl

- , herein referred to as 1,3

- PAD

. T he FWP document 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 revie w 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

. 

## 1.1 Statutory and Regulatory Authority The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United States generally must be registered by th e USEPA based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided at http://www2.epa.gov/pesticide

- reevaluation

.
The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standa rd for registration. The regulations governing registration review begin at 40 CF R 155.40. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for eac h case. The docket is the Agency ’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registration review decision.



## 1.2 Updates to the Workplan Since the publication of the Preliminary W ork P lan ( PWP ) , the Agency has made the following updates:

• Updated Section 1.3, Case Overview.

Page 7 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

• Updated Table 1 and Section s 1.5.1, 1.6, 3.2, and 3.4 based on label changes submitted since the publication of the PWP, specifying non

- food use onl y. D ietary (food) and T olerance R eview assessments are no longer anticipated for registration review.

• Updated the timeline in Table 2, Anticipated Registration Review Schedule.

• Revised Table 6, Studies Anticipated as Needed for the Registration Review of 1,3

- PAD to include guideline 835.1110 . This data gap was identified in Appendix B of the PWP but not captured in Table 6

.
• Updated Section 6, Optional Label Changes.

• Deleted the “Guidance for Commenters” section.

• Updated S ection 7, Next Steps.

• Updated Appendix A, including the A gency’s final review of chronic toxicity and carcinogenicity and Toxicology References.
No public comments were received on the initial docket and no modifications were made to the anticipated data needs or registration review schedule of the 1,3

- PAD PWP. This document makes final the work plan for the 1,3

- PAD registration review process.



## 1.3 Case Overview

The PWP for 1,3

- PAD was published on September 24, 2014
, and the 60

- day comment period ended on November 24, 2014. No public comments were received concerning the PWP. 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 summarize the issues relevant to this registration review case and the anticipated registration review schedule

.
Table 1

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

- PAD

Risk Assessment Assessment Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed (See Table 6 for detail s)

Dietary (food) No (See Section 3.2) N/A None None
Dietary (drinking water) Yes 1 N/A New None 1

Occupational Handler Yes 11/7/2007 New 90

- Day Inhalation Toxicity Prenatal Developmental Toxicity Dermal Indoor Exposure Inhalation Indoor Exposure Product Use Occupational Post

Application No (See Section 3.3.2) N/A None None

Residential Handler No (See Section 3.3.3) N/A None None

Page 8 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Risk Assessment Assessment Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed (See Table 6 for detail s)

Residential Post Application

- Incidental Oral and Dermal Yes 8/3/2005 Updated Prenatal Developmental Toxicity Indoor Residue Product Use Description of Human Activity
Residential Post Application

- Inhalation No (See Section 3.3.4) N/A None None
Aggregate Yes N/A New None 1

Cumulative No (See Section 3.4.2) N/A None None

Tolerance Review No N/A None None

Ecological Yes N/A New Down

- the

- Drain Ecotoxicology Environmental F ate (See Table 6)

1 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
Anticipated 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 2014

- 11

- 24 Phase 2: Case Development Issue Final Work Plan 2015

- 03 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

- 10 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 necessary ( e.g ., need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case).


## 1.4 Chemical Identification and Properties

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

- Propanediamine,N

- (3

- aminopropyl)

- N

- dodecyl

- (PC Code 067300)

.

Page 9 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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, 45115307, 45115308, 45115309
, 46309706, and Lonza MSDS) are discussed in Appendix E

.
Table 4

– Physical

- Chemical and Environmental 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

Page 10 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov



## 1.5 Use/Usage Description
1.5.1 Registrations
There are four registered 1,3

- PAD products . Since the publication of the PWP, a voluntary cancellation request has been submitted for one product (EPA Reg. No 6836

- 284)

. A ll remaining products are currently registered for non

- food uses . There are no inert uses and no pending registrations. 

### 1.5.2 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 by 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 Dairy Farm Premises Poultry Premises Animal Housing Facilities Mop 3.6 ppm Foaming Generator 3.2 ppm Mechanical Sprayer 3.6 ppm Commercial, Industrial, Institutional, Premises and Equipment

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

Beverage and Food Processing Plants Mop 3.6 ppm Foaming Generator 3.2 ppm Mechanical Sprayer 3.6 ppm
Residential and Public 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 Mechanical Sprayer 3.6 ppm Medical/Dental/Veterinary Premises and Equipment

Pet Shops Mop 3.6 ppm Foaming Generator 3.2 ppm
Page 11 of 5 3Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Use Application Method Application Rate Mechanical Sprayer 3.6 ppm
Preservatives Metalworking Fluids (Enclosed) Metering Pump 2500 ppm Oil Field Flood Water Systems Metering Pump 20 ppm



### 1.5.3 Usage Information

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

- PAD.



## 1.6 Regulatory Histor y
A Reregistration Eligibility Decision (RED) was not completed for 1,3

- PAD because it was registered after November 1, 1984. In 2015, labels were amended t o specify that products must only be used i n non

- food

- use areas.


### 1.6.1 Tolerance Information
For the active in gredient 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) Section 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.

The Agency does not anticipate reviewing the potential need for tolerances/exemptions during the registration review process for the currently registered non

- food uses

. 

## 1.7 Incidents
1.7.1 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

. 

