Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 2 of 48 TAED Registration Review Team

Human Health & Environmental Effects Srinivas Gowda James Breithaupt William Erickson Siroos Mostaghimi Timothy Dol e Zoe Cavinder Steven Malish

Risk Management SanYvette Williams Rose Kyprianou Karen Leavy

Office of General Counsel Philip RossDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 3 of 48 TERMS, ABBREVIATIONS AND SYMBOLS

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

atm

- m 3 /mole a tmospheric pressure

- cubic meter per mole BCF b ioconcentration f actor °C d egrees Celsius CaSO 4 c alcium s ulfate CaSO 3 c alcium s ulfite CAS Chemical Abstracts Service CCA c hromated c opper a rsenate CFR Code of Federal Regulations CHO Chinese h amster o vary CMA Chemical Manufact urers Association CO 2 c arbon dioxide COC c oncentration

- of

- c oncern cPAD c hronic p opulation a djusted d ose CS 2 c arbon disulfide DCI data call

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

- FAST Exposure and Fate Assessment Screening Tool EPI Suite Estimation Program Interface Suite
EPA Environmental Protection Agency FDA Food and Drug Administration FFDCA Feder al Food, Drug, and Cosmetic Act FGD f lue

- g as d esulfurization FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act
FWP Final Work Plan g/mol g rams per mole GLN guideline number
HPV h igh production v olume IDS Incident Data System
Koc o rganic carbon normalized soil

- water partition coefficient Kd s oil

- water partition coefficient
Kow o ctanol

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

- o bserved

- a dverse

- e ffect

- c oncentration LOEC l owest

- o bserved

- e ffect

- c oncentration LOAEL lowest

- observed

- adverse

- e ffect

- l evel Log K
ow l ogarithm of the octanol

- water partition coefficient

μg m icrogram ml/g m illiliter p er g ramDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 4 of 48 mg/kg m illigram p er k ilogram mg/kg/day m illigram p er k ilogram p er d ay mg/L m illigram p er l iter mm Hg m illimeter of mercury MOE m argin of e xposure MRID Master Record Identification Number
MRL m aximum r esidue l imit N/A n ot a pplicable

nm n anometers NOAEC no

- observed

- adverse

- effect

- c oncentration NOAEL n o

- o bserved

- a dverse

- e ffect

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

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

- 10 logarithm of the acid dissociation constant of a solution ppb p arts p er b illion

ppm p arts p er m illion
PWP Preliminary Work Plan QSAR q uantitative s tructure

- a ctivity r elationship
RED Rere gistration Eligibility Decision SAR s tructure a ctivity r elationship SF s afety f actor SSTS Section Seven Tracking System SO 2 s ulfur dioxide
TAED tetraacetyleneethylenediamine
TEP t ypical e nd

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

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 5 of 48 

### T able of Contents

1 Introduction

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

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

................................ ................................ ................................ ................. 9 1.3 Chemical Identification and Properties

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

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

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

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

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

................................ ................................ ................................ ......... 11 1.5.1 Recent/Pending Regulatory Actions

................................ ................................ ....... 11 1.5.2 Tolerance Information

................................ ................................ ............................ 11 1.5. 3 Design for the Environment

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

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

................................ ................................ ................................ ......... 12 1.6.2 Ecologic al

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

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

................................ ................................ ........................... 14 3. 1 Toxicological Endpoints

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

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

................................ ................................ ................................ ........................ 15 3.2.2 Drinking Water

................................ ................................ ................................ ....... 15 3.3 Occupational and Residential Exposures

................................ ................................ ....... 15 3.3.1 Occupational Exposures

................................ ................................ .......................... 15 3.3.2 Residential Exposures

................................ ................................ ................................ .. 16 3.4 Aggregate and Cumulative Exposure

................................ ................................ ............. 16 3.4.1 Aggregate Exposures

................................ ................................ .............................. 16 3.4.2 Cumulative Exposures

................................ ................................ ............................ 16 4 Environmental Risk Assessment

................................ ................................ ........................... 17 4.1 Environmental Fate Assessment

................................ ................................ .................... 17 4.1.1 Persistence in Water and Sediment

................................ ................................ ......... 18 4.1.2 Persistence in Soil

................................ ................................ ................................ ... 18 4.1.3 Persistence in Air

................................ ................................ ................................ .... 19 4.1.4 Pe rsistence in WWTP

................................ ................................ ............................. 19 4.1.5 Water Quality

................................ ................................ ................................ .......... 19 4.2 Environmental Exposure Pathways

................................ ................................ ................ 19 4.3 Ecological Effects Assessment

................................ ................................ ....................... 20 4.3.1 Mechanism of Action

................................ ................................ .............................. 20 4.3.2 Measures of Effect (Ecotoxicology Endpoints)

................................ ...................... 20 4.4 Exposure Analysis Plan

................................ ................................ ................................ .. 21 4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

................................ ............ 21 4.5 Effects Analysis Plan

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

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

................................ ................................ ................................ ........ 22
7 Guidance for Commenters

................................ ................................ ................................ .... 22 7.1 Preliminary Work Plan

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

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 6 of 48 7.1.1 Trade Irritants

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

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

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

................................ ................................ ............. 23 7.1.5 Additional Information

................................ ................................ ........................... 24 8 Ne xt Steps

................................ ................................ ................................ ............................. 24 9 References

................................ ................................ ................................ ............................. 25

Appendix A T oxicology Profile

................................ ................................ ............................... 26 Appendix B Environmental Fate

................................ ................................ ............................. 35 Ap pendix C Ecotoxicology Profile

................................ ................................ .......................... 44 Appendix D Product Chemistry

................................ ................................ ............................... 47

List of Tables Table 1

– Summary of Anticipated Risk Assessments and Data Needs: TAED

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

– Anticipated Registration Review Schedule

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

– Chemical Identification of Tetraacetylethylenediamine (TAED)

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

– Physical

- Chemical and Environmental Fate Properties for Tetraacetylethylenediamine

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

– Summary of TAED Registered Uses

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

– Studies Anticipated as Needed for the Registration Review of TAED and DAED

..... 1 3 Table 7

– Occupational Exposure Scenarios for TAED

................................ ............................... 16 Table 8

– Residential Exposure Scenarios for TAED

................................ ................................ .. 16 Table 9

– Available Ecological Effects Endpoints for TAE D

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

List of Figures
No neDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 7 of 48 

## 1 Introduction

This document is the United States Environmental Protection Agency’s ( USEPA, EPA or “the
A gency”) Preliminary Work Plan (PWP) for tetraacetyleneethylenediamine (TAED) . The PWP document explains what EPA's Office of Pesticide Programs (OPP) knows about TAED

, 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 TAED review.

The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, by sharing this information in the do cket, to inform the public of what it knows about TAED and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on TAED. The Agency encourages all interested stakeholders to review the PWP and to provide comments and additional information that will help the Agency’s decision

- making process for this chemical.



## 1.1 Statutory and Regulatory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United States generally must be registered by the 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 environmen t. 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 safe ly. Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/

.
The Agency is implementing the registration review program pursuant to Section 3(g) of the Feder al Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 CF R 155 .40. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state what it knows about the pestic ide and what additional risk analyses and data or information it believes are needed to make a registration review decision. After reviewing and responding to comments and data received in the docket during this initial comment period, the Agency will deve lop and commit to a F inal W ork P lan (FWP) and anticipated schedule for the TAED Case.

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

- HQ

- OPP

- 20 13

- 0 6 08

. Tables 1 and 2 below summarize the issues relevant to this registration review case and the anticipated registration review schedule.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 8 of 48 Table 1

– Summary of Anticipated Risk Assessments and Data Needs : TAED

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 None None None

Dietary (drinking water) Yes 1 None New Developmental Toxicity

– Rabbit Reproductive Toxicity

Immuno Toxicity

Occupational Handler Yes 1 None New Indoor Exposure Data

– Dermal Indoor Exposure Data

– Inhalation Developmental Toxicity

– Rabbit Reproductive Toxicity

Immuno Toxicity

Residential Handler No None None None

Residental Post Application

- Incidental Oral and Dermal Yes 1 None New Textile Leaching Study Developmental Toxicity

– Rabbit Reproductive Toxicity

Immuno Toxicity

Aggregate Yes 1 None N ew Developmental Toxicity

– Rabbit Reproductive Toxicity

Immuno Toxicity

Cumulative No None None None

Tolerance Review No None None None

Ecological No None N one Green algae toxicity (for product labeling)

Environmental Fate Yes None New Aquatic exposure

1

. These assessments will be needed if endpoints are selected from the anticipated developmental, reproductive and immunotoxicity studies

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

- 03 2014

- 03

- 26
Close Public Comment Period 2014

- 05 Phase 2: Case Development
Issue Final Work Plan 2014

- 09
Issue Data Call

- In (DCI) 2015

- 09
Receive Data to be Considered in Risk Assessment 201 7

- 09 Open 30

- Day Public Comment Period for Preliminary Risk Assessment(s) 201 9

- 03
Close Public Comment Period 201 9

- 0 4 Phase 3: Registration Review Decision and Implementation Open 60

- Day Public Comment Period for Pro posed Decision 2019

- 0 9
Close Public Comment Period 2019

- 11
Issue Final Decision 20 20

- 03 Begin Post

- Decision Followup 2020 Total (years) 6Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 9 of 48 * The anticipated schedule will be revised as necessary ( e.g ., need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case).



## 1.2 Case Overview

The docket for the TAED c ase (Case #5105 ) has been established at http://www.regulations.gov in docket number EPA

- HQ

- OPP

- 2013

- 0608

.



## 1.3 Chemical Identification and Properties

Table 3 presents the active ingredient to be assessed in c ase 5105 : t etraacetylethylenediamine (PC Code 004115 ). When activated using an oxygen activator in the presence of water, TAED undergoes rapid perhydrolysis to yield peroxyacetic acid , which will be assessed under it’s own

case, and hydrogen peroxide and finally degrades to N,N

- Diacetylethyenediamine (DAED).

