Page 2 of 37 

### Table of Contents
1 Introduction

................................ ................................ ................................ ............................. 5
1.1 Statutory and Regulatory Authority

................................ ................................ ................. 5
1.2 Updates to the Work Plan

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

................................ ................................ ................................ ................. 7
1.4 Chemical Identification and Properties

................................ ................................ ............ 8
1.5 Use/Usage Description

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

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

................................ ................................ .................. 12
1.5.3 Usage Information

................................ ................................ ................................ .. 13
1.6 Regulatory History

................................ ................................ ................................ ......... 13
1.6.1 Recent/Pending Regulatory Actions

................................ ................................ ....... 13
1.6.2 Tolerance Information

................................ ................................ ............................ 13
1.7 Incidents

................................ ................................ ................................ ......................... 13
1.7.1 Human Health

................................ ................................ ................................ ......... 13
1.7.2 Ecological

................................ ................................ ................................ ............... 13
2 Anticipated Da ta Needs

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

................................ ................................ ........................... 18
3.1 Existing Toxicological Endpoints

................................ ................................ .................. 18
3.2 Dietary Exposure

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

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

................................ ................................ ................................ ....... 18
3.3 Occupational and Residential Exposures

................................ ................................ ....... 19
3.4 Aggregate and Cumulative Exposure

................................ ................................ ............. 20
3.4.1 Aggregate Exposures

................................ ................................ .............................. 20
3.4.2 Cumulative Exposures

................................ ................................ ............................ 20
4 Environmental Risk Assessment

................................ ................................ ........................... 21
4.1 Environmental Conceptual Model Exposure Pathways

................................ ................. 21
4.2 Ecological Effects Assessment

................................ ................................ ....................... 24
4.2.1 Mode of Action

................................ ................................ ................................ ....... 24
4.2.2 Measur es of Effect (Ecotoxicity Endpoints)

................................ ........................... 24
4.3 Exposure Analysis Plan

................................ ................................ ................................ .. 26
4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates

................................ ............ 26
4.3.2 Human Health Drinking Water Exposure Estimates

................................ .............. 27Page 3 of 37 4.3.3 Screening Level Down

- the

- Drain Analysis

................................ ............................ 27
4.4 Effects Analysis Plan

................................ ................................ ................................ ..... 27
5 Endocrine Disruptor Screening Program (EDSP)

................................ ................................ . 27
6 Next Steps

................................ ................................ ................................ ............................. 28
7 References

................................ ................................ ................................ ............................. 29

Appendix A T oxicology Profile

................................ ................................ ............................... 30 Appendix B Environmental Fate

................................ ................................ ............................. 33 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 34 Appendix D Comments Received Concerning the Preliminary Work Plan

............................ 37

List of Tables Table 1

- Summary of Anticipated Risk Assessments and Data Needs for the Trimethoxysilyl QACs

................................ ................................ ................................ ................................ ............... 6 Table 2

- Anticipated Registration Review Schedule

................................ ................................ ..... 7 Table 3

- Chemical Identification of Trimethoxysilyl QACs

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

- Physicochemical Properties for Trimethoxysilyl QACs

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

- Summary of Trimethoxysilyl QAC Registered Uses

................................ .................... 12 Table 6

- Studies Anticipated to be Needed for the Registration Review of Trimethoxysilyl QACs

................................ ................................ ................................ ................................ ............. 15 Table 7

- Occupational and Residential Exposure Scenarios for Trimethoxysily l QACs

............ 20 Table 8

- Selected Endpoints and Data Gaps for Risk Assessment of Trimethoxysilyl QACs

.... 24 Table 9

- Acute Toxicity Studies for Trimethoxysilyl QACs

................................ ....................... 30 Table 10

– Avian Toxicity

................................ ................................ ................................ ............ 34 Table 11

– Acute toxicity to freshwater fish

................................ ................................ ................. 35 Table 12

– Acute toxicity to freshwater invertebrates

................................ ................................ .. 35 Table 13

– Modeled toxicity data for alkyl quaternary ammonium surfactants

........................... 35

List of Figures Figure 1

- Conceptual model for environmental exposure to trimethoxysilyl QACs and its major degradates from indoor uses as a sanitizer and disinfectant, textile and plastic/rubber material preservative.

................................ ................................ ................................ ................................ .. 22 Figure 2

- Conceptual model for environmental exposure to trimethoxysilyl QACs and its maj or degradates from outdoor uses. (A) Aquatic exposure routes. (B) Terrestrial exposure routes.