### 1.7.2 Eco logical
There 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.

Page 12 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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 Exposure Scenario

835.1110 Activated sludge sorption isotherm (ASSI) TGAI 12 Environmental exposure All Ecological and drinking water exposure
835.1230 Leaching

- adsorption

- desorption TGAI 12 Environmental exposure All Ecological and drinking water exposure 835.3110 835.3220 835.3240 835.3280 Ready biodegradability or one of three biodegradation in activated sludge simulation tests 1,2 TGAI 12 Environmental exposure All Ecological and drinking water exposure

835.4100 Aerobic soil metabolism TGAI 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 All Ecological and drinking water exposure 850.1025

or 850.1055 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

850.1075 Estuarine/marine fish, acute toxicity TGAI 12

- 18 Saltwater fish All Down

- the

- drain

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

- the

- drain

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

- the

- drain
850.3300 or OECD 209 Activated sludge respiration inhibition (ASRI) 2 TGAI 12 Toxicity to WWTP organisms All Ecological and drinking water exposure
850. 4400 Aquatic plant toxicity, Lemna sp. 3 TGAI 12 Aquatic organisms All Down

- the

- drain

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 Cyanobacteria 3 Tier II TGAI 12 Aquatic plants All Down

- the

- drain

Page 13 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

GLN Study Name Test Substance Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data

Requirement Applicable Exposure Scenario

870.3465 90

- Day Inhalation Toxicity TGAI 12 Occupational handlers Hard surface disinfectant and sanitizer Mopping ; sprayer; foaming

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; foaming

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 Residential 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 Ingestion 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 biodegradation stud ies will be based on results of an Activated Sludge Respiration Inhibition test.
2 The results of the Activated Sludge Respiration Inhibition Test (ASRI) will determine which of the four biodegradation tests would be anticipated to 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, GLN 835 .3280 or (ii) Simulation Test

- Aerobic Sewage Treatment: A. Activated Sludge Units, GLN 835.3240, or (iii) the Porous Pot Test, GL N 835.3220 would be required. If the ASRI test 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 either 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 estuarine/marine, depending on which was most acutely sensitive

.

Page 14 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov


## 3 Human Health Risk Assessment

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

- PAD

. Additionally, t he Agency 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 Existing Toxicological Endpoints

The Agency 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 and valid scientific literature, will be considered in establishing the endpoints to be used in the registration review ri sk assessment. A dditional studies
, such as a 90

- day inhalation toxicity study and developmental toxicity study in non

- rodents are anticipated to be required for risk assessment based on the adverse effects observed in the oral studies and the currently reg istered

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) Study and Toxicological 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 )

LOAEL= 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 ( 45151902 )

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 Agency has not previously conducted a dietary (food and drinking water) exposure and risk assessment for 1,3

- PAD

. A dietary (food) exposure assessment is not required for 1,3

- PAD at this time because the registered uses are for non

- food

- use areas and are not expected to result in direct or indirect dietary (food) exposure.

Page 15 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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 Food

The Agency does not anticipate the need to conduct dietary exposure (food) assessments as part of the registration review process
, and r esidue chemistry data are not required at this time.



### 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 Agency cannot rule out the potentia l for 1,3

- PAD to enter drinking 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 thr ough a wastewater treatment plant (WW TP). Therefore, the Agency anticipates needing certain environmental fate data listed in Section 4 of this FWP . These data will be useful to determine whether, and to what extent, residues of 1,3

- PAD pass through a W WTP. The Agency 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, w hich 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. 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.



## 3.3 Occupational and Residential Exposures

The Agency 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

. 

### 3.3.1 Occupational Handler Exposure Occupational ha ndler 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 the 2005 occupational assessment ranged from 308

- 815 for low pressure spray and mop, w hich 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 Agency 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 fluids 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

Page 16 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

is used in closed systems for metalworking fluids a nd oil field uses and has a low vapor pressure (10

- 6 ), inhalation exposures are not expected. Thus, EPA anticipate s that there are no dermal and inhalation risks for 1,3

- PAD from these uses ; and therefore these exposures will not be evaluated for these two uses

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

.
Table 8

– Occupational Handler Exposure 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 Disinfectant 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 Intermediate Term



### 3.3.2 Occupational Post

- application No occupational post

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

. 

### 3.3.3 Residential Handler Exposures All 1,3

- PAD labels indicate products are only for institutional, 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 products 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 gallon) 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 the 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 to floors cleaned with disinfectant cleaning solutions

. Dermal Incidental Oral Short and Intermediate Term

Page 17 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov



## 3.4 Aggregate and Cumulative Exposure
3.4.1 Aggregate Exposures

The Agency anticipates the need to conduct the aggregate assessment. Upon a reevaluation and 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 ( drinking water ) exposures and residential exposures.



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

common mechanism of toxicity finding as to 1,3

- PAD and any other subs tances , 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 informat ion 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/non

- estuarine oil field wa ter 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 from 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 include sanitizer/disinfectants applied to hard surfaces and subsequently discharged down

- the

- drain from rinsing of mops/cloths used to wipe sanitizer/disinfectant from hard su rfaces. 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 habitats. When an assessment con cludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.

Based on the antimicro bial 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 Antimicrobial 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

Page 18 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

( 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 chem ical 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 Agency cannot determine the potential for 1,3

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

. Additional environmental fate information can be found in Appendix B.



