Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 2 of 48 TAED Registration Review Team

Human Health & Environmental Effects James Breithaupt William Erickson Siroos Mostaghimi Timothy Dole Zoe Cavinder Steven Malish Colin Walsh

Risk Management SanYvette Williams James Parker Karen Leavy Eric Miederhoff Menyon Adams

Office of General Counsel Philip RossDocket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 3 of 48 

### Table of Contents
1 Introduction .................................................................................................................. ........... 5 1.1 Statutory and Regulatory Authority ................................................................................. 5 1.2 Updates to the Work Plan ................................................................................................. 5 1.3 Chemical Identification and Properties ............................................................................ 8 1.4 Use/Usage Description ..................................................................................................... 9 1.4.1 Registrations ............................................................................................................. 9 1.4.2 Summary of Regist ered Uses .................................................................................. 10 1.4.3 Usage Information .................................................................................................. 10 1.5 Regulatory History ......................................................................................................... 11 1.5.1 Recent Regulatory Actions ..................................................................................... 11 1.5.2 Tolerance Information ............................................................................................ 11 1.5.3 Design for the Environment .................................................................................... 11 1.6 Incidents ..................................................................................................................... .... 11 1.6.1 Human Health ......................................................................................................... 11 1.6.2 Ecological ............................................................................................................... 11 2 Anticipated Data Needs ........................................................................................................ 11 3 Human Health Risk Assessment ........................................................................................... 14 3.1 Toxicological Endpoints ................................................................................................ 14 3.2 Dietary Exposure ............................................................................................................ 1 5 3.2.1 Food ........................................................................................................................ 1 5 3.2.2 Drinking Water ....................................................................................................... 15 3.3 Occupational and Residential Exposures ....................................................................... 16 3.3.1 Occupational Exposures.......................................................................................... 16 3.3.2 Residential Exposures ............................................................................................. 16 3.4 Aggregate and Cumulative Exposure ............................................................................. 17 3.4.1 Aggregate Exposures .............................................................................................. 17 3.4.2 Cumulative Exposures ............................................................................................ 17 4 Environmental Risk Assessment........................................................................................... 17 4.1 Environmental Fate Assessment .................................................................................... 18 4.1.1 Persistence in Water and Sediment ......................................................................... 18 4.1.2 Persistence in Soil ................................................................................................... 19 4.1.3 Persistence in Air .................................................................................................... 19 4.1.4 Persistence in WWTP ............................................................................................. 19 4.1.5 Water Quality .......................................................................................................... 19 4.2 Environmental Exposure Pathways ................................................................................ 20 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 Wild life Exposure Estimates ............................................ 21 4.5 Effects Analysis Plan ..................................................................................................... 21 5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 22Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 4 of 48 6 Optional Label Changes ........................................................................................................ 23 7 Next Steps .................................................................................................................... ......... 23 8 References .................................................................................................................... ......... 23

Appendix A Toxicology Profile ................................................................................................. ... 24 Appendix B Environmental Fate ................................................................................................. . 33 Appendix C Ecotoxicicology Profile ............................................................................................ 43 Appendix D Product Chemistry .................................................................................................. .. 46 Appendix E Response to Comments............................................................................................. 48

List of Tables Table 1 – Summary of Anticipated Risk Assessments and Data Needs: TAED ............................ 7 Table 2 – Anticipated Regist ration Review Schedule .................................................................... 7 Table 3 – Chemical Identification of Tetraacetylethylenediamine (TAED) .................................. 8 Table 4 – Physical-Chemical and Envir onmental Fate Properties for TAED ................................ 9 Table 5 – Summary of TAED Registered Uses ............................................................................ 10 Table 6 – Studies Anticipated as Needed for the Registration Review of TAED and DAED ..... 13 Table 9 – Available Ecological Effects Endpoints for TAED .........................................20Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 5 of 48 

## 1 Introduction

This document is the United States Environmen tal Protection Agency’s (USEPA, EPA or “the Agency”) Final Work Plan (PWP) for registration review of the tetraacetyleneethylenediamine (TAED) case. The FWP document explains what EPA's Office of Pesticide Programs (OPP) knows about TAED, highlighting anti cipated 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 ’s review. This work plan also addresses public comments received concerning the Prelimin ary Work Plan (PWP) which was posted in the TAED registration review docket (EPA-HQ- OPP-2013-0608). Further, this document makes final the work plan for the TAED registration review process.



## 1.1 Statutory and Regu latory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the USEPA based on scientific data showing that they will not cause unreasonable risk s to human health or the environment when used as directed on produc t labeling. The registra tion 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 environm ent. Changes in scien ce, public policy, and pesticide use practices will occur over time. Th rough the registration review program, the agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Inform ation on this program is provided at http://www.epa.gov/oppsrr d1/registration_review/

. The agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registra tion review begin at 40 CFR 155.40. The agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the agency’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registrati on review decision. The TAED Preliminary Work Plan (PWP) wa s published on March 26, 2014 and the 60-day comment period ended May 26, 2014. Do cuments associated with this registration review can be viewed at http://www.regulations.gov in docket EPA-HQ-OPP- 2013-0608. Section 1.2 gives updates to the workplan and Tables 1 and 2 summarize the issues relevant to this registration review case and the anticipated registration review schedule.



## 1.2 Updates to the Work Plan
Since the publication of the PWP, the ag ency has made the following updates:

 Updated signature page, section 1.5, section 3, Table 5, and throughout the document to reflect a new biopesticide re gistration and tolerance exemption forDocket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 6 of 48 agricultural uses (r ice and strawberries) and resi dential uses on turf and nonbearing food crops, including the additi on of toxicological endpoints and points of departure.

 Updated section 1.5.3 to reflect current information regarding Design for the Environment (DfE).

 Updated Table 6 for guideline 850.4500 to refl ect the appropriate test substance.

 Updated Table 6 to remove guideli ne 835.4300 – Aerobic Aquatic Metabolism from the list of anticipated data needs. The HERA documents are expected to contain adequate fate data if a drinking water assessment is needed.

 Updated Table 10 to include MRID 49184701.

 Updated Appendix C1 to include an acceptable honeybee study.

 Deleted “Guidance for Commenters” s ection and added “Appendix E Response to Comments.”

 Corrected typographical and formatting errors.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 7 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 details)

Dietary (food) No 2014 None None

Dietary (drinking water) Yes 1 2014 Updated Developmental Toxicity – Rabbit Reproductive Toxicity Immunotoxicity

Occupational Handler Yes 1 None New Indoor Exposure Data – Dermal Indoor Exposure Data – Inhalation Developmental Toxicity – Rabbit Reproductive Toxicity Immunotoxicity

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 Immunotoxicity

Aggregate Yes 1 2014 Updated Developmental Toxicity – Rabbit Reproductive Toxicity Immunotoxicity

Cumulative No None None None

Tolerance Review No None None None

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

Environmental Fate Yes None New Aquatic exposure

1 . These assessments will be needed if new endpoints are select ed from the anticipated develo pmental, reproductive and immunoto xicity studies.