.... 23Page 4 of 37 Human Health & Environmental Effects

William Hazel Nathan Mot tl Jonathan Chen Srinivas Gowda Najm Shamim William Erickson James Breithaupt

Risk Management Elizabeth Hernandez Lance Wormell

Office of General Counsel Philip RossPage 5 of 37 

## 1 Introduction

This document is the Environmental Protection Agency’s (EPA or “the agency”) Preliminary Work Plan (PWP) for the Trimethoxysilyl Quaternary Ammonium Chloride (QAC) Case . The PWP document explains what EPA's Office of Pesticide Programs knows about t rimetho xysilyl QACs , highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the agency in conducting the review, and providing an anticipated timeline for completing t rimethoxysilyl QACs’ review

. Initially, this Registration Review was scheduled to address only 1

- octadecana minium

- N, N

dimethyl

- N

- [3

- (trihydroxysilyl) propyl] chloride (PC code 107403 )

. However, because of their similar use p atterns as well as chemical, physical, toxicological, environmental fate, and ecotoxicity characteristics , this document also addresses three other silyl QACs: 1

- octadecanaminum

- N

- N

- dimethyl

- N

- [ 3

- ( trimethoxysilyl)propyl ] chloride (PC Code 107401) ; 1

- tetradecanaminum

- N

- N

- dimethyl

- N

- [ 3

- ( trimethoxysilyl)propyl ] chloride (PC Code 107409) ; and 1

- d ecanaminium

- N ,N

- didecyl

- N

- methyl

- N

- [ 3

- (trimethoxysilyl)propyl ] chloride (PC Code 169160 ). The September 2007 RED ( http://www.epa.gov/oppsrrd1/RED s/trimethoxysilyl

- quats

red.pdf ) addressed these simultaneously because of the similarities described above

. In light of the similarities described above, the agency is grouping these active ingredients together and merging them into the Trimethoxysilyl Q AC Registration Review case pursuant to 40 CFR Part 155.42(a) and 40 CFR Part 155.42(b)(4).
The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The agency intends, by sharing this information in the docket, to inform the public of what it knows about t rimethoxysilyl QACs and what types of new data or other information would be helpful for the agency to receive as it moves toward a decision on t rimeth oxysilyl QACs . The agency encourages all interested stakeholders to review the PWP and to provide comments and additional information that will help the agency’s decision

- making process for this chemical.



## 1.1 Statutory and Regulatory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United States generally must be registered by the U.S. Environmental Protection Agency (USEPA, EPA, or the agency ) based on scientific data sho wing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practice s change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the re gistration review program, the agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided at ht tp://www.epa.gov/oppsrrd1/registration_review/

.
The agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard forPage 6 of 37 registration. The regulations governing registration review begin at 40 CF R 155.40. The agency will consider benefits information and data as required by FIFRA. The public phase of registrati on 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 registration revi ew decision. After reviewing and responding to comments and data received in the docket during th is initial comment period, the agency will develop and commit to a F inal W ork P lan (FWP) and anticipated schedule for the Trimethoxysilyl QAC Case

. The Trimethoxysilyl Quaternar y Ammonium Chloride Preliminary Work Plan (PWP) was published on March 27, 2013 and the 60

- day comment period ended on May 28, 2013

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

- HQ

- OPP

- 20 13

- 0095
, EPA

- HQ

- OPP

- 20 13

- 0096 and EPA

- HQ

- OPP

- 20 13

- 0085

. Below is a summary of the issues relevant to this registration review case.

Table 1

- Summary of Anticipated Risk Assessments and Data Needs for the Trimethoxysilyl QACs

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 more detail about anticipated data needs)

Dietary (food) No (see 3.2.1) N/A N /A None

Dietary (drinking water) Yes (s ee 3.2.2 ) N/A N ew Two

- generation reproductive toxicity 1 Developmental toxicity 1

Occupational Handler Yes 2007 RED New Occupational exposure d ata Inhalation toxicity s tudy

Residential Handler Yes 2007 RED Updated Indoor exposure d ata Inhalation toxicity s tudy

Residential Post Application

- Incidental Oral and Dermal
, Inhalation No (see 3.3) N/A None None

Aggregate Yes N/A New Residential handler inhalation exposure Inhalation toxicity s tudy