### 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 potential 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 flood systems include: discharge via WWTP effluent to surface water; overflow from storage ponds to surface water; and leaching to ground water from uncased wells or unlined storage ponds. Anot her pathway is by use of 1,3

- PAD as a hard surface sanitizer/disinfectant 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 c hronic 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 endpoints selected for 1,3

- PAD are provided in Table 10

.

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 19 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Table 10

– Ecological Ef fects 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 45115310



### 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

- the

- Drain module of E

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

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

- PAD that is used in met alworking fluids and oil recovery 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 determine 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 to 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 down

- the

- drain assessment is used to determine potential upper bound exposures and risks to aquatic organisms from uses tha t are expected to result in discharges to domestic wastewater treatment plants and subsequently to surface water. When information on

Page 20 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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 organi sms 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 Releases module of E

- FAST. The use of this module requires additional input data that are not available and is beyond the sco pe of this preliminary risk assessment

. Environmental fate and ecotoxicity data requirement s that would be needed to perform a risk assessment for industrial uses are expected to be included in the generic data call

in (GDCI) based on the absence of this i nformation.
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 b ut 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 l iterature 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 existing 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 Research Laboratory's Mid

Continent Ecology Division.


## 5 Endocrine Disruptor Screening Program (ED SP)
As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotox icity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual matur ation, fertility, pregnancy rates, reproductive loss,

4 http://www.epa.gov/pesticides/science/ef ed/policy_guidance/team_authors/endangered_species_reregistration_work group/esa_evaluation_open_literature.htm Page 21 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision , for 1,3

- PAD , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. 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 thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by t he substance, and establish a dose

- response relationship between the dose and the E, A, or T effect.
Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins f or the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 5 and includes some pesticides scheduled for registration rev iew and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.
For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 6


## 6 Optional Label Changes

The Agency invites any label amendments that could be considered to eliminate the anticipated need for EPA to require certain data, reduce the possib ility that EPA’s planned risk assessments overestimate risk due to reliance on conservative assumptions, and/or improve label clarity.
Since the publication of the PWP, registrants have submitted amended labels to the Agency to clarify that products are intended for nonfood contact use only. As such, the Agency no longer anticipates the need to conduct a dietary (food) assessment during registration review

.
A DCI will be developed accor ding to the data needs listed under Table 1 and Section 2,

“ Anticipated Data Needs .” The Agency expects to issue the DCI by March of 2016.

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.
6 http://www.epa.gov/endo/ Page 22 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov


## 8 References

Lonza. Lonzabac 12 MSDS. http://bio.lonza.com/uploads/tx_mwaxmarketingmaterial/Lonza_ProductDataSheets_Lon zabac_12_PDS.pdf

MRID 45115304

. Sloan, R. (1999) Lonzabac 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 Po int Determination of Lonzabac 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 Number: 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 45115310

. Gallagher, S.; Grimes, J.; Beavers, J. ( 2000) Lonzabac 12: An Acute Oral 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}

MRID 45115312

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

- Hour Flow

Through Acute Toxicity Test with the Bluegill (Lepomis machrochirus): Lab Project Number: 289A

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

MRID 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}

MRID 45115327. Flack, I. (1996 ) P4198: Abiotic Degradation: Hydrolysis as a Function of pH: Lab Project Number: LZA 102/960267: 2651. Unpublished study prepared by Huntingdon Life Sciences Ltd. 20 p.

MRID 45151902

. Johnson, W. (2000) Subchronic Dermal Toxicity/Immunotoxicity Study with Lonzabac 12 in Rats: Lab Project Number: 1076 SN3. Unpublished study prepared by IIT Research Institute. 405 p. {OPPTS 870.7800}
Page 23 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

MRID 45151903. Barton, S. (1994) P4150: Developmental Toxicity Study in Rats: Lab Project Number: 490730: 2283. Unpublished st udy prepared by Inveresk Research International. 81 p. {OPPTS 870.3700}

MRID 46309706. Sarff, P. (1999) Corrosion Characteristics of Lonzabac 12. Project Number: 45065, SP/99004/A. Unpublished study prepared by ABC Laboratories, Inc. 15 p.

MRID 46332202. S loan, 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. ECOTOX User Guide: ECOTOXicology Database System. Version 3.0. Available: http://www.epa.gov/ecotox/
U.S. EPA 2005. Memorandum from S. Mostaghimi to Velma Noble. Subject: Application and Post

- application Exposure Assessment for Bis

- 3

- aminopropyl dodecylamine. D308675.
U.S. EPA 2005. Memorandum from S. Mostaghimi to Velma Noble. Subject: Application and Post

- application Exposure Assessment for Bis

- 3

- aminopropyl dodecylamine. D308675.