Table 3

– Chemical Identification of Tetraacetylethylenediamine (TAED)

Chemical Name Tetraacetylethylenediamine (TAED)

Chemical Classification Aliphatic amide

PC Code 004115

CAS Number 10543

- 57

- 4

Molecular Formula C 10 H 16 N 2 O 4 Molecular Weight (grams/mole) 228.25

Purity >99.95%

Molecular Structure

The t etraacetylethylenediamine product chemistry information relative to risk assessment is summarized in Table 4 and Appendix D

.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 10 of 48 Table 4

– Physical

- Chemical and Environmental Fate Properties for Tetraacetylethylenediamine

Guideline No. Parameter Tetraacetylethylenediamine

Physical/Chemical Properties

830.7000 pH 5 (20 o C, 1g/L) 5 (3% solution)

TAED has a UV/VIS absorption maximum at 214 nm
147°C + 1°C Not applicable to this product because it is a solid at room temperature Bulk density at 20 ° C is 430

- 520g/L Not applicable because TAED has no dissociable groups. Log Po/w: −0.06 2 g/100 ml at 20°C (20 g/L)
1.48 x 10 - 8 mm Hg 25 °C (EPI Suite v 4.1) 830.7050 UV/Visible Absorption

830.7200 Melting point ( o C)

830.7220 Boiling point ( o C)

830.7300 Density

830.7370 Dissociation constant (pKa)

830.7550 Octanol

- water partition coefficient
at 25 o C (Log K
ow )

830.7840 Solubility in water

830.7950 Vapor pressure (mmHg)

atm

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



## 1.4 Use/Usage Description

1.4.1 Registrations

There are two EPA

- registered end use products (EPA Reg

. N os. 1043

- 125 and 16930

- 5) that contain TAED as an active ingredient (a.i.). EPA Reg . No. 1043

- 125 contains 61.6 % TAED and EPA Reg . No. 16930

- 5 contains 11.9% TAED

.
EPA Reg . No. 1043

- 125 is Part A of a two part system this is mixed with Part B (EPA Reg. No. 1043

- 124 which contains 1.0 percent hydrogen peroxide) to create an end use hard surface disinfectant solution which

, according to the label, contains approximately 0.085 percent peroxyacetic acid and 1.0 percent hydrogen peroxide.

EPA Reg . No. 16930

- 5 is a solid formulation that contains TAED and another a.i. ( sodium percarbon ate )

. It is packaged in a capsule which is loaded into institutional and commercial laundry machines

. The label states: “When activated in the presence of water, this product will generate hydrogen peroxide and peroxyacetic acid to provide disinfectant a nd bleaching actions.” Hydrogen peroxide and peroxyacetic acid will be assessed under separate case s

.



### 1.4.2 Summary of Registered Uses

Table 5 presents a summary of the registered uses of TAED that will be assessed in this registration review

.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 11 of 48 Table 5

– Summary of TAED Registered Uses

Use Application Method Application Rate

Commercial Institutional and Industrial Premises and Equipment

Laundry (commercial) Washing Machine 111 ppm ai A

Medical/Dental/Veterinary Premises and Equipment

Hard surface disinfectant on floors, walls, counters, bedrails, doorknobs, and bathroom fixtures. Mop, wipe

, sponge C 0.085 percent perox y acetic acid B

Preclean and decontaminate c ritical or semi

- critical medical devices prior to high level disinfection or sterilization. I mmersion 0.085 percent perox y acetic acid B

A. Based on the label application rate of 3 oz EPA Reg. N o. 16930

- 5 per 24 gallons wash water. B. When the TAED product Part A ( EPA Reg. No. 1043

- 125) is added to part B ( EPA Reg. No. 1043

- 124). C. The label only mentions these methods of application. The label does not mention spray application.


### 1.4.3 Usage Information
Uses (Not Subject to EPA Registration)

According to the Household Products Database of National Library of Medicine, as of 1/02/2014, there are 13 non

- pesticidal household produc ts that contain TAED. These products include dishwashing detergents

. According to HERA (2002), 61,000 tons w ere consumed in the household detergents in the European Union in 2000.



## 1.5 Regulatory Histor y
Registered products containing TAED date back to 19 6 8

. In 201 2

, a new registration was approved , with a variety of uses as outlined in table 5.



### 1.5.1 Recent/Pending Regulatory Actions
There is one pending registration action in BPPD ( Bio pesticides and Pollution Prevention Division) that is currently under review.



### 1.5.2 Tolerance Information
There is no US EPA tolerance or tolerance exemption for TAED or its final degradation product
DAED because there are no food or feed uses

.



### 1.5.3 Design for the Environment
TAED has been approved by the EPA’s Design for the Environment (DfE) program in the category of “Oxidants and oxidant stabilizers.” The DfE program allow s products that have undergone rigorous EPA review based on stringent DfE criteria to bear a DfE logo on the label. As an approved Safer Chemical Ingredient for use in DfE

- labeled products, TAED has been “verified to be of low concern based on experimental and modeled data .” The verification category is the safest possible for its functional use (green c ircle) and meets the criteria of the DfE Safer Product Labeling Program. The l ink to access TAED on the DfE list of Oxidants and oxidant stabilizers and criteria is : http://www.epa.gov/dfe/saferingredients.htm

.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 12 of 48 

## 1.6 Incidents

1.6.1 Human Health

As of 01/03/2014, th ere are no TAED human poisoning incidents listed in the OPP’s Incident Data System for the time period from 10/24/05 to 3/18/14.



### 1.6.2 Ecological
There are no TAED fish or wildlife poisoning incidents in OPP’s Incident Data System

. 

## 2 A nticipated Data Needs

Table 6 presents a summary of the studies anticipated as being needed to support this registration
review. The Agency is currently evaluating the human health hazard database and whether any of the studies listed in Table 6 can be waived, as appropriate. The Agency will also consider any additional information or waiver requests from the registrant for the studies anticipated as being needed provided that such waivers include a valid rationale of how the registration review could
be conducted without the studies.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 13 of 48 Table 6

– Studies Anticipated as Needed for the Registration Review of TAED and DAED

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

Requirement Applicable Exposure Scenario

Studies Anticipated to be Required through the Registration Review DCI

850.4500 Algal toxicity

- green algae TGAI 24 Precautionary labeling All NA

835.4300 Aerobic aquatic metabolism Parent and DAED degradate 24 Drinking water and ecological exposure Hard surface disinfectant and washing machine use Oral exposure to drinking water and to aquatic organisms

. See footnote 4.

870.3700 Prenatal Developmental Toxicity

- Rabbit TGAI 24 Dietary (Drinking Water) Occupational Handler Residential Post Application Hard surface disinfectant and washing machine use See footnotes 1,2,3.

870.3800 Reproduction and Fertility Effects TGAI 24 Dietary (Drinking Water) Occupational Handler Residential Post Application Hard surface disinfectant and washing machine use See footnotes 1,2,3.

870.7800 Immunotoxicity TGAI 24 Dietary (Drinking Water) Occupational Handler Residential Post Application Hard surface disinfectant and washing machine use See footnotes 1 ,2,3.

875.1200 Indoor Exposure

– Dermal TGAI or surrogate 24 Occupational Handler Hard surface disinfectant See footnote 2.

875.1400 Indoor Exposure

- Inhalation TGAI or surrogate 24 Occupational Handler Hard surface disinfectant See footnote 2.

None Textile Leaching TGAI 24 Residential Post Application Washing Machine See footnote 3.

1 Dietary exposure scenarios include oral exposure to drinking water.

2 Occupational handler scenarios include dermal and inhalation exposure during hard surface disinfection using mops and wipes if toxicological endpoints are selected

. 3 Residential post application scenarios include dermal and incidental oral exposure to laundered textiles

. 4 TAED and its degradates have the potential to reach surface water. TAED and its degradates are water soluble and are likely to be present in surface water in the presence of sediment. Aerobic aquatic metabolism represents the dissipation of a compound in the water column of a lake or stream.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 14 of 48 

## 3 Human Health Risk Assessment

The human health database lacks three studies that are required per 40 CFR Section 158 Subpart W. These studies include the following:

• 870.3700

- Prenatal Developmental Toxicity (Rabbit)

• 870.3800

- Reproduction and Fertility Effects

• 870.7800

- Immunotoxicity

Based on the existing database which indicates low toxicity via dermal or inhalation exposure

, EPA did not previously conduct human health risk assessments for dermal or inhalation

exp osures to TAED or the degradate DAED ; however, this may change depending upon the outcome of the anticipated studies listed above

. In addition

, it may be necessary to assess incidental oral exposures to treated laundry and dietary exposures from drinking water because these exposures were not assessed previously.

The toxicological information for TAED was last reviewed in a n EPA Memorandum of April 20, 2005 by the Antimicrobials Division Toxicology Endpoint Selection Committee (ADTC). This

memo was written to evaluate the proposed new use of TAED as a laundry sanitizer. The ADTC recognized that there would be dermal and inhalation exposures from occupational use of TAED

, as well as incidental oral exposures from post

- application exposures in clothin g containing residues of TAED or DAED. Due to a lack of information on the toxicity of DAED, the ADTC concluded that in the absence of data, a metabolism study would be needed in order to determine the nature of the chemical exposure to mammalian organisms in vivo. This data is provided in summary form within the HERA document (HERA, 2002) and, while not formally reviewed by the Antimicrobials Division, indicates that there is significant conversion of TAED to DAED in vivo. While the data will need to be formally reviewed, the available data summary suggests that the toxic responses observed in the studies conducted with TAED may be the result of exposure to TAED and/or DAED, and separate studies with DAED would not be required

.
With respect to the need for a TAED dermal and inhalation endpoint to address occupational use as well as post

- application exposures that might occur (including infants and children), the ADTC noted from review of the toxicity data that the dose

- response for TAED is shallow and th e effect levels at which adverse effects are noted are relatively high (in some cases at or above limit doses). In addition, there is no evidence of susceptibility following exposure to TAED from the available developmental toxicity data. The nature of t he response itself (hepatocellular hypertrophy) is not considered by the ADTC to be an actual adverse effect, but a biological response. Therefore, the ADTC concluded that no endpoints are needed for dermal and inhalation exposures to TAED as would occur from the proposed uses of this chemical. The Agency will also consider any additional information or waiver requests from the registrant for the studies anticipated as being needed provided that such waivers include a valid rationale of how the registratio n review could be conducted without the studies.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 15 of 48 No additional toxicological studies have been submitted to EPA and no additional studies have been published in the literature since the ADTC review

. A summary of the toxicology studies for TAED is include d in Appendix A.

EPA does not anticipate the need to conduct human health risk assessments within this case for the hydrogen peroxide or peroxyacetic acid generated by TAED because these chemicals are being addressed as separate registration review cases.



## 3.1 Toxicological Endpoints

As discussed above, toxicological endpoints were determined to not be needed for dermal and inhalation exposures to TAED based on a 2005 review by the ADTC . T his conclusion might change ; however, if endpoints are selected from the anticipated toxicity studies. In addition

, it

may be necessary to select endpoints to assess incidental oral exposure s and drinking water

exposures because th ese exposure s w ere not assessed previously.



## 3.2 Dietary Exposure

The agency may need to conduct a dietary (drinking water) exposure assessment for TAED depending upon the outcome of the anticipated toxicity studies. A dditional residue chemistry data for TAED are not anticipated to be needed

.