Table 2 – Anticipated Regi stration Review Schedule

Anticipated Activity Target Date

YYYY-MM-DD Completion Date

YYYY-MM-DD

Phase 1: Openin g the Docket

Open Docket and 60-Day Comment Period for Preliminary Work Plan 2014-03 2014-03-26

Close Public Comment Period 2014-05 2014-05-19

Phase 2: Case Development

Issue Final Work Plan 2014-09 2014-09Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 8 of 48 Issue Data Call-In (DCI) 2015-09

Receive Data to be Considered in Risk Assessment 2017-09

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2019-03

Close Public Comment Period 2019-04

Phase 3: Registration Review Decision and Implementation

Open 60-Day Public Comment Period for Proposed Decision 2019-09

Close Public Comment Period 2019-11

Issue Final Decision 2020-03

Begin Post-Decision Follow-up 2020

Total (years) 6

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



## 1.3 Chemical Identification and Properties
Table 3 presents the active ingredient to be a ssessed in case 5105: te traacetylethylenediamine (PC Code 004115). When activated using an oxyge n activator in the pres ence of water, TAED undergoes rapid perhydrolysis to yield peroxyacetic acid, which is being assessed under its 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 StructureDocket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 9 of 48 The tetraacetylethylenediamine product chemistry information relative to risk assessment is summarized in Table 4 and Appendix D.

Table 4 – Physical-Chemical and Environmental Fate Properties for TAED

Guideline No. Parameter TAED Physical/Chemical Properties 830.7000 pH 5 (3% solution); 5 (20 °C, 1g/l) 830.7050 UV/Visible Absorption TAED has a UV/VIS absorption maximum at 214 nm. 830.7200 Melting point ( o C) 147°C + 1°C 830.7300 Density Bulk density at 20°C is 430-520g/L 830.7370 Dissociation constant (pKa) Not applicab le because TAED has no dissociable groups.

830.7550 Octanol-water partition coefficient
at 25 o C (Log K ow ) Log Po/w:

− 0.06

830.7840 Solubility in water 2 g/100 ml at 20°C (20 g/L) 830.7840 Vapor pressure (mmHg) 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 pe r liter; mmHg = millimeters of mercury.



## 1.4 Use/Usage Description

1.4.1 Registrations There are three EPA-registered end use products (EPA Reg. Nos. 1043-125, 16930-5 and 88306- 3) that contain TAED as an active ingredie nt (a.i.). EPA Reg. N o. 1043-125 contains 61.6% TAED, EPA Reg. No. 16930-5 contains 11.9% TAED and EPA Reg. No. 88306-3 contains 19.99% TAED.

EPA Reg. No. 1043-125 is Part A of a two part syst em this is mixed with Part B (EPA Reg. No. 1043-124 which contains 1.0 percent hydrogen peroxi de) to create an end use hard surface disinfectant solution which, according to the label, contains approximately 0.085 percent peroxyacetic acid and 1.0 per cent hydrogen peroxide.

EPA Reg. No. 16930-5 is a solid formulation that contains TAED and another a.i. (sodium percarbonate). It is packaged in a capsule wh ich is loaded into in stitutional 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 and bleaching actions.” Hydrogen peroxide and peroxyacetic acid are being assessed under separate cases.

EPA Reg. No. 88306-3, the end use product, is a granular formulation upon tank mix of the initial active ingredient s. The product contains 19.99% TAED and two other active ingredients that are classified as biochemicals (sodium percar bonate and potassium silicat e). It is labeled for the early season control of b acterial and fungal pathogens on turf grass, golf courses, greenhouses and in nursery or in fiel d-grown rice and strawberries.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 10 of 48 

### 1.4.2 Summary of Registered Uses Table 5 presents a summary of the registered us es of TAED that will be assessed in this registration review.

Table 5 – Summary of TAED Registered Uses

Use Application Method Application Rate

Commercial Institutional and In dustrial 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 peroxy acetic acid B

Pre-clean and decontaminate criti cal or semi-critical medical devices prior to high level disinfection or sterilization. Immersion 0.085 percent peroxy acetic acid B

Biopesticide Agricultural/N onagricultural Use Sites
Early season control of bacterial and fungal pathogens on 1) field grown strawberries and rice, 2) seeds, plugs, and transplants of fruiting vegeta bles and crucifers, and 3) ornamentals and grasses grown for seed and sod production Conventional spray application equipment (air and ground) and

irrigation systems 0.3 lbs DAED/acre D

Early season control of bacterial and fungal pathogens on nonbearing fruit and nut trees Conventional spray application equipment (air and ground) and

irrigation systems 0.6 lbs DAED/acre E

Control of bacterial and fungal pathogens on golf course turfgrass and turfgrass in pa rks, sports facilities, and landscapes Conventional ground spray application equipment and irrigation systems 0.26 lbs DAED/acre F

A. Based on the label application rate of 3 oz EPA Reg. No. 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 applica tion. The label does not mention spray application. D. Based on the label application rate of 3 lbs EPA Reg. No. 88036-3 per acre E. Based on the label application rate of 6 lbs EPA Reg. No. 88036-3 per acre F. Based on the label application rate of 2.6 lbs EPA Reg. No. 88036-3 per acre



### 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 products that cont ain TAED. These products include dishwashing detergents. According to HERA (2002), 61,000 tons were consumed in the household detergents in the European Union in 2000.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 11 of 48 

## 1.5 Regulatory History
Registered products containing TAED date back to 1968. In 2012, a new registration was approved, with a variety of uses as outlined in Table 5. In 2014, a new registration was approved for agricultural/nonagricultural uses as a biopesticide (see Table 5).



### 1.5.1 Recent Regulatory Actions The Biopesticide and Pollution Prevention Divisi on (BPPD) registered a product containing the active ingredient TAED in August 2014.



### 1.5.2 Tolerance Information An exemption from the requirement of a tolera nce for residues of TA ED (and its metabolite DAED) in or on rice and strawberries has re cently been reviewed and established by the Biopesticides & Pollution Prevention Division (BPPD) (Tolerance Petition #3F8148, docket EPA-HQ-OPP-2013-0277, August 2014).



### 1.5.3 Design for the Environment TAED has been evaluated by the EPA’s Design for the Environment (DfE) program and is listed on DfE’s Safer Chemical Ingredie nts List (SCIL) as an Oxidan t/Oxidant Stablizer. DfE is a voluntary program that recognizes products that are high-performance and use the safest chemical ingredients. TAED is currently listed as a “yellow triangle” on SCIL meaning that the chemical has met DfE criteria for its functional ingredient-class, but has some hazard profile issues. Specifically, a chemical with this code is not associated with a low level of hazard concern for all human health and environmental e ndpoints. While it is a best-in-class chemical and among the safest available for a particular function, the function fulf illed by the chemical should be considered an area for safer chemis try innovation. The link to access TAED on the SCIL is: http://www.epa.gov/dfe/saferingredients.htm.



## 1.6 Incidents

1.6.1 Human Health
As of 03/18/2014, there are no TAED human poisoning incidents list ed in the OPP’s Incident Data System for the time period from 10/24/05 to 1/3/14.