Page 24 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov 

# Appendix A T oxicology Profile

Acute Toxicity for Product Labeling

As listed in Table A 1 , 1,3

- P A D was found to be low toxic for both acute oral and dermal toxicity (Toxicity 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 A1

– 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 mg/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 (Limit Test) II 48980409 0.62 mg/ L < L C 50 < 2.0 mg/ L (Limit Test) III 870.2400/ Acute eye irritation

– rabbit 48980413 Slightly irritating III 48980414 Irritating II 870.2500/ Acute dermal irritation

– rabbit 4511531 6/7; 45 114705 Sever/c orrosive skin irritant I

870.2600/ Dermal sensitization

– g uinea p ig 4511531 8 No t 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 subchronic 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 oral and dermal toxicit ies . A route

- specific 90

- day inhalation toxicity 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 /sanitizer with “coarse mechanical sprayer” in the registration review 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, 360 and 500 mg/kg

- day for a period of 2 8 days

. 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
Page 25 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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 ≥ 360 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 preparati on, 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 administe red to Albino Wistar 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 perf oration and pleural 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 g roup

.
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 parameter s were not considered 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 gro ups 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 importan ce of these changes 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 with 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

.

Page 26 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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

- 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 i n 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 als o 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 i s 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 tudy.
(3) A histopatho logy 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 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 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 evaluation 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 significan t differences between the two assessments and similar results were observed in the kidneys, nasopharyngeal 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 pathologist noted that:
(i) The renal changes were indicative of nephrotoxicity, rather than an exacerbation of a spontaneous change, and presented moderate proximal tubula r changes characterized by 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

Page 27 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

severity. Group V recovery males demon strated 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 t reatment related.
(iii) The respiratory findings were also not completely characterized in the original report. The reviewer observed muco

- purulent exudate in the respiratory tract indicative of a pneumonitis, likely due to the inhalation of the copious n asal 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 th e histopathological re

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

- Wee k Recovery Period” (MRID 451519 01).

870.3250 90

- Day Dermal Toxicity

– 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 at 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 p eriod of 28 days for animals in Cohort I, and 14 weeks for animals in Cohort II

.
No treatment

- related 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 histopa thology 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 also 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

. Additionally, a significant increase in food consumption was noted in mid

- and high

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

Page 28 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

In Cohort II, increases in absolute white blood cells, absolute neutrophils, and absolute and relative 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 the 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 m ainly 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/day.
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 database for prenatal developmental toxicity is considered inadequate for the currently registered uses. The d evelopmental toxicity assessment for 1,3

- PAD is based on developmental stud ies in the rat (MRID s 45115322 and 45151903 ). A developmental toxicity study in non

- rodent species 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 150 (45.3 mg a.i.) mg/kg / day for a period 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

Page 29 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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 questi onable 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 salivation, with some brown staining, in most femal es 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 toxicity 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 guidelin e 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

- Dawley, 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 sig ns 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, significantly 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 nsi gnificant 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 was observ ed i n any of the treatment groups.
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

.
Page 30 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov 

## 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 Age ncy ’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 by 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 prior 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 (approximately 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 dyspnea, 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, decreased 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 showed 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.
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

.

Page 31 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov



## Chronic To xicity / Carcinogenicity Adequacy of D atabase for Chronic Toxicity/Carcinogenicity : The database for chronic toxicity and carcinogenicity is considered to be adequate for the currently registered uses. Assessment of chronic toxicity and carcinogenicity for 1,3

- PAD is based on a combined chronic toxicity and carcinogenicity study in rats ( MRIDs 48658501/02 ) in the Agency ’s hazard database

. No additional data are anticipated to be required.
(1) In a combined chronic toxicit y/ carcinogenicity stud y (MRID 48658501/02), groups of 10 male and 10 female CD rats were administered 0, 4, or 8 mg / kg b.w. / day of the N

- (3

- Aminopropyl) N

- Dodecylpropane

- 1,3

- Diamine (89.4% a.i.
, Batch # 20570

- MOl) in feed for 52 weeks; 20 animals per sex were also administered 20 mg/kg/day of the test compound for 52 weeks. Hematology
, clinical chemistry, organ weights measurements as well as gross and histopathology were performed.

Eight high dosed male animals treated with 20 mg/kg b

. w./day died prematurely. The body weight of the rats treated with 20 mg /kg b.w. / day was reduced up to 57% from test week 0 to 25 for male animals and by up to 25% from test week 0

- 51 for the female animals

. The body weight gain of the rats changed accordingly. The body weight at autopsy was reduce d in the males and females. The body weight, body weight gain, and body weight at autopsy were not influenced in the male and female rats treated with 4 or 8 mg / kg b.w. /day.

The food consumption of the animals treated with 20 mg /kg b.w ./ day was increased by up to 18% for the male rats in test weeks 39 t o 45 and by up to 20% for the females i n test weeks 31 to 51 caused by the severely reduced body weight.

Increased absolute kidney weights were noted in the females and decreased liver weights were noted in the males treated with the high dose of test substance

. The myeloied:erythroid ratio of the male animals treated with 20 mg / kg b.w ./ day was significant ly increased (Control 0

. 993:1
, 20 mg/kg 1.847:1).