Cumulative No (see 3.4) N/A N o None
Tolerance Review No (see 1.5.2) N/A New None

Ecological Yes N/A New Chronic daphnia study Aquatic plant toxicity Sediment toxicity Leaching from treated shingles and fascia board N/A = Not applicable

1 These studies are expected to be required but may be waived depending on the outcome of the required environmental fate studies. If the environmental fate studies reveal that human exposure via drinking water is negligible, a waiver may be justified.Page 7 of 37 Table 2

- Anticipated Registration Review Schedule
Anticipated Activity Target Date 2 Completion Date Phase 1: Opening the Docket Open Docket and 60

- Day Comment Period for Preli minary Work Plan 2013

- 03 2013

- 03

- 20 Close Public Comment Period 2013

- 05 2013

- 05

- 28 Phase 2: Case Development Issue Final Work Plan 2013

- 09 2013

- 0 9

- 1 2 Issue Data Call

- In (DCI) 2014

- 09 Receive Data to be Considered in Risk Assessment 201 6

- 09 Open 30

- Day Public Comment Period for Preliminary Risk Assessment(s) 2018

- 03 Close Public Comment Period 2018

- 04 Phase 3: Registration Review Decision and Implementation Open 60

- Day Public Comment Period for Pro posed Decision 2018

- 09 Close Public Comment Period 2018

- 11 Issue Final Decision 2019

- 03 Begin Post

- Decision Follow

- up 2019 Total (years) 6



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

• Clarified that there are no food uses for Trimethoxysilyl Quaternar y Ammonium Chloride pesticide products.

• Updated Table 6 to clarify those results from tests conducted according to OECD 443 3 or OCSPP Guideline 870.3800 can be submitted for consideration to address the Reproductive Toxicity Study requirement. Th is update was made in response to the
comment received during the public comment period (see A ppendix D )

.
• Corrected formatting and typographical errors

The Agency received one comment on the initial docket. The comment received did not a ffect the data needs , work plan and timelin e described in the PWP. The comment requested that the Agency consider the possibility that 870.3800 Two

- Generation Reproductive Study could possibly be addressed by testing results obtained from use of OECD guidelines. The Agency considered this possible approach and agrees that the OECD methods referenced in the comment could be considered for use in the subject te sting. The comment received and the Agency’s response is presented in Appendix D

. 

## 1.3 Case Overview

Initially, this Registration Review was scheduled to address only 1

- octadecana minium

- N, N

dimethyl

- N

- [3

- (trihydroxysilyl) propyl] chloride (PC code 107403 )

. However, because of their

2 The anticipated schedule will be re vised as necessary ( e.g ., on any need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case). 3 http://www.oecd

- ilibrary.org/environment/test

- no

- 443

- extended

- one

- generation

- reproductive

- toxicity

- study_9 789264122550

-
enPage 8 of 37 similar use p atterns as well as chemical, physical, toxicological, environmental fate, and ecotoxicity characteristics , this document also addresses three other silyl QACs: 1

- octadecanaminum

- N

- N

- dimethyl

- N

- [ 3

- ( trimethoxysilyl)propyl ] chloride (PC Code 107401) ; 1

- tetradecanaminum

- N

- N

- dimethyl

- N

- [ 3

- ( trimethoxysilyl)propyl ] chloride (PC Code 107409) ; and 1

- d ec anaminium

- N ,N

- didecyl

- N

- methyl

- N

- [ 3

- (trimethoxysilyl)propyl ] chloride (PC Code 169160 ). The September 2007 RED ( http://www.epa.gov/oppsrrd1/REDs/trimethoxysilyl

- quats

red.pdf ) ad dressed these simultaneously because of the similarities described above

. According to the 2011

- 2014 public Registration Review schedule, case 3148 and 5113 were p lanned to begin in fiscal year 2015

. To ensure the public is able to locate information asso ciated with case 3148, case 5100 and case 5113, EPA has created and will maintain a separate docket for each case. All EPA documents relevant to the three cases will be posted in all the three dockets.

This case will be referred to as the t rime thoxysilyl q uaternary ammonium chloride s (t rimethoxysilyl QACs)

. As a result of this grouping and merger, the t rimethoxysilyl QAC s case will now include:

1. Case 3148: 1

- Octadecanaminium

- N, N

- dimethyl

- N

- (3

- (trimethoxysilyl) propyl) chloride (PC code 107401 ) and 1

- Deca naminium

- N

- decyl

- N

- methyl

- N

- [ 3

- (trimethoxysilyl) propyl ] chloride (PC code 169160 )

.