### 3.2.1 Food

There are no direct or indirect food uses fo r TAED. Therefore, EPA does not anticipate the need to conduct a dietary (food) risk assessment.



### 3.2.2 Drinking Water
The agency has not conducted a drinking water assessment for TAED in the past. There are no direct drinking water uses for TAED, however, approv ed use as a commercial laundry detergent could potentially result in TAED being discharged into waste water and subsequently running off into surface water. Both of these exposure routes may potentially lead to indirect contamination

to human drinking water. B ased on the environmental fate assessment, TAED undergoes rapid perhydrolysis to yield peroxyacetic acid and hydrogen peroxide and finally degrades to DAED and is therefore unlikely to result in exposure to TAED.

If endpoints are selecte d from the anticipated toxicity studies, t he risks to human health from exposure to the final degradation product DAED in drinking water will need to be assessed

.



## 3.3 Occupational and Residential Exposures

3.3.1 Occupational Exposures
Occupational exposures are not anticipated for the commercial laundry use because the product is packaged as a capsule that is loaded into the washing machines. Occupational handler

exposures may occu r, h owever, for the hard surface disinfectant use in medical, dental and veterinary p remises and equipment

. If endpoints are selected from the anticipated toxicityDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 16 of 48 studies, these exposures will need to be assessed during registration review. The occupational exposure scenario is listed in Table 7

.

Table 7

– Occup ational Exposure Scenarios for TAED

Handler Scenario Exposure Route(s) Duration

Hard surface disinfection using mop s or wipe s. Dermal Inhalation Intermediate
Term

Occupational post application exposures are not anticipated for the existing uses of TAED (hydrogen peroxide is being assessed in a separate case)

. 

### 3.3.2 Residential Exposures

Residential handler exposures are not anticipated for TAED because TAED is used only in institutional and industrial laundries and medical/dental/veterinary faciliti es.

Although TAED is registered only for use in institutional and industrial laundries, r esidential post application exposures may occur if TAED laund ered items are used in a residential environment. If endpoints are selected from the anticipated toxicity studies, these exposures will need to be assessed during registration review. The residential exposure scenarios are listed in Table 8

.

Table 8

– Residential Exposure Scenarios for T AED

Scenario Exposure Route(s) Durat ion Adults wearing TAED laundered textiles Dermal Intermediate Term

Toddlers wearing or mouthing TAED laundered textiles Dermal Incidental Oral Intermediate Term



## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures
If endpoints are selected from the anticipated toxicity studies , then it will be necessary to assess aggregate exposures to TAED

.



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

, and any other substances and TAED 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 TAED has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/

.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 17 of 48 

## 4 Environmental Risk Assessment

The Agency has not previously conducted a n environmental risk assessment for the antimicrobial uses of TAED. Because TAED is transformed into peroxyacetic acid and hydrogen peroxide prior to or during application, any material going down the drain into wastewater treatment plants will be those moieties and their tra nsformation products. Both peroxyacetic acid and hydrogen peroxide are active ingredients in registered antimicrobial products that will be addressed separately in Registration Review. The degradate DAED also will be present when
TAED is transformed. A E uropean risk assessment 1 indicates that at least 97% of TAED and DAED would be removed during sewage plant treatment. Along with a limited data set indicating little if any toxicity to organisms in the water column, minimal risks were predicted
for either TAED or DAED in the aquatic environment in Europe. Because the amount of TAED produced annually in the U.S. is low (about 10,000 kg) and its use (laundries, medical, dental, veterinary medical premises) would be widespread geographically and temporally dur ing the year, the amount of either TAED or DAED entering the aquatic environment via waste water treatment plant discharges is likely to be minimal.



## 4.1 Environmental Fate Assessment

The Agency has not previously conducted a risk assessment that supports a c omplete endangered species determination for TAED. The ecological risk assessment planned during registration review will allow the agency to determine whether each use of TAED has 'no effect' or 'may affect' federally listed threatened or endangered spec ies (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical habitat, the agency will consult with the U.S. Fish and Wildlife Service and/or Nationa l Marine Fisheries Services (the Services), as appropriate.

The Agency will conduct an environmental fate assessment for TAED based on the current uses in industrial and institutional laundry facilities and hard, non

- porous surfaces in healthcare faciliti es, hospitals, medical, and dental offices. It serves as a bleach activator and reacts in aqueous solutions in the presence of an oxygen activator , such as sodium percarbonate, to form the DAED degradate, hydrogen peroxide and peracetic acid using the per hydrolysis reaction

. 2 Both peroxyacetic acid and hydrogen peroxide are highly

- reactive and degrade rapidly.

Guideline environmental fate data that address metabolism or transport of TAED in the terrestrial or aquatic environment have not been submitted to the Agency for TAED or its degradates. Although no data have been submitted, TAED and its degradates

, TriAE D (transient degradate) and DAED (terminal non

- volatile degradate)

, a re expected to partition to water in the presence of sludge based on a log Kow of

- 0.06. 3 Several studies are present in the literature

1 HERA. 2002. Tetraacetylethylenediamine (TAED) (CAS 10543

- 57

- 4). Human & Environmental Risk Assessment on ingredients of European household cleaning products. December, 2002.

2 Reaction in water to release peroxyacetic acid and hydrogen peroxide

3 MRID 45299701Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 18 of 48 and in the HERA document. 4 The studies listed in the HERA document have not been formally

reviewed by the Agency, but they indicate that TAED is readily biodegradable 5 and highly removed in the activated sludge of a WWTP based on a 97 percent removal rate in a porous pot

test. 6 The appropriate studies in the HERA document will be formally reviewed by the Agency before a final risk assessment. The Agency also has not received data on aerobic aquatic metabolism of parent TAED or the degradate DAED, which can reach surface water if they pas s through a WW TP.

Parent TAED is miscible in water (20 g/L) 7 and its sequential degradates TriAED and DAED are expected to have similar water solubility based on structural similarity. TAED (TGAI) slowly degraded by abiotic hydrolysis at pH 7 and 15 o C with a half

- lif e of 40 days and the DAED degradate was shown to be stable and not degrade. 8 However, in a washing machine study using a formulated product which includes oxygen , TAED appears to degrade rapidly to form the degradate DAED at 30, 40, and 60 o C 9 which represe nts cold, warm, and hot water temperatures, respectively. 10 The washing machine study, which is more environmentally

- relevant than the abiotic hydrolysis study, has not been formally reviewed . It will be reviewed prior to conducting the risk assessment. T he only detectable residue from the water in the washing machine was the DAED degradate. Appendix B contains additional information on the environmental fate of TAED and its degradation products.



### 4.1.1 Persistence in Water and Sediment

Parent TAED is miscible in water (20 g/L) 11 and its degradates

, TriAED and DAED

, are expected to have similar water solubility based on structural similarity. The primary residue to which aquatic organisms are likely to be exposed is the DAED molecule 12

, which is expected to partition to water in the presence of sediment based on the log Kow of

- 0.06 for parent TAED 13

.



### 4.1.2 Persistence in Soil
When used according to the label, TAED is not expected to reach soil because it will not be sorbed to biosolids based on the log Kow o f

- 0.06. 14 The registrant s ha ve not submitted any guideline studies on aerobic soil metabolism (OCSPP 835.4100) and anaerobic soil metabolism (OCSPP 835.4200) to determine the persistence of parent TAED and formation and decline of TriAED and DAED in soil. Because TAED will degrade to release hydrogen peroxide, therefore

, not expected to reach soil from the current uses, soil metabolism data are not anticipated to be required. The Agency also has not received and reviewed any guideline data (OCSPP 835.1230)

4 Human & Environmental Risk Assessment, http://www.heraproject.com/files/2

- F

- 04

- HERA%20TAED%20full%20web%20wd.pdf

5 OECD 301E data, IUCLID 2000, Proctor & Gamble Internal Data 1976 and 1978

6 Clariant, 2002

7 MRID 45299701

8 MRID 46335801

9 MRID 46335802, study not reviewed

10 http://housekeeping.about.com/od/laundry/a/laundry_h20temp.htm

11 MRID 45299701

12 MRIDs 46335801 (hydrolysis), 46335802 (wash water study)

13 MRID 45299701

14 MRID 45299701Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 19 of 48 on sorption of TAED to soil. However, two un reviewed studies in the HERA document indicate that TAED and DAED are expected to have minimal sorption to soil, based on Koc values for TAED and the degradate DAED of 15

- 80 and 25 L/kg, respectively. 15 These soi l sorption studies will be reviewed by the Agency prior to conducting a risk assessment.



### 4.1.3 Persistence in Air

TAED is miscible in water with a water solubility of 20 g/l and is not expected to volatilize from water. Therefore, partitioning from water into air is not likely for TAED

.



### 4.1.4 Persistence in WWTP
TAED and its degradates

, TriAED and DAED

, are miscible in water 16 and are expected to partition to water in the presence of sludge based on a log Kow of

- 0.06. 17 The Agency has not received any guideli ne studies for the biodegradation of TAED, but several studies are present in the literature and in the HERA document. 18 The studies listed in the HERA document have not been formally reviewed by the Agency, but they indicate that TAED and DAED are readily biodegradable 19 and highly removed in the activated sludge of a WWTP based on a 97 % removal rate in a porous pot test. 20 The Agency will formally review these studies prior to conducting a risk assessment.



### 4.1.5 Water Quality

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

. 21 In addition, Total Maximum Daily Loads (TMDL s ) have not been developed for TAED

. 22 More information on impaired water bodies and TMDLs can be found at EPA’s w ebsite

. 23



## 4.2 Environmental Exposure Pathways

Assuming that any relevant exposure occurs, aquatic organisms potentially at risk include those inhabiting water bodies adjacent to or downstream from waste water treatment plants. Water bodies might include impounded bodies (e. g., ponds, lakes

, reservoirs ) or flowing waterways (e.

g., streams

, rivers ) . For uses in coastal areas, aquatic habitat also includes marine ecosystems

, including estuari es. A quatic organisms potentially exposed include fish, invertebrates, aquatic stages of amphibians , and aquatic and semi

- aquatic plants. For aquatic animals, the major route of exposure to TAED or DAED is considered to be uptake via the respiratory surf ace (gills) or

15 AISE, 1992 and Shell, 20 00

16 MRID 45299701

17 MRID 45299701

18 Human & Environmental Risk Assessment, http://www.heraproject.com/files/2

- F

- 04

- HERA%20TAED%20full%20web%20wd.pdf

19 OECD 301E data, IUCLID 2000, Proctor & Gamble Internal Data 1976 and 1978

20 Clariant, 2002

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

22 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant _group_name=PESTICIDES

23 http://www.epa.gov/owow/tmdl/Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 20 of 48 the integument from surface water that has res idues . For aq uatic plants, the major route of exposure is considered to be uptake from surface water.