The males treated with 8 mg/kg /day and animals of both sexes treated with 20 mg /kg/day sho wed a dose dependent increase of lympho

- histiocytic myocarditis. This finding was associated with degenerative c hanges of the myofibers in the heart

. The males treated with 8 or 20 mg /kg /day and the females of the high dose group showed an increase of lympho

- histiocytic infiltrations in the skeletal muscles. Degeneration of the skeletal muscles was noted in 2 intermediate dose males. Additionally, the animals treated with 8 or 20 mg / kg b.w ./ day showed a minimal to moderate increase in basophilic tubular cells and lympho

- histiocytic infiltration of the kidney

. Suppurative inflammation was observed in the prostate and mesenteric lymph nodes of the animals in 20 mg /kg b. w ./ day dose group compared to the control animals and the other treat ment groups. Granulomas wi t h central neutrophilic granulocytes were on ly noted in the mesenteric lymph node of male and female rats of the high dose group. The lungs of the male

Page 32 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

and female animals in the 8 or 20 mg /kg b.w./day dose groups showed an increased incidence of foci of foamy macrophages (alveolar histiocytosis) in the alveoles of the lungs.

The NOAEL was 4 mg /kg / day ; the LOAEL was 8 mg /kg / day , bas ed on the histopathology observed in the heart
, lymph node
, skeletal muscle
, and kidney.

This study is classified as Acceptable/Guideline

. ( 2 ) In a combined chronic toxicit y/ carcinogenicity stud y (MRID 48658501/02), N

- (3

- Aminoprop y l) N

- Dodec y l

- propane

- 1
, 3

- diamine (89.4% a.i.
, Batch # 20570

- MOl) was administered to groups of 50 male and 50 female CD rats in the feed at 0 (Group 1)
, 4 (Group 2) 8 (Group 3)
, or 20 / 15 / 12 (Group 4) mg /kg b.w. / da y for 104 weeks. The 20 / 15 / 12 m g/kg b.w. / da y was dosed as below.

The initi a l dose le v el of 20 mg/kg b.w ./ day of the high dose group was reduced to 15 mg/kg b.w ./ day as of test day 351 (test week 51, both genders) and further reduced to 12 mg/kg b.w. / day as of test da y 386 (test week 56
, males) and 407 (test week 59
, females). The dosing of the high dosed animals was discontinued from test day 431 (test week 62
, males) and test day 568 (test week 82
, females) onwards due to a high mortality.

There was no increases of neoplasms in dosed rats

. Non

- neoplastic histopathological lesions

were see n at 4 mg/k g/ day or higher dose levels. Non

- neopla s tic lesions were noted in the heart
, skeletal muscle
, kidney
, and lymph node (mesenteric) of male and female rats.

An increased mortality was seen in both males and females at 20/15/12 mg/kg b.w. / day
, when compared to the control or the 4 or 8 mg/kg / day animals

. In the high dose animals, males and females showed a body weight change of 69% and 73% ( of control ) for males and females, respectively, for weeks 53. No test compound

- related influence (<10%) was noted on the body weight gain of the animals treated with 4 or 8 mg /kg b.w ./ day from weeks 0

- 75 ; whereas, i n the female of the 8 mg / kg b.w./day dose group showed a decrease from weeks 0

- 103 to 82% of control.

Hematology changes were seen at 20 / 15112 mg / kg day when compared to the control and lower dose animal s. Male and female animals showed changes in the clinical biochemistry at 8 mg/kg/day vs. the controls.

The NOAEL was < 4 mg / kg / day (lowest tested dose [LTD]); the LOAEL was 4 mg /kg / day
, ba sed on the histopathology observed in the heart
, lymph node
, and skeletal muscle.

This study is classified as Acceptable/Guideline

. 

## 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

Page 33 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

mutagenicity studies have been submitted and reviewed 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

su mmaries of these studies are provided 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 wi th 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 classifi ed as Acceptable and satisfies the guideline 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 level s (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 a ssays, 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 sel ection 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 mutations 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.
This study is classified as Acceptable and satisfies the guideline 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 observed for any test concentration at any harvest time, with or without S9 activation. How ever, a significant dose

- depende nt increase of polyploid cells

Page 34 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

was observed after both 17 as well as 24 h ours + 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 w ere not used in the evaluation of the data and there are no recommended 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 in traperitoneal injection (i.p.) to 1,3

- PAD (purity of 90% a.i. ) dissolved 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 d ay 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:CD

- 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 sac rificed 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 aft er 24 hours, showed signs of hypertension of the back, hunched posture, 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 hou rs showed signs of hyperextension of the back, hunched posture, squinted 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 under the test conditions of the assay at both time periods

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

870.7800 Immunotoxicity Study
Adequacy of Database for Immunotoxicity: A subchronic dermal toxicity/immunotoxicity study in rats (MRID 45151902) is available in the Agency ’s hazard database . The Agenc y has reviewed the study and determined that the immunotoxicity portion of the 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 immunotoxi city portion of the study (Cohort I) is provided below.

Page 35 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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 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/I mmunotoxicity)

. Cohort I parameters consisted of observations, immunotoxicity, 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 sh owed 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 calculated.
This study is classified as Acceptable and meets the guideline requirements of 870.7800 for an Immunotoxicity Study. 