2. Case 5100: 1

- Octadecanaminium

- N, N

- dimethyl

- N

- [3

- (trihydroxysilyl) propyl] chloride (PC code 107403 ); and

3. Case 5113: 1

- Tetradecanaminium

- N, N

- dimethyl

- N

- [3

- (trimethoxysilyl) propyl] chloride (PC code 107409 )

The docket s for the t rimethoxysilyl QAC (Case 3148 , Case 5100, Case 5113 ) has been established at http://www.regulations.gov in docket number EPA

- HQ

- OPP

- 2013

- 0095; EPA

HQ

- OPP

- 20 13

- 0096; EPA

- HQ

- OPP

- 20 13

- 0085

. 

## 1.4 Chemical Identification and Properties

Table 3 presents the four active ingredient s to be assessed in Case 3148 , 5100 and 5113 : 1

- Octadecanaminium

- N, N

- dimethyl

- N

- [3

- (trimethoxysilyl) propyl] chloride (PC Code: 107401 ), 1

- Octadecanaminiu m

- N,N

- dimethy l

- N

- [3

- (trihydroxysilyl)propyl] chloride (PC Code: 107403 ), 1

- Tetradecanaminium

- N,N

- dimethyl

- N

- [3

- (trimethoxysilyl)propyl] chloride (PC Code: 107409), 1

- Decanaminium

- N

- decyl

- N

- methyl

- N

- [3

- (trimethoxysilyl)propyl] chloride (PC Code: 169160 ). These four active ingredients are considered to be toxicologically and ecologically equivalent for the purposes of registration review; and except where otherwise noted, the four active ingredients in th ese case s will be referred to collectively as “ trimet hoxysilyl QAC s ”

.Page 9 of 37 Table 3

- Chemical Identification of Trimethoxysilyl QACs

Chemical Name 1

- Octadecanaminium, N, N

- dimethyl

- N

- [ 3

-

(trimethoxysilyl) propyl ]

- , chloride 1

- Tetradecanaminium, N, N

- dimethyl

- N

- [3

- (trimethoxysilyl) propyl]

- , chloride 1

- Decanaminium, N

decyl

- N

- methyl

- N

- [ 3

- (trimethoxysilyl ] propyl)

- , chloride 1

- O ct ade c a na mi n i um

- N
, N

- dim e t h yl

- N

- [ 3

- (tri h yd r o x y si l y l ) p r o p yl ]

- chloride

Common Name 3

- (trimethoxysilyl) propyl dimethyl octadecyl ammonium chloride Dimethyltetradecyl [3

- (trimethoxysilyl) propyl]

ammonium chloride N,N

- Didecyl

- N

- methyl

3

- (trimethoxysilyl) propanaminium chloride 3

- (trihydroxysilyl) propyl dimethyl octadecyl ammonium chloride

C lassifica

tion Silicone Quaternary Ammonium Chloride Salt

PC Code 107401 107409 169160 107403 CAS No. 27668

- 52

- 6 41591

- 87

- 1 68959

- 20

- 6 199111

- 50

- 7 Molecular Formula C 26 H 58 ClNO 3 Si C 22 H 50 ClNO 3 Si C 27 H 60 ClNO 3 Si C 23 H 52 ClNO 3 Si

Molecular Weight 496.30 g/mol 440.17 g/mol 510.31 g/mol 454.20 g/mol

Tolerances None None None None Incidents None None None None PC Code Molecular structures for the Tri m ethoxysilyl Quaternary Ammonium Chloride Compounds

107401

1

- Octadecanaminium, N,N

- dimethyl

- N

- [3 (trimethoxysilyl)propyl]

- , chloride

107403

1

- o ct ade c a na nm i n i um

- N
, N

- dim e t h yl

- N

- [ 3

- (tri h yd r o x y si l y l ) p r o p yl ]

- , chloridePage 10 of 37 107409

1

- Tetradecanaminium, N, N

- dimethyl

- N

- [3 (trimethoxysilyl)propyl]

- , chloride

169160

1

- Decanaminium, N

- decyl

- N

- methyl

- N

- [ 3

- (trimethoxysilyl)propyl ]

- , chloride

The t rimethoxysilyl QAC s product chemistry information relevant to risk assessment is summarized in Table 4 and details of the environmental fate properties are discussed in Appendix B

.