## 4.3 Ecological Effects Assessment

Ecological effects data are used as measures of direct and ind irect effects to aquatic and terrestrial organisms

. Acute and chronic toxicity data from registrant

- submitted studies conducted in accordance with the 850 OCSSP Harmonized Test Guidelines typically are used to evaluate the potential direct and indirect eff ects of a pesticide and its transformation products to plants and animals

. Relevant data from the open literature also may be used to evaluate potential direct and indirect effects

. As explained below, the agency anticipates calling in data for algal toxicity for labeling purposes. No ecological risk assessment is planned for TAED per se, since the degradates are hydrogen peroxide and peracetic acid which will be evaluated in their own

cases.



### 4.3.1 Mechanism of Action
The main antimicrobial activity occurs after TAED is activated to produce peroxyacetic acid and hydrogen peroxide. These transformation products are strong oxidizing agents that disinfect with corrosive action.



### 4.3.2 Measures of E ffect (Ecotoxicology Endpoints)

E cotoxicity endpoint s are used as measures of effects to assess acute and chronic hazards and risks to aquatic and terrestrial organisms. Because TAED is not expected to occur in the environment when used as directed on the product labels, only the basic four ecotoxicity studies required for all antimicrobial active ingredients are needed for TAED. Th ree of the studies have been submitted . O nly one of studies

— algal toxicity, green algae

— is anticipated to be required. Thos e studies are used to determine if precautionary label statements are needed and to have a basic data set in case of a spill or other unintended environmental accident . The four studies are as follows:

• 850.2100 Avian acute Oral Toxicity Test • 850 .1075 Fish Acute Toxicity Test, Freshwater • 850.1010 Aquatic Invertebrate Acute Toxicity Test, Freshwater • 850.4500 Algal Toxicity, Green Algae

The three submitted ecotoxicity studies categorize TAED as being practically nontoxic to birds, fish, and aquatic invertebrates. More information on these studies is found in Appendix C. The green algae toxicity study is a data gap. The Agency has no ecotoxicity data for D AED but , as

s hown in Table 9, anticipates using available effects data from the open literature.

Table 9

. Avai lable Ecological Effects Endpoints f or TAED

Receptor

Group Test
Material Risk
Scenario Toxicity Endpoint Reference

Freshwater fish TGAI Acute LC 50 >140 mg ai/L 45274308Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 21 of 48 Chronic Not required NA

Freshwater invertebrates TGAI Acute EC 50 >1000 mg ai/L 45712901

Chronic Not required NA

Estuarine/marine fish TGAI Acute Not required NA

Chronic Not required NA

Estuarine/marine

invertebrates TGAI Acute Not required NA

Chronic Not required NA

Sediment

- dwelling
Invertebrates TGAI Acute and Chronic Not required NA

Aquatic plants

- green algae TGAI EC 50 NOAEC Data gap NA

Birds TGAI Acute LD50 >2000 mg ai/kg 45274309

Beneficial insects TGAI Acute Not required NA



## 4.4 Exposure Analysis Plan

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates
Quantitative exposure estimates are not anticipated as being needed. If a risk assessment is conducted, a vailable OPP models that estimate exposures from discharges from wastewater treatment plant s will be used to determine EECs in the aquatic environment.



## 4.5 Effects Analysis Plan

Besides the ecotoxicity data submitted by registrants, relevant data from the ope n literature also will be used to evaluate potential direct and indirect effects . Information on how the Agency obtains and uses the open literature is presented on the Agency’s website ( http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species

_re registration_workgroup/esa_evaluation_open_literature.htm )



## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studie s include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, inclu ding effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests andDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 22 of 48 chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of registration decision for TAED , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the e xisting hazard database. However, as required by FFDCA section 408(p), TAED 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 estro gen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

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

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert in gredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 24 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known o r 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. 25



## 6 Optional Label Changes

Th e Agency invites comment on any label amendments that could be considered to eliminate the anticipated need for EPA to require certain data, reduce the possibility that EPA’s planned risk assessments overestimate risk due to reliance on conservative assump tions, and/or improve label clarity.



## 7 Guidance for Commenters

7.1 Preliminary Work Plan

The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work plan for the TAED registration review case.

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.

25 http://www.epa.gov/endo/Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 23 of 48 

### 7.1.1 Trade Irritants
Through the registration review process, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible

. Stakeholders are asked to comment on any trade irritant iss ues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature of the

concern.



### 7.1.2 Water Quality
The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Managemen t Process 26 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.



### 7.1.3 Environmental Justice
EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race , color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to TAED compared to the general population. Please comment if you are aware of any sub

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



### 7.1.4 Structure Activity Relationships
EPA must rely upon information of appropriate quality and reliability for each decision made by the Agency. In the OPP, the evaluation process for a pesticide chemica l traditionally begins with the applicant’s submission of a set of studies conducted with the specific pesticide chemical of interest. The use of the results of such testing (measured data) is a logical, scientifically rigorous process that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

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

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

- making process. In the SAR process, a chemical's molecular structure is compared to that of other chemicals for which data are available. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties. Thus, the chemical’s physica l, chemical, and biological properties are a function of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To

26 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htmDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 24 of 48 develop a QSAR, a selected set of measured data on a single physical, chemical, or biological property is used to derive a model (an equation) to predict the value of that property.

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

- by

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

- of

- the

evidence evaluation.

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

- lined, i.e., a screening

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

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the
TAED Case, then the Agency invites submission of this information. The submitter would be expected to supply a rationale describing the utility of the informat ion and provide documentation on the scientific validity of the information. The determination that the predicted data fulfills the data requirement would be at the sole discretion of the Agency. Pre

- submission consultation with the Agency is encouraged.



### 7.1.5 Additional Information

Stakeholders are also specifically asked to provide available information and data that will assist the Agency in refining its risk assessments, including human health risk assessments or species

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

1. State or local use restrictions

. 2. Ecological incidents (non

- tar get plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency

. 3. Monitoring data

. 4. Human health toxicology or metabolism studies that could be used to evaluate the need for the anticipated to be required toxicity studies ( Prenatal Developmental Toxicity, Reproduction and Fertility Effects and Immunotoxicity).



## 8 Next Steps

After the 60

- day comment period closes in Ma y 2014 , the Agency will review and respond to any comments received in a timely manner, and then issue a Final Work Plan for the TAED case.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 25 of 48 

## 9 References

HERA, 2002. Human and Environmental Risk Assessment on Ingredients of European household cleaning products: Tetraacetylenediamine (TAED), Caffaro , Clariant, Henkel, Unilever, P&G and Warwick, December 2002.

U.S. Environmental Protection Agency (EPA). 2002. ECOTOX User Guide: ECOTOXicology Database System. Version 3.0. Available: http://www.epa.gov/ecotox/ U.S. Environmental Protection Agency. High Production Volume Information System (HPVIS). http://www.epa.gov/ hpvis/Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 26 of 48 

# Appendix A T oxicology Profile

1.0 Acute Toxicity

The database for acute toxicity for TAED is considered complete. It consists of seven studies that have been submitted to EPA and these studies are listed in Table 1

. These studies indicate that T AED is of low acute toxicity (i.e. Toxicity Categories III and IV) by all routes of exposure and that TAED is not a dermal sensitizer.

Table 1

– TAED Acute Toxicity Studies

Guideline No. Data Requirement /Species MRID Results [Comments] Toxicity Category

870.1100 Acute Oral/Rat 452997

- 02 LD 50 = 7940 mg/kg/day [Acceptable/Non

- Guideline] IV

870.1200 Acute Dermal/Rabbit 457129

- 02 LD 50 >2000 mg/kg [Acceptable/Guideline] III

870.1300 Acute Inhalation/Rat 462048

- 01 >2.08 mg/L [Acceptable/Guideline] IV

870.2500 Dermal Irritation/ Rabbit 457129

- 03 Not a skin irritant [Acceptable/Guideline] IV

870.2500 Dermal Irritation/ Rabbit 452997

- 02 Not a skin irritant [Acceptable/Non

- Guideline] IV

870.2400 Primary Eye Irritat ion /

Rabbit 457129

- 03 Corrosive [Acceptable/Guideline] IV

870.2600 Dermal Sensitization/ Guinea Pig 452997

- 02 Not a dermal sensitizer [Acceptable/Non

- Guideline] N/A

2.0 Repeat Dose Toxicity

The database for repeat dose toxicity includes three studies that have been submitted to EPA as well as three studies that are included in the HERA, 2002 document for TAED. These studies are listed in Table 2

.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 27 of 48 Table 2

– TAED Repeat Dose Toxicity Studies

S tudy Type/ Test Substance Source / Doses Results

Studies Submitted to EPA

90 Day Oral Toxicity Study in Rat s MRID 45299703 0, 25, 500, 1000 mg/kg/day NOAEL = 25 mg/kg/day (F) LOAEL = 500 mg/kg/day, based on centrilobular cytomegaly (hypertrophy) in the liver, increased liver weight, and clinical chemistry changes.

90 Day Dermal Toxicity Study in Rat s MRID 45274305 0, 20, 200, 2000 mg/kg/day N OAEL = 200 mg/kg/day LOAEL = 2000 mg/kg/day based on centrilobular hypertrophy of the liver Oral (Gavage) Developmental
T oxicity Study in Rat s MRID 45299704 0, 40, 200, 1000 mg/kg/day M aternal NOAEL = 40 mg/kg/day
Maternal LOAEL = 200 mg/kg/day based on reduced body weight gain and food consumption

Developmental NOAEL = 200 mg/kg/day
Developmental LOAEL = 1000 mg/kg/day based on decreased mean fetal weights and increased incidence of skeletal variations Studies from HERA, 2002

28 Day Gavage Study in Rat s RCC,1989 0, 40

, 2 00, 1000 mg/kg/day N OAEL = 200 mg/kg/day LOAEL = 10 00 mg/kg/day, based on increased liver weight, slight hepatic centrilobular parenchymal hypertrophy

90 Day Gavage Study in Rats

. Henkel, 1987 0, 9 0, 2 5 0, 800 mg/kg/day N OAEL = 90 mg/kg/day LOAEL = 250 mg/kg/day based on increased liver and testes weights in male rats. 90 Day Whole Body Inhalation Study in
Rat s TAED, (<3.5 um)

. Unilever, 1981 12.2, 60.3, 99.7 mg/m 3 6 hours/day, 5 days/week NOAEL = 99.7 mg/m 3 (HDT)

Microscopic observation showed no treatment induced effects on the lungs.