## Other Special Studies

There is one metabolism study (MRI D 45115326) and one in vitro percutaneous absorption study (MRID 46309705) in the Agency ’s hazard database. The Agency 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, metabolism, tissue distribution, and proportion of metabolites were investigated over a 120

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

- or sex

related diff erences 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 s ex 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 res ulted in approximately 0.2% gastrointestinal absorption regardless of sex. Low 14 C

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

- labeled test substance radioactivity in the plasma was generally below the limit of reli able measurement for both the 3 and 30 mg/kg doses. Peak concentrations (0.12 μg equiv./mL) were reported at 4 and 12 hours after low and high dose
Page 36 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

administration, respectively. The half

- life plasma concentrations after a 30 mg/kg dose were determined to b e 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 throughout the gastrointestinal tract and its contents. Low levels (qualitative data measured visually) of the test substance were present in ot her tissues, providing additional evidence for low oral absorption.
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). Six minor metabolites were detected in the f eces after both doses, although all were minor and individually represented 1%

- 3% of the administered doses. One of these 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 unsucce ssful.
In comparing this study to the guideline requirements for a toxicokinetic study (OPPTS 870.8500) in rats, the study would not satisfy the requirement that the highest dose did not produce any clinical indications of toxicity.

This short

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

870.7600 Dermal Penetration

In a non

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

- PAD (97.1% a.i., Batch No. KV 021704), and [ 14 C]

- 1,3

- PAD in the form of a hydrochloride salt (98.3% radiochemical purity, specific activity of 25.7 mCi/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 11 donor skin samples (200

- 500 μm thick stratum corneum) from 6 female human dono rs 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. The 1% (w/v) [ 14 C]

- 1,3

- PAD / 1,3

- PAD solution was poorly absorbed with dermal absorpt ion 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 Agency do es 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 chemical 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 A2 below

.

Page 37 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Table A2

– 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 870.3250 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.
Developmental/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) Developmenta l Toxicity LOAEL > 200 (60.4 mg a.i.) mg/kg/day (not established) 870.3700 Prenatal developmental in rodents

– Rat purity 30.2% 45151903 (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)

Page 38 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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

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

Chronic Toxicity/Carcinogenicity

870.4300

Combined Chronic Toxicity/Carcinogenicity

Purity 89.4% 48658501/02 (2010) Chronic Toxicity NOAEL =4 mg / kg / day Chronic Toxicity LOAEL = 8 mg / kg / day, based on the histopathology observed in the heart
, lymph node, skeletal muscle, and kidney ( degenerative changes of the myofibers [lympho

- histiocytic myocarditis] ; degeneration of the skeletal muscles [an increase of lympho

- histiocytic infiltrations] ; minimal to moderate increase in basophilic tubular cells and lympho

- histiocytic infiltration of the kidney ; suppurative inflammation in mesenteric lymph nodes [granulomas with central neutrophilic granulocytes] ).

There wa s no increases of neoplasms in dosed rats. Mutagenicity

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) Positive

870.5385 In vivo Mammalian Bone Marrow Micronucleus Assay

- Mouse purity 90% 46342601 (2004) Negative

Immunotoxicity

Page 39 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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

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 (1996) 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 radioactivity in the plasma was generally below the limit of reliable measurement for both the 3 and 30 mg/kg doses. Peak concentr ations (0.12 μg equiv./mL) were reported at 4 and 12 hours for 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. No diffe rences 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 a nd 10% males). One of these metabolites was identified as 1

- dodecylamine, the proposed biotransformation pathway. 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.
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 40 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Toxicology References

45114705 Moore, G. (2000) Primary Skin Irritation Test with Lonza Formulation LNZ

- 64 (in Rabbits): Lab Project Number: 8701: P326 TRS. Unpublished study prepared by Product Safety Labs. 25 p. {OPPTS 870.2500}

45115314 Jones , J. (1988) P4150: Acute Oral Toxicity in the Rat: Lab Project Number: 102/17: 0762. Unpublished study prepared by Safepharm Laboratories Ltd. 21 p. {OPPTS 870.1100}

45115315 Jones, J. (1988) P4150: Acute Dermal Toxicity (Limit Test) in the Rat: Lab Projec t Number: 102/48: 0761. Unpublished study prepared by Safepharm Laboratories Ltd. 14 p. {OPPTS 870.1200}

45115316 Jones, J. (1988) P4150: Acute Dermal Irritation/Corrosion Test in the Rabbit: Lab Project Number: 102/18: 0763. Unpublished study prepared by Safepharm Laboratories Ltd. 16 p. {OPPTS 870.2500}

45115317 Allen, D. (1994) P4198: Acute Dermal Irritation Test in the Rabbit: Lab Project Number: 102/177: 2438. Unpublished study prepared by Safepharm Laboratories Ltd. 16 p. {OPPTS 870.2500}

45115318 All an, S. (1996) P4150: Skin Sensitization in the Guinea Pig: Lab Project Number: LZA 129/953059/SS: 2574. Unpublished study prepared by Huntingdon Life Sciences Ltd. 24 p. {OPPTS 870.2600}

45115319 Korn, W. (1992) Final Report: A 4

- Week Oral Dose Range Findi ng Study in Rats with 0P4150: Lab Project Number: 20

- 04

- 0843

- 90: 1908. Unpublished study prepared by IBR Bioanalytisches Zentrum. 115 p. {OPPTS 870.3100}

45115320 Prentice, D. (1999) 90

- Day Oral Toxicity Study with P4150 in Rats Followed by a 4

- Week Recove ry Period (Lonza Report No. 1083): A Histophathological Review and Expert Opinion: Lab Project Number: 1083. Unpublished study prepared by PCS Consultants Ltd. 44 p. {OPPTS 870.3100}