### 1.6.2 Ecological There are no TAED fish or wildlife poisoni ng incidents in OPP’s In cident Data System.


## 2 Anticipated Data Needs

Table 6 presents a summary of th e studies anticipated as being needed to s upport this registration review. The agency is currently evaluating th e human health hazard da tabase 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 th e registrant for the studies anticipated as beingDocket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 12 of 48 needed provided that such waivers include a valid rationale of how the re gistration review could be conducted without the studies.Docket Number EPA-HQ-OPP-2013-0608www.regulations.govPage13of48Table 6 – Studies Anticipated as Needed forthe Registration Review of TAED and DAEDGLNStudy NameTest SubstanceTime Frame (Measuredin months from DCIReceipt)Risk Assessment(s) DataWill SupportUse Site(s) TriggeringAnticipated DataRequirementApplicable ExposureScenarioStudies Anticipated to be Required through the Registration Review DCI850.4500Algal toxicity -green algaeDAED degradate 24 Precautionary labeling All NA870.3700PrenatalDevelopmentalToxicity - RabbitTGAI 24Occupational HandlerResidential Post ApplicationHard surface disinfectant andwashing machine use See footnotes 1,2.870.3800Reproduction andFertility EffectsTGAI 24Occupational HandlerResidential Post ApplicationHard surface disinfectant andwashing machine useSee footnotes 1,2.870.7800 Immunotoxicity TGAI 24Occupational HandlerResidential Post ApplicationHard surface disinfectant andwashing machine useSee footnotes 1,2.875.1200Indoor Exposure –DermalTGAI or surrogate 24 Occupational Handler Hard surface disinfectant See footnote 1.875.1400Indoor Exposure -InhalationTGAI or surrogate 24 Occupational Handler Hard surface disinfectant See footnote 1.None Textile Leaching TGAI 24 Residential PostApplication Washing Machine See footnote 2.1Occupational handler scenarios include dermal and inhalation exposure during hard surface disinfection using mops and wipes ifnew toxicological endpoints are selected.2Residential post application scenarios include dermal and incidental oral exposure to laundered textiles.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 14 of 48 

## 3 Human Health Risk Assessment

The Agency anticipates the need to conduct a hu man health risk assessment for TAED. The most recent risk assessment was conducted in support of a new use in 2014. The Agency expects to require additional data for use in conducting the registration review. EPA does not anticipate the need to conduct human health risk assessments within this case for th e hydrogen peroxide or peroxyacetic acid generated by TAED because th ese chemicals are being evaluated by EPA as separate registrati on review cases.



## 3.1 Toxicological Endpoints
Toxicological endpoints and points of departure (POD) were last reviewed and selected for TAED to support a new direct food use registration (D410960) in 2014, as shown in Table 7

. Based on the data anticipated as being required to support this registra tion review, new endpoints and PODs may need to be established.

Table 7 – Existing Toxicol ogical Endpoints for TAED

Exposure Scenario Point of Departure Uncertainty/ FQPA Safety Factor (SF) RfD, PAD, Level of Concern for Risk Assessment Stud y and Toxicolo g ical Effects
Acute Dietary ( g eneral population, including infants and children and females 13-49 years of age) An acute endpoint was not selected based on the absence of an appropriate endpoint attributable to a single dose.

Chronic Dietar y (all population) NOAEL = 90 mg/kg/day UF A = 10X UF H = 10X FQPA = 10X cRfD = 0.09 mg/kg/day cPAD = 0.09 mg/kg/day 90 day oral study – rat LOAEL = 250 mg/kg/day based on significant increase in relative liver and testes weights in male rats.

Incidental Oral

Short-Term (1-30days) NOAEL = 90 mg/kg/day UF A = 10X UF H = 10X FQPA = 10X LOC for MOE = 1000 90 day oral study – rat LOAEL = 250 mg/kg/day based on significant increase in relative liver and testes weights in male rats.

Dermal

Short-Term (1-30 days) No clinical effect was observed at the highest dose tested (2000 mg/kg/day) in the available dermal study; therefore, no dermal risk assessment will be conducted.

Inhalation

Short-Term (1-30 days) No clinical effect was observed at the highest dose tested (99.7 mg/m 3 ) in the available inhalation study; therefore, no inhalation risk assessment will be conducted.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 15 of 48 

## 3.2 Dietary Exposure
A quantitative risk assessment was conducted by EPA for TAED in 2014 to assess potential dietary risks to support a new direct food use registration (D 410960). The dietary assessment focused on its use on rice and strawberries, in accordance with the associated tolerance exemption petition. DAED, a degradate of TAED, wa s identified to be th e potential residue for dietary assessment. On the basis of conversi on of TAED to DAED, EPA concluded that the toxicology data on TAED could be used for hazard characterization of DAE D and that “there is reasonable certainty of no harm to humans when exposed to residues of DAED from pesticidal use when label instructions are followed”.



### 3.2.1 Food
In its 2014 assessment, EPA concluded that human exposure to DAED, a degradate of TAED, is unlikely to occur via dietary exposure, when used according to label instructions, because TAED is used to control ear ly season fungus and bacterial diseas es on crops and the timing of its applications is well before harvesting occurs. Th ere are no direct or indi rect food uses for the antimicrobial uses of TAED. Therefore, the ag ency does not anticipate the need to update the dietary (food) risk asse ssment conducted in 2014.



### 3.2.2 Drinking Water
In its 2014 assessment, EPA concluded that the calculated percent of the chronic Population Adjusted Dose (%cPAD) based on dri nking water exposure, using DEEM-FCID TM Version 3.16, was well below the agency’s Level of Concern (LOC). Additionally, TAED is not directly added to any drinking water sources. Therefore, no risk of concern for drinking water was identified when TAED is applied directly on crops according to label instructions.

There are no direct drinking water uses for th e antimicrobial pesticide TAED. However, the approved use as a commercial laundry detergen t could potentially re sult in TAED being discharged into waste water and subsequently into surface water. Both of these exposure routes may potentially lead to indirect contamina tion to human drinking water. Based 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 new endpoints are selected from the anticipate d toxicity studies, the risks to human health from exposure to the final degradation produc t DAED in drinking water will need to be evaluated in an updated drinking water assessment.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 16 of 48 

## 3.3 Occupational and Re sidential Exposures

3.3.1 Occupational Exposures
Antimicrobial Uses
Occupational exposures are not anticipated for the commercial laundry use because the product is packaged as a capsule that is loaded in to the washing machines. Occupational handler exposures may occur, however, for the hard su rface disinfectant use in medical, dental and veterinary premises and equipment. These exposures will need to be asse ssed during registration review if endpoints are identified from the anticipated to be requi red toxicological studies. The occupational exposure scenario is listed in Table 8

. Table 8 – Occupational Exposure Scenarios for TAED

Handler Scenario Exposure Route(s) Duration

Hard surface disinfection using mops and wipes. Dermal Inhalation Intermediate Term

Occupational post applicati on exposures are not anticipated for the existing antimicrobial uses of TAED (hydrogen peroxide is being assessed in a se parate case).

Biopesticide Agricultura l/Nonagricultural Uses

Occupational exposures were not assessed in the 2014 assessment because endpoints for the dermal and inhalation exposure pathways were not identified (see Table 7).


### 3.3.2 Residential Exposures

Antimicrobial Uses

Residential handler exposures ar e not anticipated for TAED antim icrobial use because TAED is used only in institutional and industrial laund ries and medical/dental/v eterinary facilities. Residential post application exposures; however, ma y occur if TAED laundere d items are used in a residential environment. The residential exposure scenarios to be assessed during this registration review are listed in Table 9.