2.1 Subchronic Toxicity

The database for subchronic toxicity is considered complete. This database includes three oral toxicity studies, one dermal toxicity study and one inhalation toxicity studyDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 28 of 48 2.1.1 Subchronic Oral Toxicity

MRID 45299703

- In a 90

- day oral toxicity study TAED was administered to 10 rats/sex/dose by gavage in 1% carboxymethylcellulose (CMC) at nominal dose levels of 0, 25, 500, or 1000 mg/kg/day.

There were no treatment

- related findings regarding mortality, clinical signs of toxicity, ophthalmology, and hematology. Significant dose

- related decreases in body weight and body weight gain were observed in treated males at all dose l evels and ≥ 500

- mg/kg/day in treated females. Food consumption was decreased in treated rats but the decreases reached statistical significance only in the 1000

- mg/kg/day males. Significant increases occurred in total protein (1000

- mg/kg/day males and fema les), albumin (1000

- mg/kg/day males), and globulin values (1000

- mg/kg/day females). Liver weights (absolute, relative to body and brain weights) were significantly increased in the 1000

- mg/kg/day males and ≥ 500

- mg/kg/day females that correlated with incid ences of grossly enlarged liver in 1000

- mg/kg/day males and incidences of centrilobular cytomegaly of the liver (1000 mg/kg/day males) in all 500

- and 1000

- mg/kg/day treated rats. Bilateral, mild degeneration of the seminiferous tubules was noted in 2/10 high

- dose males.

Based on weight loss and decrease in the rate of weight gain, microscopic lesions observed in the liver (centrilobular cytomegaly), increased liver weights, and clinical chemistry changes, the LOAEL is 500 mg/kg/day in females and 25 mg/kg /day in males. The NOAEL is 25 mg/kg/day in females, but could not be determined in males (<25 mg/kg/day).

This 90

- day oral toxicity study is Acceptable/Guideline and it satisfies the guideline requirement for a 90

- day subchronic oral toxicity study [OPPTS 870.3100 [§82

- 1]; OECD 408] in rats

.

RCC, 1989. Subacute oral toxicity was evaluated in groups of 10 rats (5 males, 5 females) receiving TAED by once daily gavage at dose levels of 0, 40, 200 and 1000 mg/kg /day for 28 days. Mortality, clinical abnormalities, ophthalmoscopic findings and toxicologically relevant changes of hematological, biochemical and urinalysis parameters were not observed throughout the study. Food consumption in male rats of the high dose gr oup and female rats of the high and mid dose group was significantly less than the controls during treatment days 1 to 8. The same occurred in female rats of the high dose group during treatment days 15 to 28. The body weights and body weight gains of the high dose female rats were significantly lower than control from day 15 until the end of the 28 day treatment period. A significant increase of absolute and relative liver weights was found in male and female rats of the 1000 mg/kg /day group. Male rats of this group showed also significantly reduced absolute and relative spleen weights. Histopathological examination revealed slight hepatic centrilobular parenchymal hypertrophy, consistent with enzyme induction, in male and female rats of the high dose group . The lower dose levels produced no pathological evidence of toxicity.

Based upon the results a NOAEL of 200 mg/kg/day was determined. The study was performed according to GLP standards and OECD guideline 407 and is therefore reliable without restrictions (data quality score 1). This study is also acceptable under the analogous EPA guideline (OCSPP 870.3050)

.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 29 of 48 Henkel, 1987

. G roups of 10 male and 10 female rats receiv ed TAED by gavage at daily dose s of 0, 90, 250 and 800 mg/kg /day for 90 days. A recovery control and high dose group consisting of 5 male and 5 female rats was terminated 28 days after the 90 day treatment period.

Mortality did not occur. Salivation observed in the animals of the high dose group was the only clinical finding. Water consumption was increased in males of the 250 and 800 mg/kg /day group and in all female test groups, whereas food consumption was not affected. Total body weight gain was decreased in male and female rats of all high dose groups.

Slightly d ecreased haematocrit values in all male test groups and an increase in leukocytes in females of the high dose were observed. Changes in biochemical parameters considered to be compound

- related comprised increased protein values in male and female rats of t he high dose group and increased cholesterol values in female animals treated with 800 mg/kg /day . Eye examination revealed no compound related findings. At the dose level of 250 mg/kg /day relative liver and testes weights were significantly increased in ma le rats. At 800 mg/kg /day absolute and relative liver weights of both sexes and relative adrenal and testes weights in male rats were statistically significantly increased. No compound related macroscopically visible findings were present at necropsy. Hist opathological examination revealed centrilobular hypertrophy of hepatocytes in all high dose animals. This effect reversed completely within the 28 day recovery period. In the animals of the low and mid dose group centrilobular hypertrophy was borderline i n some rats and not considered a clear substance related effect, since this finding was also present in some control animals of the recovery group.

Definitive treatment

- related adverse effects occurred at the dose level of 800 mg/kg/d ay

. Changes in organ weights were present at 250 mg/kg /day . No adverse effects were observed at 90 mg/kg/day. Hence, a “no

- adverse

- effect

- level” of 90 mg/kg/day can be deduced. The study was performed according to OECD guideline 408 and GLP and is therefore reliable without

r estrictions (data quality score 1). This study is also acceptable under the analogous EPA guideline (OCSPP 870.3100).

2. 2.2 Subchronic Inhalation Toxicity

Unilever, 1981

. T hree groups of 12 male rats were exposed in inhalation chambers to mean

concentr ations of TAED dust (< 3.5 μm) of 12.2, 60.3 and 99.7 mg/m 3 for 6 hours a day, 5 days a week, for 13 weeks. A control group of 12 male rats was sham

- exposed. Male rats were used, as they were more sensitive than females in the acute inhalation study. Follo wing exposure, 6 rats from each group were killed and examined by whole body necropsy. The remaining rats were maintained without further treatment for 13 weeks to investigate the reversibility of any

treatment

- related effects.

Mortality did not occur. Th ere were statistically significant increases in absolute and relative liver and kidney weights. All organ weights returned to normal values following the recovery period, apart from a small increase in liver weight at the high dose. There was a statistical ly significant reduction in hemoglobin and an increase in platelet numbers in the rats exposed to the high level of TAED, and an increase in the number of monocytes in the high and mid levelDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 30 of 48 exposure groups. These values were within normal limits following the 13

- week recovery period. Levels of glucose and aspartate transaminase activity were reduced in all TAED exposure groups. Increased Ca2+ , serum total protein and albumin and reduced alanine transaminase activity were found in the high and mid

- exposure groups, and increases in total cholesterol and pseudo

- cholinesterase activity and reduced alkaline phosphatase activity in the high level group. The values had returned to normal after the recovery period. At post

- mortem, one rat exposed to the high level of TAED had a slight enlargement of the liver, otherwise no abnormal features were observed in any of the rats.

Microscopic examination showed no treatment

- induced effects in the lungs. There was a systemic response as evidenced by significant increases in kidney weights in the high and mid exposure groups, and in liver weights in all exposure groups. This was reflected in changes in hepatic and renal morphology. The morphological change seen in the liver was hypertrophy of centrilobular hepatocytes. This was considered to be due to induction of hepatic microsomal drug metabolizing enzymes, based on further ultrastructural studies that demonstrated proliferation of smooth endoplasmatic reticulum in these hepatocytes. The morphological changes found in the kidneys were eosinophilic droplets in the tubular epithelial cells, usually referred to as hyaline droplets composed principally of the normal male rat urinary protein α2μ

- globulin. The fact that in another Unilever study female rats fed TAED did not devel op this pathology, but males did, confirms this to be the case (Carthew, 2001). The kidney findings are therefore specific to the male rat and not relevant to humans. Examination of recovery rats showed that these effects reversed completely during a 13

- we ek recovery period.

The NOAEL for systemic effects cannot be derived from this study as the whole body of the animals was exposed to TAED dust and the oral ingestion of unquantifiable amounts of substance would have occurred due to grooming. Under the con ditions of this study, repeated exposure by inhalation to TAED dust at doses up to 99.7 mg/m 3 did not cause any adverse effects in the rat lung, respiratory tract or nasal mucosa.

The study was conducted according to GLP standards and while the report doe s not state whether it was conducted according to a recognized guideline, the study does meet the requirements of OECD Test Guideline No. 413. However, small group sizes were used. The study is therefore valid with restrictions (data quality score 2, assi gned by Unilever (Moran, 2002). Because of the small group sizes, this study is also rated as supplemental under the analogous EPA guideline (OCSPP 870.3465).

2.3.3 Subchronic Dermal Toxicity

MRID 452743

- 05 TAED as a paste in 1% CMC was applied daily to the shaved skin of ten rats/sex/dose at dose s of 0 (vehicle control), 20, 200, or 2000 mg/kg/day, for 6 hours/day during a 90

- day period.

Exposure to the test article did not result in increased mortality, clinical signs, or significant changes in body wei ght or body weight gain, food consumption, hematology, clinical chemistry, ophthalmology, organ weights, or gross necropsy findings. Exposure at the highest dose resulted in an increase in centrilobular hypertrophy of the liver, which was not observed at lower doses.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 31 of 48 The LOAEL for systemic toxicity is >2000 mg/kg/day. The NOAEL for systemic toxicity is 200 mg/kg/day.

This study is Acceptable/Guideline and satisfies the guideline requirement for a 90

- day dermal toxicity study (OPPTS 870.3250 [§82

- 3]; OECD 411) in the rat.

2.3 Developmental Toxicity

This database for developmental toxicity consists of one study (MRID 45299704) and this study was done on the rat. The database for developmental toxicity is considered incomplete because only one species has b een tested.

MRID 45299704 . TAED was administered to 25 mated female rats/dose by gavage at dose levels of 0, 40, 200, or 1000 mg/kg/day from days 6 through 15 of gestation.

Maternal toxicity was observed at 1000 and 200 mg/kg/day. Treatment

- related ef fects at 1000 mg/kg/day included decreased body weight, body weight gain, corrected body weight, corrected body weight gain, and food consumption. Treatment

- related effects at 200 mg/kg/day were similar to those observed at the high dose and included decr eased body weight gain, corrected body weight gain, and food consumption. The maternal LOAEL is 200 mg/kg/day, based on a reduction in body weight gain, corrected body weight gain, and food consumption. The maternal NOAEL is 40 mg/kg/day.

Fetal toxicity was observed at 1000 mg/kg/day, with treatment

- related effects including decreased mean fetal weights (male, female, and combined) and an increased incidence of skeletal variations. There were no treatment

- related effects observed at 200 or 40 mg/kg/day.

The developmental LOAEL is 1000 mg/kg/day , based on decreased mean fetal weights and increased incidence of skeletal variations. The developmental NOAEL is 200 mg/kg/day.