45115322 Barton, S. (1993) P4150: Dose Range Finding Study in Rats Prelim inary to Teratogenicity Study: Lab Project Number: 490725: 2161. Unpublished study prepared by Inveresk Research International. 45 p. {OPPTS 870.3500}

45115323 Bosse, R. (1991) Final Report: In Vitro Mammalian Cytogenetic Test with P4150: Lab Project Numbe r: 95

- 86

- 2077/02

- 90: 1802. Unpublished study prepared by IBR Bioanalytisches Zentrum. 25 p. {OPPTS 870.5375}

45115324 Kennelly, J. (1988) Study to Determine the Ability of P4150 to Induce Mutation in Five Histidine

- Requiring Strains of Salmonella typhimuri um: Lab Project Number: LOB 11/S: 0765. Unpublished study prepared by Microtest Research Limited. 30 p. {OPPTS 870.5265}

Page 41 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

45115325 Bosse, R. (1991) Final Report: In Vitro Mammalian Cell Mutation Test P4150: Lab Project Number: 95

- 86

- 2077/02

- 90: 1801. Unpubl ished study prepared by IBR Bioanalytisches Zentrum. 28 p. {OPPTS 870.5300}

45115326 McEwen, A. (1996) P4198: Toxicokinetic Study in the Rat: Lab Project Number: LZA 103/961230: 2706. Unpublished study prepared by Huntingdon Life Sciences Ltd. 65 p. {OPPTS 870.8500}

45151901 Korn, W. (1992) Final Report: 90

- Day Oral Toxicity Study with P4150 in Rats Followed by a 4

- Week Recovery Period: Lab Project Number: 20

- 04

- 0843

- 90: 1083. Unpublished study prepared by IBR Bioanalytisches Zentrum. 539 p. {OPPTS 870.3100 }

45151902 Johnson, W. (2000) Subchronic Dermal Toxicity/Immunotoxicity Study with Lonzabac 12 in Rats: Lab Project Number: 1076 SN3. Unpublished study prepared by IIT Research Institute. 405 p. {OPPTS 870.7800}

45151903 Barton, S. (1994) P4150: Developmen tal Toxicity Study in Rats: Lab Project Number: 490730: 2283. Unpublished study prepared by Inveresk Research International. 81 p. {OPPTS 870.3700}

45151904 Barton, S. (1995) P4150: Two Generation Reproduction Study in Rats: Lab Project Number: 490924: 242 0. Unpublished study prepared by Inveresk Research International. 172 p. {OPPTS 870.3800}

46309705 Roper, C. (2003) The In Vitro Percutaneous Absorption of [Carbon

- 14]

- Lonzabac 12 Through Human Skin at an Incorporation Rate of 1 Percent (w/v) in Water. Pro ject Number: 23362, 204648. Unpublished study prepared by Inveresk Research International. 36 p.

46342601 Erexson, G. (2004) In Vivo Mouse Micronucleus Assay with Lonzabac 12: Amended Final Report. Project Number: 7483/101, 25872/0/455OECD. Unpublished stu dy prepared by Covance Laboratories, Inc. 58 p.

46603601 Merkel, D. (2005) Acute Dermal Toxicity Study in Rats with LNZ

- 64. Project Number: 17362, P322/TRS, 041215/7D. Unpublished study prepared by Product Safety Laboratories. 14 p.

46603602 Merkel, D. (20 05) LNZ

- 64: Dermal Sensitization Test in Guinea Pigs (Buehler Method). Project Number: P328/TRS, 16758, 041215/7D. Unpublished study prepared by Product Safety Laboratories. 26 p.

46603603 Merkel, D. (2005) Acute Inhalation Toxicity Study in Rats

- Limit Test. Project Number: P330/TRS, 17363, 041215/7D. Unpublished study prepared by Product Safety Laboratories. 26 p.

Page 42 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

47272201 Durando, J. (2007) Acute Inhalation Toxicity Study in Rats

- Limit Test with Lonzabac 12. Project Number: 22102, P330/TRS. Unpublishe d study prepared by Eurofins/Product Safety Laboratories. 25 p.

48658501 Hansen, B.; Leuschner, J. (2011) Combined Chronic Toxicity and Carcinogenicity Study of N

- (3

- aminopropyl)

- N

- dodecylpropane

- 1,3

- diamine by Dietary Administration to CD Rats. Part I: 10 4

- Week Carcinogenicity Study. Project Number: 4680 20570/06//PART/1/OCR. Unpublished study prepared by Laboratory of Pharmacology & Toxicology. 4798p.

48658502 Hansen, B.; Leuschner, J. (2010) Combined Chronic Toxicity and Carcinogenicity Study of N

- (3

- Aminopropyl)

- n

- dodecylpropane

- 1,3

- diamine by Dietary Administration to CD Rats. Project Number: 20570/06/OCR. Unpublished study prepared by Laboratory of Pharmacology & Toxicology. 1162p.

48980409 Bain, J. (2012) An Acute Toxicity Study of Sanitizing Wash N Walk by Inhalation Administration in Rats: Final Report. Project Number: 672427, 33695, 1200006CL6. Unpublished study prepared by Charles River Laboratories. 75p.