Table 9 – Residential Exposure Scenarios for the Antimicrobial Uses of TAED

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

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

Biopesticide Agricultural/Nonagricultural Use Sites

Residential incidental oral e xposures to children can occu r from the use of TAED as a biopesticide on turf. These expos ures occur through the hand to m outh, object to mouth and soil ingestion pathways and they were assessed in the 2014 assessment. This assessment used theDocket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 17 of 48 NOAEL of 90 mg/kg/day from a 90 day oral study in rats as a point of departure (see table 7). The individual MOEs range from 23,000 to 10,000,000 depending upon the exposure pathway. These MOEs are all greater than the target MOE of 1000 which m eans that the risks are not of

concern.



## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures In its 2014 assessment, EPA concluded that aggr egate risk from TAED was below the agency’s LOC. If new endpoints are selected from the an ticipated toxicity studies, EPA will update the aggregate assessment.



### 3.4.2 Cumulative Exposures With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common me chanism of toxicity, EPA has not made a common mechanism of toxicity finding as to TA ED, 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, ther efore, EPA has not assumed that TAED has a common mechanism of toxicity with other s ubstances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity a nd to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/

. 

## 4 Environmental Risk Assessment

The agency has not previously conducted an envi ronmental risk assessment for the antimicrobial uses of TAED. Because TAED is transforme d into peroxyacetic acid and hydrogen peroxide prior to or during application, any material go ing down the drain into wastewater treatment plants will be those moieties and their transfor mation products. Both peroxyacetic acid and hydrogen peroxide are active ingred ients in registered antimicr obial products that will be addressed separately in registration review. The degradate DAED also will be present when TAED is transformed. A European risk assessment 1 indicates that at least 97% of TAED and DAED would be removed during sewage plan t 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 envi ronment in Europe. Because the amount of TAED produced annually for pesticidal uses 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 during the year, the amount of e ither TAED or DAED entering the aquatic environment via waste water treatment plant di scharges is likely to be minimal.

1 HERA. 2002. Tetraacetylethylenediamine (TAED) (CAS 10543-57-4). Huma n & Environmental Risk Assessment on ingredients of European household cleaning products. December, 2002.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 18 of 48 

## 4.1 Environmental Fate Assessment
The agency will conduct an environmental fate assessment for TAED based on the current uses in industrial and institutional laundry facilities an d hard, non-porous surfaces in healthcare facilities, hospitals, medical, and dental offices. It serves as a bleach activator and reacts in aqueous solutions in the presence of an oxygen ac tivator, such as sodium percarbonate, to form the DAED degradate, hydrogen peroxide and per acetic acid using the perhydrolysis reaction. 2 Both peroxyacetic acid and hydrogen peroxide are highly-reactive and degrade rapidly.

Guideline environmental fate data that addr ess metabolism or transport of TAED in the terrestrial or aquatic environment have not b een submitted to the agency for TAED or its degradates. Although no data have been submitted, TAED and its degradates, TriAED (transient degradate) and DAED (terminal non-volatile degradat e), are 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 and in the HERA document. 4 The studies listed in the HERA document have not been formallyreviewed by the agency, but they indi cate that TAED is readily biodegradable 5 and highly removed in the activated sludge of a WWTP base d on a 97 percent removal rate in a porous pot
test. 6 The appropriate studies in the HERA docum ent will be formally reviewed by the agency for a final fate (exposure) assessment.

Parent TAED is miscible in water (20 g/L) 7 and its sequential degrad ates TriAED and DAED are expected to have similar water solubility base d 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. 8 However, in a washing machine study 9 using a formulated product which includes oxygen, TAED appears to degrade rapidly to form the degradate DAED at 30, 40, and 60 o C which represents cold, warm , and hot water temperatures, respectively. 10 The washing machine study, which is mo re environmentally-relevant than the abiotic hydrolysis study, has not been formally re viewed. It will be reviewed prior to conducting the risk assessment. The only detectable residue from the water in the washing machine was the DAED degradate. Appendix B contains additiona l 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

2 Reaction in water to release peroxyacetic acid and hydrogen peroxide

3 MRID 45299701

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 45299701Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 19 of 48 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 be cause it will not be sorbed to biosolids based on the log Kow of -0.06. 14 The registrants have not submitted any guideline studies on aerobic soil metabolis m (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 guide line data (OCSPP 835.1230) on sorption of TAED to soil. However, two unr eviewed 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 soil sorption studies will be reviewed by the agency prio r 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 wa ter 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 guideline studies for the biodegradat ion 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 th ey 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 of impairme nt for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 21 In addition, Total Maximum Daily Loads (TMDLs)

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

13 MRID 45299701

14 MRID 45299701

15 AISE, 1992 and Shell, 2000

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=885Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 20 of 48 have not been developed for TAED. 22 More information on impaired water bodies and TMDLs can be found at EPA’s website. 23



## 4.2 Environmental Exposure Pathways
As explained above under Environmental Risk Asse ssment, exposure to TAED is not anticipated due to its rapid dissociation into peroxyacetic acid and hydrogen peroxide. Exposure pathways for those active ingredients will be addressed in their registration review cases. As also discussed above, any degradates fo rmed are likely to be removed during sewage plant treatment. Therefore, the Agency does not expect TAED or it’s degradates to have any relevant environmental pathways leading to exposure of terrestrial or aquatic nontarget organisms.



## 4.3 Ecological Effects Assessment
Ecological effects data are used as measures of direct and indirect effects to aquatic and terrestrial organisms. Acute and chronic toxi city data from registrant-submitted studies conducted in accordance with the 850 OCSSP Harmoni zed Test Guidelines typically are used to evaluate the potential direct and indirect effects of a pesticide and its transformation products to plants and animals. Relevant data from the open lit erature also may be used to evaluate potential direct and indirect effects. As explained below, the agency antic ipates calling in data for algal toxicity for labeling purposes. No ecological risk assessment is planned for TAED per se, since the degradates are hydrogen peroxi de and peracetic acid which ar e being 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 ag ents that disinfect with corrosive action.



### 4.3.2 Measures of Effect (Ecotoxicology Endpoints) Ecotoxicity endpoints are used as measures of e ffects to assess acute and chronic hazards and risks to aquatic and terrestrial organisms. B ecause TAED is not expected to occur in the environment when used as directed on the produc t labels, only the basic f our ecotoxicity studies required for all antimicrobial active ingredients ar e needed for TAED. Three of the studies have been submitted. Only one of studies—algal toxicity, green algae—is anticipated to be required. Those studies are used to determine if precautiona ry 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 Toxic ity Test, Freshwater • 850.1010 Aquatic Invertebrate Ac ute Toxicity Test, Freshwater

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 21 of 48 • 850.4500 Algal Toxicity, Green Algae

The four submitted ecotoxicity studies categorize TAED as being practically nontoxic to birds, fish, and aquatic invertebrates and beneficial insects. More info rmation on these studies is found in Appendix C. The green algae toxicity study is a data gap. The agency has no ecotoxicity data for DAED but, as shown in Table 10, anticipates using available effects data from the open literature.