This study is classified as Acceptable/Guideline and satisfies the guideline requ irements for a developmental toxicity study (OPPTS 870.3700 [§83

- 3a]; OECD 414) in rats.

2.4 Reproductive Toxicity

There are no reproductive toxicity studies available for TAED ; however, a significant increase in testes weights w as observed in one of th e two 90 day oral toxicity studies ( Henkel, 1987). Because of this finding and because a reproductive effect toxicity study is required by 40 CFR
Part 158W, a reproductive toxicity study is anticipated to be needed for TAED.

2. 5 Neurotoxicity

There are no neurotoxicity studies available for TAED. The study is conditionally required per 40 CFR Part 158W if the neurotoxicity screen in the 90 day oral rodent study or other dataDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 32 of 48 indicates neurotoxicity. Neurotoxicity has not been observed in the TAED toxicity studies and therefore the neurotoxicity study is not anticipated to be required for TAED.

2.6 Mutagenicity

Three mutagenicity studies have been submitted for TAED and the results are summarized in Table 3

. TAED was negative for mutagenic effects in all three studies.

Table 3

– TAED Mutagenicity Studies

Study Type MRID Number Results

Ames assay 45274306 No evidence of mutagenicity in strains TA98, TA100, TA1535, TA1537, and TA1538 (with or without S9 )

I n vivo micronucleus

assay 45547202 No significant increase in frequency of micron nucleated PCEs at any dose level tested

H uman lymphocyte chromosome aberrations 4 5547201 No repeatable significant increases in either frequency of structural aberrations or frequency of polyploidy cells at any dose level tested.

2.7 Chronic Toxicity and Carcinogeneticity

There are no chronic toxicity or carcinogeneticity studies available for TAED ; however, these studies are not needed for TAED because the use pattern does not involve food exposure or long term occupational and residential exposure

.

2.8 Immunotoxicity

There are no Immunotoxicity studies for TAED

. Accord ing to subpart 40 CFR Part 158 W and based on the existing toxicity database and use pattern, this study is anticipated to be required for TAED registration review.

3.0 Biotransformation

A biotransformation study for TAED (Unilever, 1978a) is included in the HERA, 2002 document. The fates of tetra acetyl [ 14 C]ethylene diamine (TA[ 14 C]ED) and [1

- 14 C]tetra acetyl ethylene diamine ([ 14 C]TAED) were followed in groups of 3 male and 3 female Wistar rats after oral intubation with 0.5 ml dietary slurry containing 5 mg TA[ 14 C]ED or 4.6 mg [ 14 C]TAED (Unilever, 1978a). The nature of the radio

- labelled compounds in urine and feces was studied and 14 C levels were monitored in tissues, carcass remains, urine and feces. A further group of rats was intubated with [ 14 C ]TAED and killed at 1, 2, 4, 7 and 24 hours to monitor the rate of absorption from the intestine and uptake by the liver, adrenal and kidney tissues. Monitored 14 C levels showed no gender differences in the absorption, metabolism and excretion of TA[ 14 C]ED and [ 14 C]. At one hour post

- dosing, more than 50% of the administered 14 C had been absorbedDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 33 of 48 from the intestine. Tissue levels of 14 C were at their highest at 2 hours post

- dosing. Subsequently, levels fell rapidly except in the adrenal gland where 14 C lev els rose during the 7 hours post

- dosing. More than 90% of the urinary 14 C was excreted within 24 hours of dosing. Chromatographic analysis showed only traces of TAED in the urine. Most of the 14 C was excreted as triacetyl ethylene diamine (TriAED) and diac etyl ethylene diamine (DAED). Mono acetyl ethylene diamine (MAED) and ethylene diamine were not found.

The results show that TAED was rapidly absorbed from the rat intestine and was largely metabolized and excreted in the urine within 24 hours. Difference s in the levels of 14 C recovered as expired CO 2 reflect the different metabolic fates of the acetyl and ethylene diamine moieties.

The 14 C compounds identified in the urine, TirAED and DAED, indicate that deacetylation was the mai n metabolic route for TAED in the rat.

4.0 Dermal Penetration

A dermal penetration study for TAED (Unilever, 1978b) is included in the HERA, 2002 document. Skin penetration studies using TA[ 14 C]ED in detergent solutions and in chloroform were conducted in rats

. One group of Wistar rats was treated with 0.2 ml of a 1% w/v detergent A base containing 400 μg TA[ 14 C]ED applied over 10 cm 2 of clipped dorsal skin. A second group was treated with 200 μl of a solution containing 6% pow der detergent B base, 1% perborate and 0.5% TA[ 14 C]ED (1348 μg TA[ 14 C]ED) and a third group was treated with 50 μl chloroform containing 1124±40μg TA[ 14 C]ED. The amounts of TA[ 14 C]ED penetrating the skin measured. Of the TA[ 14 C]ED which penetrated the ski n, most was recovered in the urine while less than 3% was recovered in the feces. The results indicate that TAED can penetrate rat skin depending on contact time, with increased contact time leading to increased skin penetration.

5.0

. Data Gaps :

According to subpart 40 CFR Part 158 W and based on the existing toxicity database and use pattern, the following data requirements apply to TAED.

1) Immunotoxicity

2) Reproduction toxicity

3) Developmental toxicity (non

- rodent)Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 34 of 48 6 .0 Open Literature R eferences for Appendix A.

Henkel, 1987. Henkel KGaA

– Institut für Toxikologie. Tetra

- acetyl

- ethylen

- diamin

– 90

- Tage

- Test mit wiederholter oraler Verabreichung an Ratten. Unpublished data. Archive No. 860114. (Cited in HERA, 2002)

HERA, 2002. Human and Environmental Risk Assessment on Ingredients of European household cleaning products: Tetraacetylenediamine (TAED), Caffaro , Clariant, Henkel, Unilever, P&G and Warwick, December 2002.

RCC,1989. RCC AG on behalf of Hoechst AG

– Pharma Forschung Toxikologie and Pathologiue (1989) . Subacute 28

- day oral toxicity (gavage) study with TAED in the Rat. Unpublished data. Project No. 233820 (Cited in HERA, 2002)

Unilever, 1978a. Unilever’s Toxicology Lab

. Tetra acetyl ethylene diamine (TAED): Oral absor ption, metabolism and excretion study in rats

– summary of study no. AM77.01 (report no. P CE 78 1147). In: SEAC Toxicology Group

- Unilever Research Colworth (2001). Tetra acetyl ethylene diamine (TAED): Toxicity and ADME summary data. Unpublished data. D ocument reference D01

- 023. (Cited in HERA, 2002)

Unilever, 1978b. Unilever’s Toxicology Lab

. Tetra acetyl ethylene diamine (TAED): Skin penetration study in rats

– summary of study no. AM77.01 (report no. PCW 78 1147). In: SEAC Toxicology Group

- Unileve r Research Colworth (2001). Tetra acetyl ethylene diamine (TAED): Toxicity and ADME summary data. Unpublished data. Document reference D01

- 023. (Cited in HERA, 2002)

Unilever, 1981. Unilever’s Toxicology Lab. Tetra acetyl ethylene diamine (TAED): 13

- week inhalation toxicity study in rats

– summary of study no. R1234 (IT80.004). In: SEAC Toxicology Group

- Unilever Research Colworth (2001). Tetra acetyl ethylene diamine (TAED): Toxicity and ADME summary data. Unpublished data. Document reference D01

- 023. (C ited in HERA, 2002)Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 35 of 48 

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of TAED and its Degradates TriAED and DAED and Perhydrolysis Products Peroxyacetic Acid and Hydrogen Peroxide

The Agency will conduct an environmental fate assessment for TAED based on the current uses in industrial and institutional laundry facilities and hard, non

- porous surfaces in healthcare facilities, hospitals, medical, and dental offices. It serves as a b leach activator and reacts in aqueous solutions in the presence of an oxygen activator to form the DAED degradate, hydrogen peroxide and peracetic acid using the perhydrolysis reaction 27

. Both peroxyacetic acid and hydrogen peroxide are highly

- reactive and degrade rapidly.

Guideline environmental fate data that address metabolism or transport of TAED in the terrestrial or aquatic environment have not been submitted to the Agency for TAED or it ’ s degradates. Although no data have been submitted, TAED and the degradates

, TriAED (transient degradate) and DAED (terminal non

- volatile degradate)

, a re expected to partition to water in the presence of sludge based on a log Kow of

- 0.06. 28 Several studies are present in the literature and in the HERA document. 29 The studies listed in the HERA document have not been formally

- reviewed by the Agency, but they indicate that TAED is readily biodegradable 30 and highly removed in the activated sludge of a WWTP based on a 97 percent removal rate in a porous pot test. 31 Th e appropriate studies in the HERA document will be formally

- reviewed by the Agency before a final risk assessment. The Agency also has not received data on aerobic aquatic metabolism of parent TAED or the degradate DAED, which can reach surface water if

t hey pas through a WWTP.

Parent TAED is miscible in water (20 g/L) 32 and its sequential degradates TriAED and DAED are expected to have similar water solubility based on structural similarity. TAED (TGAI) slowly degraded by abiotic hydrolysis at pH 7 and 15 o C with a half

- life of 40 days and the DAED degradate was shown to be stable and not degrade. 33 However, in a washing machine study using a formulated product which includes oxygen, TAED appears to degrade rapidly to form the degradate DAED at 30, 40, and 60 o C 34 which represents cold, warm, and hot water temperatures, respectively. 35 The washing machine study, which is more environmentally

-

27 Reaction in water to release peroxyacetic acid and hydrogen peroxide

28 MRID 45299701

29 Human & Environ mental Risk Assessment, http://www.heraproject.com/files/2

- F

- 04

- HERA%20TAED%20full%20web%20wd.pdf

30 OECD 301E data, IUCLID 2000, Proctor & Gamble Internal Data 1976 an d 1978

31 Clariant, 2002

32 MRID 45299701

33 MRID 46335801

34 MRID 46335802, study not reviewed

35 http://housekeeping.about.com/od/laundry/a/laundry_h20temp.htmDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 36 of 48 relevant than the abiotic hydrolysis study, has not been formally

- reviewed. It will be reviewed prior to conducting the risk assessment. The only detectable residue from the water in the washing machine was th e DAED degradate.

Water and Sediment

Hydrolysis

The only submitted guideline environmental fate study on TAED is hydrolysis (MRID 46335801) 36 which indicates relative stability of parent TAED with a half

- life of 40 days at pH 7 and 15 o C. The major hydrolytic degradate TriAED (once

- deacetylated TAED) reached 40 % of parent compound by 60 days and had a half

- life of 120 days. The terminal degradate DAED (twice

- deacetylated TAED) reached 50 % of parent compound by 180 days and did not degr ade in the study.