48980410 Lemoncelli, A. (2012) Delayed Contact Hypersensitivity in Hartley Guinea Pigs (Buehler Method) with Sanitizing Wash n Walk: Final Report. Project Number: 0424GE31/003, 1200006CL4. Unpublished study prepared by Calvert Preclinical Services, Inc. 59p.

48980413 Lemoncelli, A. (2012) Primary Eye Irritation Study in Rabbits with Sanitiz ing Wash N Walk Use

- Solution: Final Report. Project Number: 0421LE31/008, 1200006CL7. Unpublished study prepared by Calvert Preclinical Services, Inc. 57p.

48980414 Lemoncelli, A. (2012) Primary Eye Irritation Study in Rabbits with Sanitizing Wash N Walk: Final Report. Project Number: 0421LE31/007, 1200006CL1. Unpublished study prepared by Calvert Preclinical Services, Inc. 58p.

Page 43 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov 

# 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 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). While it was not included in the ATMD RED for alkyl trimethylene diami nes, 8

, 9 it is a diamine compound with similar structural, chemical 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, miscible 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 potential to create environmental exposure. The meta lworking 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 effluent water from WWTPs

.
A n a er obic 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 can create down

- the

- drain exposure from release of u sed 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 06 7313. Page 44 of 5 3Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Soil
Soil Leaching/Adsorption/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 flui ds 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 regist ered 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 usable data on anaerobic aquatic metabo lism 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 WWTPs 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 WWTPs where they could adversely affect microorganisms.

Table B1

– Summary of Chemical, Physical, and Environmental Fate Properties

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

- PAD Property OCSPP Guideline No. (unless stated) Value Citation

CAS No. None 2372

- 82

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

Page 45 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

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 stated) 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 stated) 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/kg 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 biodegradation 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 (mm 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 from 290

- 800 nm Page 46 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Environmental Fate and Transport References :

45115304 Sloan, R. (1999) Lonzabac 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

- 99010

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

45115308 Lonza, Inc.; Lewis and Harrison, LLC. (2000) Produ ct 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 st udy. 8 p. {OPPTS 830.7950}

45115327 Flack, I. (1996) P4198: Abiotic Degradation: Hydrolysis as a Function of pH: Lab Project Number: LZA 102/960267: 2651. Unpublished study prepared by Huntingdon Life Sciences Ltd. 20 p.

46309706 Sarff, P. (1999) Corrosion Characteristics of Lonzabac 12. Project Number: 45065, SP/99004/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: 06 5/002, 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.pdf

Page 47 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov 

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Organisms

Birds, acute oral

One available acute

- oral (LD50) study categorizes 1,3

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

Table C1 Avian Acute

- oral Toxicity

Test Species Test Material ( % ai) Toxicity Toxicity Category EPA Study ID
Northern bobwhite ( Colinus virginianus ) Lonzabac 12 (24.3%) LD 50 = 25 mg ai/kg bw Highly toxic 45115310 Supplemental 1

1 test material was not the TGAI 

### Toxicity to Aquatic Organisms

Freshwater Fish, acute and chronic
The available acute toxicity studies categorize 1,3

- PAD as being highly 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 r epeated 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/marine fish toxicity data are available

.
Table C2 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 45115311 Supplemental 2 Bluegill ( Lepomis macrochirus ) 95.2 (radio

- labeled) 96

- hr LC50 = 0.45 Highly toxic 45115312 Acceptable

1 adjusted for the purity of the test material
2 numerous guideline deficiencies, 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 48 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Freshwater Invertebrates, acute and chronic
The acute toxicity studies for the waterflea categorize s 1,3

- 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 the freshwater species is more sensitive than the estuarine/marine species for which data are not currently available

.
Table C3 Freshwater Invertebrates

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

Waterflea ( Daphnia 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. (850.1025 or 850.1055), and one additional invertebrate sp. (850.1035). C hronic toxicity testing with estuarine/marine organisms (850.1400, 850.135 0) would be needed only if the acute tests indicate that the estuarine/marine species are more sensitive than freshwater species

. Aquatic Plants
No toxicity data are available. To support the TGAI, two studies are anticipated as needed : a Tier II test w ith a vascular species (850.4400) and an algal toxicity Tier II test for green algae (850.4500). If the green algae 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 49 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Ecotoxicity References:

45115310 Gallagher, S.; Grimes, J.; Beavers, J. (2000) Lonzabac 12: An Acute Oral 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}

4 5115311 Ritt er, 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 machrochirus): 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 850.101 0}

Page 50 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov 

# Appendix D Screening Level Down

- the

Drain Analysis

No Down

- the

- Drain analysis was performed for 1,3

- PAD for this Final Work Plan (see section 4.3.2)

.

Page 51 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov 

# 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 E1

– Product Chemistry of 1,3

- Propanediamine,N1

- (3

- aminopropyl)

- N1

- dodecyl

Guideline Num bers 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 Impurities 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 amine

- 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) Setting 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 and 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 soluble 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 25oC

Page 52 of 53Docket Number EPA

- HQ

- OPP

- 2014

- 0406 www.regulations.gov

Product Chemistry R eferences :

Lonza

. Lonzabac 12 MSDS

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

MRID 45115304

. Sloan, R. (1999) Lonzabac 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 Lonzabac 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 Number: 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, 8 30.6317, 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. Project Num ber: 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.

Page 53 of 53