Table 10. Available Ecological Effects Endpoints for TAED

Receptor

Group Test Material Risk Scenario Toxicity Endpoint Reference

Freshwater fish TGAI Acute LC50 >140 mg ai/L 45274308

Chronic Not required NA

Freshwater invertebrates TGAI Acute EC50 >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 LD50>25 ug a.i./bee 49184701



## 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, available OPP models that estimate e xposures from discharges from wastewater treatment plants will be used to determ ine EECs in the aquatic environment.



## 4.5 Effects Analysis Plan
Besides the ecotoxicity data submitt ed by registrants, relevant data from the open literature also will be used to evaluate potential direct and in direct effects. Information on how the agencyDocket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 22 of 48 obtains and uses the open literature is presented on the agency’s website ( http://www.epa.gov/pesticides/s cience/efed/policy_guidance/team _authors/endangered_species _reregistration_workgroup/esa_ evaluation_open_literature.htm )


## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of registration decisi on for TAED, EPA reviewed these data and selected the most sensitive endpoi nts for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), TAED is subject to the endocrine screening part of the Endocrine Disruptor Screenin g Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the agency must scr een all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. 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 or likely endocrine disruptors.

For further information on the status of the ED SP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening ba ttery, please visit our website. 25

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 

## 6 Optional Label Changes

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



## 7 Next Steps

After the FWP is issued, the agency will continue it registration review by issuing a data call in designated in the TAED case.


## 8 References

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

U.S. Environmental Protection Agency (E PA). 2002. ECOTOX User Guide: ECOTOXicology Database System. Version 3.0. Availa ble: http://www.epa.gov/ecotox/. U.S. Environmental Protection Agency. High Pr oduction Volume Information System (HPVIS). http://www.epa.gov/hpvis/.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 24 of 48 

# Appendix A Toxicology Profile

A1 Acute Toxicity

The database for acute toxicity for TAED is cons idered complete. It co nsists of seven studies that have been submitted to EPA and these studies are listed in Table 1. These studies indicate that TAED 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 Irritation/

Rabbit 452997-02 Minimally Corrosive [Acceptable/Guideline] IV

870.2600 Dermal Sensitization/ Guinea Pig 452997-02 Not a dermal sensitizer [Acceptable/Non-Guideline] N/A

A2 Repeat Dose Toxicity

The database for repeat dose toxicity includes th ree 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 25 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 Rats 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 Rats MRID 45274305 0, 20, 200, 2000 mg/kg/day NOAEL = 200 mg/kg/day LOAEL = 2000 mg/kg/day based on centrilobular hypertrophy of the liver Oral (Gavage) Developmental Toxicity Study in Rats MRID 45299704 0, 40, 200, 1000 mg/kg/day Maternal NOAEL = 40 mg/kg/day
Maternal LOAEL = 20 0 mg/kg/day based on reduced body weight gain and food consumption
Developmental NOA EL = 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 Rats RCC,1989 0, 40, 200, 1000 mg/kg/day NOAEL = 200 mg/kg/day LOAEL = 1000 mg/kg/day, based on increased liver weight, slight hepatic centrilobular parenchymal hypertrophy
90 Day Gavage Study in Rats. Henkel, 1987 0, 90, 250, 800 mg/kg/day NOAEL = 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 Rats 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.

A3 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 26 of 48 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 regard ing mortality, clinical signs of toxicity, ophthalmology, and hematology. Significant dose -related decreases in body weight and body weight gain were observed in treat ed males at all dose levels and  500-mg/kg/day in treated females. Food consumption was de creased in treated rats but th e decreases reached statistical significance only in the 1000-mg/ kg/day males. Significant increa ses occurred in total protein (1000-mg/kg/day males and females), 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 incidences of grossly enlarged liver in 1000-mg/kg/da y 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 de generation of the seminiferous t ubules 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 dos e levels of 0, 40, 200 and 1000 mg/kg/day for 28 days. Mortality, clinical abnorma lities, ophthalmoscopic findings and toxicologically relevant changes of hematological, biochemical and urin alysis parameters were not observed throughout the study. Food consumption in male rats of the high dose group and female rats of the high and mid dose group was significantly less than the cont rols during treatment days 1 to 8. The same occurred in female rats of the high dose gr oup 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 peri od. A significant increa se of absolute and relative liver weights wa s found in male and female rats of the 1000 mg/kg/day group. Male rats of this group showed also significantly reduc ed absolute and relative spleen weights. Histopathological examination re vealed slight hepatic centril obular parenchymal hypertrophy, consistent with enzyme induction, in male a nd female rats of the high dose group. The lower dose levels produced no patholog ical evidence of toxicity.

Based upon the results a NOAEL of 200 mg/kg/da y was determined. The study was performed according to GLP standards and OECD guidelin e 407 and is therefore reliable without restrictions (data quality scor e 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 27 of 48 Henkel, 1987. Groups of 10 male and 10 female rats received TAED by gava ge at daily doses 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 c onsumption was not affected. Total body weight gain was decreased in male and fe male rats of all high dose groups.

Slightly decreased haematocrit va lues 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 the high dose group and increased cholesterol values in female animals tr eated 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 increase d in male rats. At 800 mg/kg/day absolute and relative liver weights of both sexes and relative adrenal and te stes weights in male rats were statistically significantly increa sed. No compound related macrosco pically visible findings were present at necropsy. Histopathol ogical 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 dos e group centrilobular hypert rophy was borderline in some rats and not considered a clear substance re lated effect, since this finding was also present in some control animals of the recovery group.

Definitive treatment-related adve rse effects occurred at the dose level of 800 mg/kg/day. Changes in organ weights were present at 250 mg /kg/day. No adverse effects were observed at 90 mg/kg/day. Hence, a “no-adve rse-effect-level” of 90 mg/kg/ day can be deduced. The study was performed according to OECD guideline 40 8 and GLP and is therefore reliable without restrictions (data quality score 1). This study is also acceptable under the analogous EPA guideline (OCSPP 870.3100).

2 Subchronic Inhalation Toxicity

Unilever, 1981 - Three groups of 12 male rats were e xposed in inhalation chambers to mean concentrations of TAED dust (< 3.5 μ m) 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. Following 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. There we re statistically significant increases in absolute and relative liver and kidney weights. All organ weights re turned to normal values following the recovery period, apart from a small increase in liver wei ght at the high dose. There was a statistically significant reduction in hemoglobin a nd an increase in platelet numbers in the rats exposed to the high level of TAED, and an in crease in the number of monocyt es in the high and mid-levelDocket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 28 of 48 exposure groups. These values were within norma l 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 a nd 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 alka line phosphatase activity in the high level group. The values had returned to normal after the reco very period. At post-mortem, one rat exposed to the high level of TAED had a sl ight 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 incr eases in kidney weights in the high and mid exposure groups, and in liver weights in all expo sure groups. This was reflected in changes in hepatic and renal morphology. The morphological ch ange 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 furt her ultrastructural studies that demonstrated proliferation of smooth endoplasmatic reticulum in these hepato cytes. The morphological changes found in the kidneys were eosinophilic droplets in the tubular epith elial cells, usually re ferred to as hyaline droplets composed principally of th e normal male rat urinary protein α 2 μ -globulin. The fact that in another Unilever study female rats fed TAED did not develop this pathology, but males did, confirms this to be the case (Carthew, 2001). Th e kidney findings are therefore specific to the male rat and not relevant to humans. Examinati on of recovery rats show ed that these effects reversed completely during a 13-week recovery period.