The Agency also had access to a washwater study that used TAED (MRID 46335802) 37 . At 30

o C (86 o F), 40 o C (104 o F), and 60 o C (140 o F), parent TAED dissipated by the end of the wash cycle and the only residue remaining was the degradat e DAED. These temperatures approximate the cold (60

- 80 o F), warm (90

- 110 o F), and hot ( > 130 o F) water temperatures for a
washer. 38 The lack of degradation of the DAED degradate was consistent with the results of the hydrolysis study, and DAED is the residue to which the microorganisms in a WWTP would be exposed.

The abiotic hydrolysis study and the washing machine study show appare ntly contradictory results because the tested materials were different. However, the abiotic hydrolysis study used parent TAED without an oxygen activator and the washing machine study used a formulated product with an oxygen activator which promotes the perhydrolysis of parent TAED to form DAED and peroxyacetic acid.

Aqu eous Photoly s is

The registrant has not submitted any photodegradation in water (835.2240) or photodegradation on soil ( OCSPP 835.2410) data for TAED or its degradates. However, based on t he limited sorption of UV light 39 , these data are not required because the study would not provide any meaningful results.

36 MRID 46335801, find review date

37 MRID 46335802 not formally

- reviewed

38 http://housekeeping.about.com/od/laundry/a/laundry_h20temp.htm

39 MRID 45299701Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 37 of 48 Octanol

- Water Partition Coefficient

The octanol water coefficient (Log Kow or Log P) is

- 0.06 40 , which indicates limited potential
for bioconcentration in fish (OCSPP 850.1730) or for sorption to activated sludge (OCSPP 835.1110) or to soil and sediment (OCSPP 835.1230).

Aerobic Aquatic Metabolism

The registrant has not submitted any guideline stu dies for aerobic aquatic metabolism (OCSPP 835.4300) and the Agency anticipates requiring data for this test guideline. If TAED or its degradate DAED reach surface water, they will likely be associated with the water column in the presence of sediment.

A n a erobic Aquatic Metabolism

The registrant has not submitted any guideline studies for anaerobic aquatic metabolism (OCSPP 835.4400) but the Agency does not anticipate requiring data for this test guideline for TAED and DAED because of the lack of sorption would indicate little/no TAED in the anaerobic (sediment) phase of the aquatic system

.
Soil Leaching/Adsorption/Desorption Batch Equilibrium

The registrant has not submitted any guideline studies on sorption to soil and sediment (OCSPP 835.1230). However, there are two unreviewed studies ( AISE, 1992, Shell, 2000 ) for TAED and AISE, 1992 for DAED . These studies indicate that sorption to soil i s limited for both compounds with Koc values of 15

- 80 L/kg for TAED and 25 L/kg for DAED. The apparent lack of sorption to soil is consistent with the high water solubility of 20 g/L and the low log Kow of

- 0.06. Studies will be reviewed prior to conduct of risk assessment but do not impact data requirements at this time.

Aerobic Soil Metabolism

No data on aerobic soil metabolism (OCSPP 835.4100) have been submitted, and none are anticipated to be required. Based on the current uses, TAED is not likely t o be reach soil because of limited sorption to activated sludge or to be sorbed to soil based on the AISE (1992)

, and Shell (2000) studies cited above.

A n a erobic Soil Metabolism

No data on an aerobic soil metabolism (OCSPP 835.4200) have been submitted, and none are anticipated to be required. Based on the current uses, TAED is not likely to be reach soil because of limited sorption to activated sludge or to be sorbed to soil based on the AISE (1992) and Shell (2000) studies cited above.

40 MRID 45299701Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 38 of 48 Fate and Transport in WWTP

Activated Sludge Sorption Isotherm

Data on sorption to activated sludge are not anticipated to be required because the log Kow (Log P) is

- 0.06 (<3 and indicates no sorption.

Activated Sludge Biodegradation

TAED and its degradates TriAED and DAED a re miscible in water 41 and are expected to partition to water in the presence of sludge based on a log Kow of

- 0.06. 42 The Agency has not received any submitted guideline studies for the biodegradation of TAED, but several studies are present in the literat ure and in the HERA document. 43 The studies listed in the HERA document have not been formally reviewed by the Agency, but they indicate that TAED is readily biodegradable 44 and highly removed in the activated sludge of a WWTP based on a 97 % removal rate in a porous pot test. 45 The Agency has not formally reviewed these studies but will review them before conducting the final risk assessment.

Hydrogen Peroxide

Based on information from the open literature and the peroxy compounds, RED and registration review, u nder abiotic conditions, hydrogen peroxide does not appear to be hydrolytically or photolytically stable. The half

- life in water under abiotic conditions has not been determined absolutely, but it varies with concentration. In seawater, the DT 20 of hydrogen peroxide was 25

- 35 minutes. The half

- life of hydrogen peroxide (90% purity) was 8.3 days in the presence of sunlight in the UV range. Hydrogen peroxide is not expected to pose any concerns for surface water runoff.

Under aerobic aquatic me tabolism conditions, hydrogen peroxide degrades with half

- lives of 1.1

- 5.3 hours in non

- sterile conditions, and ca . 80 hours in sterile conditions. Under anaerobic soil metabolism conditions, hydrogen peroxide degrades with a half

- life of ca . 4 hours in s amples of nine petroleum

- contaminated surface soils from five different states. The texture and pH of the soil, as well as the experimental temperature, did not affect the degradation process; however, the organic carbon content of the soil did affect the degradation. Under aerobic soil metabolism conditions, hydrogen peroxide degrades with a half

- life of ca . 1.4 hours in diluted test solutions. This half

- life value was extrapolated to ca . 7 hours for concentrated test solutions.

T here are no data on the mobility of hydrogen peroxide in regards to either adsorption/desorption (to determine K d ) with various soils or soil column leaching. However, it is assumed that, since hydrogen peroxide has physical properties that are similar to water, hydrogen peroxi de will not bind to soils.

41 MRID 45299701

42 MRID 45299701

43 Human & Environmental Risk Assessment, http://www.heraproject.com/files/2

- F

- 04

- HERA%20TAED%20full%20web%20wd.pdf

44 OECD 301E data, IUCLID 2000, Proctor & Gamble Internal Data 1976 and 1978

45 Clariant, 2002Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 39 of 48 The Agency does not have data on hydrogen peroxide bioaccumulation in aquatic organisms. However, h ydrogen peroxide is not expected to bioaccumulate due to its low octanol

- water partition coefficients (0.40).

The average degradation half

- life for hydrogen peroxide in the atmosphere is 24 hours.

P eroxyacetic Acid

Peroxyacetic acid is expected to easily degraded in air, water and soil and does not persist or accumulate in the environment. The half

- lives/DT 50 s for peroxyacetic acid are 48 hours at pH 4 and 7, and 3.6 hours at pH 9. In water containing 0.01 mol/L, the half

- lives were 107, 109, and 112 hours for pH values of 4, 7,and 9, respectively. For solutions containing 0.001 mol/L, the half

- lives were 3.5, 3.5, and 0.3 hours, respectively. In seawater, the DT 50 of peroxyacetic acid

was 7

- 20 minutes. Only a minor portion (<1%) of peroxyacetic acid, which is released into the environment, will remain in the atmosphere, where it is rapidly degraded (half

- life of 22 minutes ) . Peroxyacetic acid will not partition into sediment, suspended matter

, or biota. In the OECD Closed Bottle Test with adapted bacteria, peroxyacetic acid (initial concentration of 2

- 5 mg/L) was highly biodegradable (>79%).

The hydrol ysis products of peroxyacetic acid (acetic acid and hydrogen peroxide) are readily biodegradable. The biodegradation/DT 50 of peroxyacetic acid is rapid (not defined). The ready biodegradation of peroxyacetic acid is >70%

. In soil, diluted peroxyacetic a cid is rapidly and easily degraded via hydrolysis and instantaneously degraded via transition metal decomposition. At low concentrations, biodegradation could contribute to the degradation in soils. After ca . 20 minutes, 99.2% of the peroxyacetic acid (1 .1% solution) had degraded in dried soil (not specified) following extraction with demineralized water.

The soil column leaching of peroxyacetic acid was studied in an unspecified soil. At 5 minutes post

- treatment, 21.5% of the peroxyacetic acid was reco vered, along with 42% of hydrogen peroxide, at a soil depth of 25 mm. The recovery of peroxyacetic acid decreased to 3.2% at 50 mm, 0.3% at 100 mm, and <0.2% at 150 mm. At 150 mm, 10% of hydrogen peroxide was present. At 10 minutes post

- treatment, the c olumn washing yielded only 8.7% recovered peroxyacetic acid at the 25

- mm depth. Peroxyacetic acid is not expected to bioaccumulate due to its low octanol

- water partition coefficients (0.30). Peroxyacetic acid and its transformation products, hydrogen per oxide and acetic acid, are of low molecular weight, high water solubility, low fat solubility, and have no tendency to bioaccumulate.

No photodegradation in water, photodegradation in air, anaerobic soil metabolism or accumulation studies in aquatic non

- t arget organisms information w ere found for peroxyacetic acid.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 40 of 48 Table 1. Chemical, Physical, and Environmental Fate Properties of TAED and its degradates TriAED and DAED

TAED TriAED DAED

Guideline Guidelin

e (OCSPP number unless specified) Unit Source/Comme nt (MRID Number)

CAS No. None None 10543

- 57

- 4 None None None

Molecular formula None None C 10 H 16 N 2 O 4 C 8 H 14 N 2 O 3 C 7 H 14 N 2 O 2 None

Smiles code None None O=C(N(C(=O)C)CCN(C(=O)C)C(= O)C)C O=C(NCCN(C(=O)C)C(=O)C)C O=C(NCCN(CC(=O)C))C None

Molecular weight None g/mol 228.25 186.21 158.20 None

Melting point 830.7200 o C 147 + 1 No data, but expected to be similar based on structural similarity No data, but expected to be similar based on structural similarity 45299701

Boiling point 830.7220 o C Not applicable because it is a solid at room temperature No data, but expected to be similar based on structural similarity No data, but expected to be similar based on structural similarity 45299701

Water solubility 830.7840 g /l 2 (20 o C)

Miscible in water No data, but expected to be similar based on structural similarity No data, but expected to be similar based on structural similarity 45299701

Vapor Pressure (mm Hg) 830.7950 mm Hg No data No data No data Not applicable

Henry’s Law None atm

m 3

mol - 1 Not expected to be volatile from water into air based on miscibility in

water No data, but expected to be similar based on structural similarity No data, but expected to be similar based on structural similarity Not applicableDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 41 of 48 TAED TriAED DAED

Guideline Guidelin

e (OCSPP number unless specified) Unit Source/Comme nt (MRID Number)