The NOAEL for systemic effects cannot be deri ved 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 conditions 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, respirat ory tract or nasal mucosa.

The study was conducted according to GLP standards and while the report does 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 qua lity score 2, assigned 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).

3 Subchronic Dermal Toxicity

MRID 452743-05 - TAED as a paste in 1% CMC was app lied daily to the shaved skin of ten rats/sex/dose at doses 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 weight or body we ight gain, food consumption, hematology, clinical chemistry, ophthalmology, organ weights, or gross necropsy fi ndings. 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 29 of 48 The LOAEL for systemic toxicity is >2000 mg/k g/day. The NOAEL for systemic toxicity is 200 mg/kg/day.

This study is Acceptable/Guidelin e and satisfies the guideline re quirement for a 90-day dermal toxicity study (OPPTS 870.3250 [§82 -3]; OECD 411) in the rat.

A4 Developmental Toxicity

This database for developmental toxicity co nsists of one study (MRID 45299704) and this study was done on the rat. The database for developmen tal toxicity is consider ed incomplete because only one species has been 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. Tr eatment-related effects at 1000 mg/kg/day included decreased body weight, body weight gain, co rrected body weight, corrected body weight gain, and food consumption. Treatm ent-related effects at 200 mg/kg/day were similar to those observed at the high dose a nd included decreased 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, co rrected body weight gain, and food consumption. The maternal NOAEL is 40 mg/kg/day.

Fetal toxicity was observed at 1000 mg/kg/day, with treatme nt-related effects including decreased mean fetal weights (male, female, and combined) and an increased incidence of skeletal variations. There were no treatment-rela ted 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 A cceptable/Guideline and satisfies the guideline requirements for a developmental toxicity study (OPPTS 870.3700 [§83-3a]; OECD 414) in rats.

A5 Reproductive Toxicity

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

A6 Neurotoxicity

There are no neurotoxicity studies available fo r TAED. The study is conditionally required per 40 CFR Part 158W if the neurotox icity screen in the 90 day oral rodent study or other data indicates neurotoxicity. Neurotoxi city has not been observed in the TAED toxicity studies and therefore the neurotoxicity study is not anticipated to be required for TAED.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 30 of 48 A7 Mutagenicity

Three mutagenicity studies have been submitted for TAED and the results are summarized in Table 3. TAED was negative for mutageni c effects in all three studies.

Table 3 – TAED Mutagenicity Studies

Study Type MRID Number Results

Ames assay 45274306 No evidence of mutageni city in strains TA98, TA100, TA1535, TA1537, and TA1538 (with or without S9) In vivo micronucleus
assay 45547202 No significant increase in frequency of micron nucleated PCEs at any dose level tested Human lymphocyte chromosome aberrations 45547201 No repeatable significant increases in either frequency of structural ab errations or frequency of polyploidy cells at any dose level tested.

A8 Chronic Toxicity and Carcinogenicity

There are no chronic toxicity or carcinogenicity studies avai lable for TAED; however, these studies are not needed for TAED because the us e pattern does not involve food exposure or long term occupational and residential exposure.

A9 Immunotoxicity

There are no immunotoxicity stud ies for TAED. According to subpart 40 CFR Part 158W and based on the existing toxicity database and use patte rn, this study is anticipated to be required for TAED registration review.

A10 Biotransformation

A biotransformation study fo r 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 ma le and 3 female Wistar rats after oral intubation with 0.5 ml diet ary 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 a nd 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-dos ing, more than 50% of the administered 14 C had been absorbed 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 levels rose during the 7 hours post-dosing. More than 90% of the urinary 14 C was excreted within 24 hours of dosing.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 31 of 48 Chromatographic analysis showed only traces of TAED in the urine. Most of the 14 C was excreted as triacetyl ethylene diamine (Tri AED) and diacetyl ethylen e diamine (DAED). Mono acetyl ethylene diamine (MAED) and ethylene diamine were not found.

The results show that TAED was rapidly abso rbed from the rat intestine and was largely metabolized and excreted in the urine with in 24 hours. Differences in the levels of 14 C recovered as expired CO 2 reflect the different metabolic fates of th e acetyl and ethylene diamine moieties.
The 14 C compounds identified in the ur ine, TriAED and DAED, indicate that deacetylation was the main metabolic route for TAED in the rat.

A11 Dermal Penetration

A dermal penetration study for TAED (Un ilever, 1978b) is include d 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 μ g TA[ 14 C]ED applied over 10 cm 2 of clipped dorsal skin. A second group was treated with 200 μ l of a solution containing 6% powder detergent B base, 1% perborate and 0.5% TA[ 14 C]ED (1348 μ g TA[ 14 C]ED) and a third group was treated with 50 μ l chloroform containing 1124±40 μ g TA[ 14 C]ED. The amounts of TA[ 14 C]ED penetrating the skin measured. Of the TA[ 14 C]ED which penetrated the skin, most was recovered in the urine while less than 3% was recovered in the feces. The re sults indicate that TAED can penetrate rat skin depending on contact time, with increased contact time leading to increas ed skin penetration.

A12 Data Gaps :
According to subpart 40 CFR Part 158W and ba sed on the existing toxicity database and use pattern, the following data re quirements apply to TAED.

1) Immunotoxicity

2) Reproduction toxicity

3) Developmental toxicity (non-rodent)Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 32 of 48 A13 Open Literature References 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: Tetraacetylenedia mine (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 N o. 233820 (Cited in HERA, 2002).

Unilever, 1978a. Unilever’s Toxicology Lab. Tetra acetyl ethylene diamine (TAED): Oral absorption, 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. Document 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 - Unilever 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. (Cited in HERA, 2002).Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 33 of 48 

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of TAED and its Degradates TriAED and DAED and Perhydrolysis Products Per oxyacetic 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 an d hard, non-porous surfaces in healthcare facilities, hospitals, medical, and dental offices. It serves as a bleach activator and reacts in aqueous solutions in the presence of an oxygen activator to form the DAED degradate, hydrogen peroxide and peracetic acid us ing the perhydrolysis reaction 26 . Both peroxyacetic acid and hydrogen peroxide are highly-react ive and degrade rapidly.

Guideline environmental fate data that addr ess metabolism or transport of TAED in the terrestrial or aquatic environment have not b een submitted to the agency for TAED or it’s degradates. Although no data have been s ubmitted, TAED and the degradates, TriAED (transient degradate) and DAED (terminal non-volat ile degradate), are exp ected to partition to water in the presence of sl udge based on a log Kow of -0.06. 27 Several studies are present in the literature and in the HERA document. 28 The studies listed in the HERA document have not been formally-reviewed by the agency, but they in dicate that TAED is readily biodegradable 29 and highly removed in the activated sludge of a WWTP based on a 97 percent removal rate in a porous pot test. 30 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 degr adate DAED, which can reach surface water if they pass through a WWTP.

Parent TAED is miscible in water (20 g/L) 31 and its sequential degr adates TriAED and DAED are expected to have similar water solubility based on struct ural 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. 32 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 33 which represents cold, warm, and hot water temperatures, respectively. 34 The washing machine study, which is more environmentally-

26 Reaction in water to release peroxyacetic acid and hydrogen peroxide

27 MRID 45299701

28 Human & Environmental Risk Assessment, http://www.heraproject.com/files/2-F-04- HERA%20TAED%20full%20web%20wd.pdf

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

30 Clariant, 2002

31 MRID 45299701

32 MRID 46335801

33 MRID 46335802, study not reviewed

34 http://housekeeping.about.com/od/laundry/a/laundry_h20temp.htmDocket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 34 of 48 relevant than the abiotic hydrolysis study, has not been formally-reviewed. It will be reviewed prior to conducting the risk a ssessment. The only detectable residue from the water in the washing machine was the DAED degradate.

Water and Sediment

Hydrolysis

The only submitted guideline environmental fate study on TAED is hydrolysis (MRID 46335801) 35 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 pa rent compound by 180 days and did not degrade in the study.

The agency also had access to a wash water study that used TAED (MRID 46335802) 36 . At 30

o C (86 o F), 40 o C (104 o F), and 60 o C (140 o F), parent TAED dissipate d by the end of the wash cycle and the only residue remaining was the degradate 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. 37 The lack of degradation of the DAED degrad ate was consistent with the results of the hydrolysis study, and DAED is the residue to wh ich the microorganisms in a WWTP would be exposed.

The abiotic hydrolysis study and the washing ma chine study show apparently contradictory results because the tested materi als were different. However, the abiotic hydrolysis study used parent TAED without an oxygen activator and th e washing machine study used a formulated product with an oxygen activator which promotes the perhydrolysis of parent TAED to form DAED and peroxyacetic acid.

Aqueous Photolysis

The registrant has not submitted any photodegr adation in water (835.2240) or photodegradation on soil (OCSPP 835.2410) data for TAED or its de gradates. However, based on the limited sorption of UV light 38 , these data are not required becau se the study would not provide any meaningful results.

35 MRID 46335801, find review date

36 MRID 46335802 not formally-reviewed

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

38 MRID 45299701Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 35 of 48 Octanol-Water Partition Coefficient

The octanol water coefficient (Log Kow or Log P) is -0.06 39 , 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 studies 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.

Anaerobic 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 sorp tion would indicate littl e/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 st udies (AISE, 1992, Shell, 2000) for TAED and AISE, 1992 for DAED. These studies indicate that sorption to soil is 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 wa ter 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 83 5.4100) have been submitted, and none are anticipated to be required. Based on the curren t uses, TAED is not li kely 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.

Anaerobic Soil Metabolism

No data on anaerobic soil metabolism (OCSPP 835.4200) have been submitted, and none are anticipated to be required. Based on the curren t uses, TAED is not li kely to be reach soil

39 MRID 45299701Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 36 of 48 because of limited sorption to activated sludge or to be sorbed to soil based on the AISE (1992) and Shell (2000) studies cited above.

Fate and Transport in WWTP

Activated Sludge Sorption Isotherm

Data on sorption to activated sl udge 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 are miscible in water 40 and are expected to partition to water in the presence of sludge based on a log Kow of -0.06. 41 The Agency has not received any submitted guideline studies for the biodegradation of TAED, but several studies are present in the literature and in the HERA document. 42 The studies listed in the HERA document have not been formally reviewed by the ag ency, but they indicate that TAED is readily biodegradable 43 and highly removed in the activated sludge of a WWTP based on a 97 % removal rate in a porous pot test. 44 The Agency has not formally reviewed these studies but will review them before conducti ng the final risk assessment.

Hydrogen Peroxide

Based on information from the open literature and the peroxy compounds, RED and registration review, under abiotic co nditions, 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 c oncentration. 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. Hydroge n peroxide is not expected to pose any concerns for surface water runoff.

Under aerobic aquatic metabolism conditions, hydrogen peroxide degr ades with half-lives of 1.1- 5.3 hours in non-sterile conditions, and ca . 80 hours in sterile conditi ons. Under anaerobic soil metabolism conditions, hydrogen peroxide degrades with a half-life of ca . 4 hours in samples of nine petroleum-contaminated surface soils from fi ve different states. Th e texture and pH of the soil, as well as the experimental temperature, di d not affect the degrada tion process; however, the organic carbon content of the soil did affect the degradation. Under aerobic soil metabolism conditions, hydrogen peroxide degr ades 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.

There are no data on the mobility of hydrogen peroxide in regards to either adsorption/desorption

40 MRID 45299701

41 MRID 45299701

42 Human & Environmental Risk Assessment, http://www.heraproject.com/files/2-F-04- HERA%20TAED%20full%20web%20wd.pdf

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

44 Clariant, 2002Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 37 of 48 (to determine K d ) with various soils or soil column leachin g. However, it is assumed that, since hydrogen peroxide has physical properties that ar e similar to water, hydrogen peroxide will not bind to soils.

The agency does not have data on hydrogen pero xide bioaccumulation in aquatic organisms. However, hydrogen peroxide is not expected to bioaccumulate due to its low octanol-water partition coefficients (0.40).

The average degradation half-life for hydrogen pe roxide in the atmosphere is 24 hours.

Peroxyacetic 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 containi ng 0.01 mol/L, the half-lives were 107, 109, and 112 hours for pH values of 4, 7, and 9, respectiv ely. 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, suspe nded matter, or biota. In the OECD Closed Bottle Test with adapted bacteria , peroxyacetic acid (initia l concentration of 2-5 mg/L) was highly biod egradable (>79%).

The hydrolysis products of per oxyacetic acid (acetic acid and hydrogen peroxide) are readily biodegradable. Th e biodegradation/DT 50 of peroxyacetic acid is rapid (not defined). The ready biodegradation of peroxyacetic acid is >70%. In soil, diluted peroxyacetic acid is rapidly and easily degraded via hydrolysis and instantaneously degraded via transition metal decomposition. At low concentrations, biodegradation could cont ribute to the degradati on 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 st udied in an unspecified soil. At 5 minutes post-treatment, 21.5% of the peroxyacetic aci d was recovered, 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 column 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 peroxide and acetic acid, are of low molecular weight, high water solubility, low fat solubility, and have no tendency to bioaccumulate.