Log P (log Kow) 830.7550 Unitl

ess - 0.06 No data, but expected to be similar based on structural similarity No data, but expected to be similar based on structural similarity 45299701

Hydrolysis 835.2120 Days 40 120 Stable 45299701

pH 7, 15 o C

Perhydrolysis in Washing
Process None Min 3 <5 Stable Gilbert, 1992, Buecking, 1990 46

23 o C, pH 10.1

Photodegradati on in water 835.2240 Days Not expected to photodegrade based on limited UV light sorption from 290

- 800 nm No data, but expected to be similar based on structural similarity No data, but expected to be similar based on structural similarity 45299701

Leaching

adsorption

desorption to soil 835.1230 ml/g Koc values 15

- 80 L/kg No data Koc value of 25 L/kg AISE, 1992, Shell, 2000 (for TAED)

AISE, 1992 for
DAED 47

Aerobic aquatic metabolism 835.4300 Days No data No data No data Not applicable

46 Gilbert (1992) and Buecking (1990) have not been reviewed by the Agency

47 Koc values from AISE (1992) and Shell (2000) have not been validated through Agency ReviewDocket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 42 of 48 TAED TriAED DAED

Guideline Guidelin

e (OCSPP number unless specified) Unit Source/Comme nt (MRID Number)

Anaerobic aquatic metabolism 835.4400 Days No data No data No data Not applicable

Activated sludge sorption 835.1110 %

, L/kg No data No data No data Not applicable

Ready biodegradabilit

y 835.3110

OECD 301D % 52

- 56 % degradation in 28 days No data 60 % degradation in 28 days Henkel, 1972 48

Activated sludge respiration inhibition 850.3300 m g/l No data No data No data Not applicable

Bioconcentrati on in fish 49 850.1730 Unitl

ess No data No data No data Not applicable

Bioconcentration in aquatic organisms is not likely because of the low log Kow of

- 0.06 (<3)

48 Henkel (1972) has not been formally reviewed

49 BCF predictions should increase as the wat er solubility decreases and log Kow increases.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 43 of 48 References

About.com. January 15, 2014. Laundry and Water Temperature : What Temperature Should You Use for Your Laundry? http://housekeeping.about.com/od/laundry/a/laundry_h20temp.htm

AISE. October, 1992. Principles for Environmental Risk Assessment of Detergent Chemicals

in Europe; Outcome of 2 nd AISE Workshop, Limelette.

Buecking, H.W., Reinhardt, D., Lotsch, R., Ziemer, M., Pleschke, H. 1990. Environmental

behavior and testing of the biodegradation of bleach systems, Commun. Jorn. Com. Esp.
De terg. 21: 167

- 182, ISSN 0212

- 7466.

Clariant (2002), GmbH, Division FUN, Tetracetylethylenediamine

– Water Solubility

according to OECD 105, Report No H575, 2002

- 05

- 21

Gilbert PA (1992). TAED

– Tetraethylenedia m ine. In: Hutzinger O (ed). The handbook of environ m ental che m istry. Springer

- Verlag B e rlin Heidelberg, Vol u m e 3 Part F p. 319

- 328.

Henkel (19 7 2a). Henkel KGaA, TAED

– Closed Bottle Te s t , OECD 301D, Report No.

0000749 Henkel (19 7 2b). Henkel KGaA, DAED

– Closed Bottle Te s t

, OECD 301D, Report No. 149 1

HERA, 2002. Human and Environmental Risk Assessment on Ingredients of European household cleaning products: Tetraacetylenediamine (TAED), Caffaro , Clariant, Henkel, Unilever, P&G and Warwick, December 2002.

Hoechst (1983). OECD 302B, Zahn

- Wellens

- Test, Report No. W 83

- 016, 1983

Hoechst (1995a). OECD 301B, Sturm CO 2 Evolution Test, Test report No. B 812b

IUCLID (2000) CD

- ROM. Public data on high volume chemicals. Joint Research Centre, European Chemicals Bureau. Ispra, Italy

Shell. 2000. TAED: Determinati o n of soil Sorptio n Coefficient (Koc), Report No. CSC 00349

Shell (2002) TAED: Determination of soil sorption coefficient (Koc). Report CSC 00349

Unilever (1981a). TAED

– Ready biode g radability, Sturm T e st, Study Report D87038Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 44 of 48 

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Organisms

Birds

One acceptable acute

- oral (LD50) study categorize s TAED as being practically non toxic to birds. The guideline (850.2100 ) is satisfied. No additional avian toxicity data are anticipated to be needed

.

Avian Acute

- oral Toxicity

Test Species Test Material

(% ai) Toxicity Toxicity

Category EPA Study

ID

Northern bobwhite

( Colinus virginianus ) 99 LD50 >2000 mg ai/kg bw Practically nontoxic 45274309

Acceptable

Nontarget Insects

Toxicity d ata for beneficial insects (850.3020, 850.3030) are not needed to support the current use patterns of TAED.



### Toxicity to Aquatic Organisms

Freshwater Fish

One available acute toxicity study (850.1075) categorize s technical

- grade TAED as being practically nontoxic to freshwater fish. The guideline (850.1075) for acute toxicity testing is satisfied. No additional fish toxicity data are anticipated to be needed.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 45 of 48 Acute Toxicity to Freshwater Fish

Test Species Test Material

(% ai) Toxicity Endpoint

(mg ai/L) Toxicity

Category EPA Study

ID

Rainbow Trout

( Oncorhynchus mykiss) 99 96

- h LC50 >140 Practically nontoxic 45274308

Acceptable

Freshwater Invertebrates

One available acute toxicity study for the waterflea categorize s technical

- grade TAED as being practically nontoxic to freshwater invertebrates. The guideline (850.1010) for acute toxicity testing is satisfied. No additional aquatic invertebrate toxicity data are anticipated to be needed.

Acute Toxicity to Freshwater Invertebrates

Te st Species Test Material

(% ai) Toxicity Endpoint

(mg ai/L) Toxicity

Category EPA Study

ID

Waterflea

( Daphnia magna ) 99 48

- h EC50 >1000 Practically nontoxic 45712901

Acceptable

Estuarine/Marine Fish and Invertebrates

No data (850.1075, 850.1025, 850.1035) are available. Because TAED is not expected to occur in the estuarine/marine environment, data for estuarine marine organisms are not anticipated to be needed.

Aquatic Plants

No data are available. A Tier II study (850.4500) is needed for gree n algae ( Selenastrum capricornutum ) for a hazards assessment. No additional data (850.4400, 850.4500, 850.4550)

are anticipated to be needed.

Sediment toxicity

Sediment toxicity data are not anticipated to be needed based on the environmental fate propert ies of TAED.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 46 of 48 Appendix C References

45274309 Pedersen, C. (2000) Avian Acute Oral Toxicity Test With Tetraacetylethylenedia

mine in Bobwhite Quail: Lab Project Number: 168

- 001

- 03. Unpublished study prepared by Bio

- Life Associates, Ltd. 36 p. {OPPTS 850.2100}

45274308 Sousa, J. (2000) Tetra Acetyl Ethylene Diamine (TAED)

- Acute Toxicity to Rainbow
Trout (Oncorhynchus mykiss) Under Flow

- Through Conditions : Lab Project Number: 13727.6103: WI/SLI/001. Unpublished study prepared by Springborn Laboratories, Inc. 50 p. {OPPTS 850.1075}

45712901 Mattock, S. (2002) Tetraacetyl Ethylene Diamine: Acute Toxicity to Daphnia magna : Final Report: Lab Project Number : 1434/11: 1434/11

- D2149. Unpublished study prepared by Covance Laboratories, Ltd. 27 p. {OPPTS 850.1010}Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 47 of 48 

# Appendix D Product Chemistry

Tetraacetylethylenediamine product chemistry information is summarized in Table D 1 (source:
MRID No. 45299701 ).

Table D 1

– Product Chemistry of Tetraacetylethylenediamine

Guideline
No. Physical and Chemical Properties Tetraacetylethylenediamine

830.1550 Product identity and composition Refer to Table 3

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 Discussion of Formation of Impurities CBI

830.1700 Preliminary analysis CBI

830.1750 Certified limits CBI

830.1800 Enforcement analytical method GLC and F.I.D. Detection

830.1900 Submittal of samples CBI

830.6302 Color Off

- white (white/cream colored) Material

830.6303 Physical State Solid at room temperature (25 ° C)

830.6304 Odor No discernible odor
Weak acetic acid odor

830.6313 Stability to normal and elevated temperature, metals/metal ions TAED was stable under the conditions tested (room temperature and 54°C).
TAED was s table to metals and metal ions under the conditions tested (room temperatur e and 54°C). The TAED technical is expected to be stable for at least one year stored away from sunlight and at ambient temperature storage conditions. This is based on the absence of reactive or unstable groups in the product and on the result from an accelerated storage study at elevated temperature. This material was considered stable under accelerated storage stability conditions (i.e., at 54 ° C)

Stable at normal storage and handling conditions.

Conditions to Avoid: Acids; strong alkalies; strong ox idizing agents. Reacts with acids, alkalies, and strong oxidizing
agents.

TAED is stable when dry at room temperatures.

830.6314 Oxidation/Reduction The product has no oxidizing or reducing potential because there are no reactive oxidizable/reducible gr oups in the compound.Docket Number EPA

- HQ

- OPP

- 2013

- 0608 www.regulations.gov

Page 48 of 48 Guideline
No. Physical and Chemical Properties Tetraacetylethylenediamine

830.6315 Flammability Not applicable because the product contains no combustible liquids.

830.6316 Explodability Not applicable because the product is not potentially explosive.

830.6320 Corrosion Characteristic Stable with respect to metals (i.e., non

- corrosive) and did not
exhibit corrosion/degradation of LDPE and PP plastics under
the conditions tested.

830.7000 pH 5 (20 ° C, 1g/l) 5 (3% solution)

830.7050 UV/Visible Absorption TAED has a UV/VIS absorption maximum at 214 nm

830.7200 Melting point 147°C + 1°C

830.7220 Boiling point Not applicable to this product because it is a solid at room
temperature.

830.7300 Density Bulk density at 20 ° C is 430

- 520g/L

830.7100 Viscosity Not applicable because this product is a solid at room temperature and other typical environmental conditions.

830.7370 Dissociation Constant Not applicable because TAED has no dissociable groups.

830.7550 Partition coefficient ( n

- octanol/water) Log Po/w of −0.06

830.7840 Solubility in water 2 g/100 ml at 20°C

830.7860 Solubility in organic solvents Dimethyl sulfoxide: 5g/100 ml

830.7950 Vapor pressure 1.48 x 10 - 8 mm Hg 25 °C (EPI Suite v 4.1)

atm

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