No photodegradation in water, photodegradati on in air, anaerobic soil metabolism or accumulation studies in aquatic non-target organi sm’s information were found for peroxyacetic acid.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 38 of 48Docket Number EPA-HQ-OPP-2013-0608www.regulations.govPage39of48Table B1. Chemical, Physical, and Environmental Fate Properties of TAED andits degradates/metabolites TriAED andDAEDTAED TriAED DAEDGuideline Guideline(OCSPPnumberunlessspecified)Unit Source/Comment (MRIDNumber)CAS No. None None 10543-57-4 None None NoneMolecularformulaNone None C10H16N2O4C8H14N2O3C7H14N2O2NoneSmiles code None None O=C(N(C(=O)C)CCN(C(=O)C)C(=O)C)CO=C(NCCN(C(=O)C)C(=O)C)C O=C(NCCN(CC(=O)C))C NoneMolecularweightNone g/mol 228.25 186.21 158.20 NoneMelting point 830.7200oC 147 + 1No data, but expected to be similarbased on structural similarityNo data, but expected to be similarbased on structural similarity45299701Boiling point 830.7220oC Not applicable because it is a solid atroom temperatureNo data, but expected to be similarbased on structural similarityNo data, but expected to be similarbased on structural similarity45299701Watersolubility830.7840 g/l 2 (20oC)Miscible in waterNo data, but expected to be similarbased on structural similarityNo data, but expected to be similarbased on structural similarity45299701VaporPressure (mmHg)830.7950 mmHgNo data No data No data Not applicableHenry’s Law None atmm3mol-1Not expected to be volatile fromwater into air based on miscibility inwaterNo data, but expected to be similarbased on structural similarityNo data, but expected to be similarbased on structural similarityNot applicableDocket Number EPA-HQ-OPP-2013-0608www.regulations.govPage40of48TAED TriAED DAEDGuideline Guideline(OCSPPnumberunlessspecified)Unit Source/Comment (MRIDNumber)Log P (logKow)830.7550 Unitless-0.06 No data, but expected to be similarbased on structural similarityNo data, but expected to be similarbased on structural similarity45299701Hydrolysis 835.2120 Days 40 120 Stable 45299701pH 7, 15oCPerhydrolysisin WashingProcessNone Min 3 <5 Stable Gilbert, 1992,Buecking,19904523oC, pH 10.1Photodegradation in water835.2240 Days Not expected to photodegrade basedon limited UV light sorption from290-800 nmNo data, but expected to be similarbased on structural similarityNo data, but expected to be similarbased on structural similarity45299701Leachingadsorptiondesorption tosoil835.1230 ml/g Koc values 15-80 L/kg Nodata Koc value of 25 L/kg AISE, 1992,Shell, 2000 (forTAED)AISE, 1992 forDAED46Aerobicaquaticmetabolism835.4300 DaysNo data No data No dataNot applicable45Gilbert (1992) and Buecking (1990) havenot been reviewed by the Agency46Koc values from AISE (1992) and Shell (2000) have not been validated through Agency ReviewDocket Number EPA-HQ-OPP-2013-0608www.regulations.govPage41of48TAED TriAED DAEDGuideline Guideline(OCSPPnumberunlessspecified)Unit Source/Comment (MRIDNumber)Anaerobicaquaticmetabolism835.4400 DaysNo data No data No dataNot applicableActivatedsludgesorption835.1110 %,L/kgNo data No data No data Not applicableReadybiodegradability835.3110OECD301D% 52-56 % degradation in 28 days No data60 % degradation in 28 days Henkel, 197247Activatedsludgerespirationinhibition850.3300mg/l No data No data No data Not applicableBioconcentration in fish48850.1730 UnitlessNo data No data No data Not applicableBioconcentrationin aquaticorganisms is notlikely because ofthe low log Kowof -0.06 (<3)47Henkel (1972) has not been formally reviewed48BCF predictions should increase as the water solubility decreases and log Kow increases.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 42 of 48 References

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

AISE. October, 1992. Principles for Envi ronmental Risk Assessment of Detergent Chemicals in Europe; Outcome of 2 nd AISE Workshop, Limelette.

Buecking, H.W., Reinhardt, D., Lotsch, R., Zi emer, M., Pleschke, H. 1990. Environmental behavior and testing of the biodegradation of bleach syst ems, Commun. Jorn. Com. Esp. Deterg. 21: 167-182, ISSN 0212-7466.

Clariant (2002), GmbH, Division FUN, Tetr acetylethylenediamine – Water Solubility according to OECD 105, Report No H575, 2002-05-21.

Gilbert PA (1992). TAED – Tetraethylenediam ine. In: Hutzinger O (ed). The handbook of environmental chemistry. Springer-Verlag Be rlin Heidelberg, Volume 3 Part F p. 319-328.

Henkel (1972a). Henkel KGaA, TAED – Clos ed Bottle Test, OECD 301D, Report No. 0000749. Henkel (1972b). Henkel KGaA, DAED – Closed Bottle Test, OECD 301D, Report No. 1491.

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

Hoechst (1983). OECD 302B, Zahn-We llens-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: Determination of soil Sorption Coefficient (Koc), Report No. CSC 00349.

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

Unilever (1981a). TAED – Ready biodeg radability, Sturm Test, Study Report D87038.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 43 of 48 

# Appendix C Ecotoxicicology Profile

C1 Toxicity to Terrestrial Organisms

Birds

One acceptable acute-oral (LD50) study categorizes TAED as being practically nontoxic 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

One acceptable nontarget insect (LD50) study categor izes TAED as being practically nontoxic to adult honeybees via direct acute contact. The gui deline (880.4350) is satisfied. No additional nontarget insect toxicity data are anticipated to be needed.

Nontarget Insect Toxicity

Test Species Test Material

(% ai) Toxicity Toxicity

Category EPA Study

ID

Adult honeybee

( Apis mellifera L.) 99 Direct Acute Contact LD50 >25 ug ai/bee Practically nontoxic 49184701

Acceptable



### C2 Toxicity to Aquatic Organisms

Freshwater Fish

One available acute toxicity study (850.1075) categorizes tech nical-grade TAED as being practically nontoxic to freshwat er 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 44 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 acceptable acute toxicity study for the waterfl ea categorizes technical- grade TAED as being practically nontoxic to freshwat er invertebrates. The guideli ne (850.1010) for acute toxicity testing is satisfied. No additional aquatic inverteb rate toxicity data are anticipated to be needed.

Acute Toxicity to Freshwater Invertebrates

Test 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. B ecause TAED is not expected to occur in the estuarine/marine environment, data for es tuarine marine organisms are not anticipated to be needed.

Aquatic Plants

No data are available. A Tier II st udy (850.4500) is needed for green 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 properties of TAED.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 45 of 48 Appendix C References

45274309 Pedersen, C. (2000) Avian Acute Oral T oxicity Test With Tetraacetylethylenediamine in Bobwhite Quail: Lab Proj ect Number: 168-001-03. Unpublished study prepared by Bio-Life Associ ates, Ltd. 36 p. {OPPTS 850.2100}.

45274308 Sousa, J. (2000) Tetra Acetyl Ethyle ne 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 Ethylen e 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 46 of 48 

# Appendix D Product Chemistry

Tetraacetylethylenediamine (TAE D) product chemistry information is summarized in Table D1 (source: MRID No. 45299701).

Table D1 – Product Chemistry of TAED

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 stable to metals and metal ions under the conditions tested (room temperature and 54°C). The TAED technical is expected to be stable for at least one year stored away from sunlig ht 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 st able under accelerated storage stability conditions (i.e., at 54°C)

Stable at normal storage and handling conditions.

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

TAED is stable when dry at room temperatures.Docket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

Page 47 of 48 Guideline No. Physical and Chemical Properties Tetraacetylethylenediamine

830.6314 Oxidation/Reduction The product has no oxidizing or reducing potential because there are no reactive oxidizable/reducible groups in the compound. 830.6315 Flammability Not ap plicable because the produc t contains no combustible liquids. 830.6316 Explodability Not ap plicable because the prod uct 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 mercuryDocket Number EPA-HQ-OPP-2013-0608 www.regulations.gov

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# Appendix E Response to Comments

There were no comments posted in the docket for TAED.