Table 4

- Physicochemical Properties for Trimethoxysilyl QACs

Guideline No. Physical and

Chemical Properties 1

- Octadecanaminium, N,N

- dimethyl

- N

- [ 3

-

(trimethoxysilyl) propyl ]

- , chloride 1

- Tetradecanaminium, N, N dimethyl

- N

- [3

-

(trimethoxysilyl) propyl]

- , chloride N,N

- Didecyl

- N

methyl

- 3

- (trimethoxysilyl) propanaminium chloride 1

- o c atde c a na m i n i um

N
, N

- dim e t h yl

- N

- [ 3

-

(tri h yd r o x y si l y l ) p r o p yl ]

- chloride

830.1650 Description of

Formulation

Process Confidential Business Information (CBI) CBI CBI CBI

830.6302

Color Pale yellow to off White Light brown Clear yellowish Light to dark a m ber Clear

830.6303 Physical State Liquid Liquid Liquid Liquid

830.6304

Odor Characteristic Silane odor Characteristic Silane odor Characteristic Silane odor Characteristic Silane odorPage 11 of 37 Guideline No. Physical and

Chemical Properties 1

- Octadecanaminium, N,N

- dimethyl

- N

- [ 3

-

(trimethoxysilyl) propyl ]

- , chloride 1

- Tetradecanaminium, N, N dimethyl

- N

- [3

-

(trimethoxysilyl) propyl]

- , chloride N,N

- Didecyl

- N

methyl

- 3

- (trimethoxysilyl) propanaminium chloride 1

- o c atde c a na m i n i um

N
, N

- dim e t h yl

- N

- [ 3

-

(tri h yd r o x y si l y l ) p r o p yl ]

- chloride

830.6313 Stability to normal and

elevated temperature, metals/metal ions Stable

830.6314 Oxidation/ Reduction: Does not contain oxidizing/reducing agents

830.7000 pH 5.3 to 6.9 at 20C (5% aqueous) 4.7(5% aqueous) 6.9 (5% solution) 6.91 (1% solution) 6.5

– 7.5

830.7050 UV/Visible Absorption Not applicable because the chemical structure shows that it wil l not absorb in the UV spectral region. No UV absorbing chromophore.

830.7200 Melting point Not applicable, it is a liquid.

830.7220 Boiling point 617° C (EPI Suite v4.1) 570 °C (EPI Suite v4.1) 628° C (EPI Suite v4.1) 702°C (EPI Suite v4.1)
830.7300 Density 0.841 to 0.859 g/ml 0.878 g/ml 0.865 g/ml 1.0 g/ml

830.7370 Dissociation

Constant in water As a cationic quaternary ammonium salt, it will completely ionize in an aqueous solution.

830.7550 Partition coefficient ( n

octanol/ water) Log K ow 4.90 (EPI Suite v4.1) 2.93(EPI Suite v4.1) 5.39(EPI Suite v4.1) 1.95 (EPI Suite v4.1)

830.7840 Solubility in
water At room temperature, the product is miscible in all proportions with water.

830.7950

Vapor pressure 5.8 x 10 - 14 mm Hg at 25°C (EPI Suite v4.1) 1.74 x 10 - 12 mm Hg at 25°C (EPI Suite v4.1) 2.46 x 10 - 14 mm Hg at 25°C (EPI Suite v4.1) 1.85 x 10 - 21 mm Hg at 25°C (EPI Suite v4.1)



## 1.5 Use/Usage Description

1.5.1 Registrations

There are 3 9 products containing 1

- Octadecanaminium, N,N

- dimethyl

- N

- (3

- (trimethoxysilyl) propyl)

- chloride (PC Code 107401) as an active ingredient. The percent active ingredient ( a

. i

. ) ranges from 0.5 percent to 84 percent and the formulations include liquid, soluble concentratePage 12 of 37 and ready t o use solution. There are 17 products containing 1

- Octadecanaminium, N,N

- dimethyl

N

- [3

- (trihydroxysilyl)propyl], chloride (PC Code 107403) as an a

. i

. The percent ai ranges from 0.75 percent to 35.6 percent and the formulations include liquid, soluble concentrate, flowable concentrate and ready to use solution. There is currently one product containing 1

- Tetradecanaminium, N
, N

- dimethyl

- N

- [3 (trimethoxysilyl)propyl]

- , chloride (PC Code 107409) as

an ai . The percent ai is 40 percent and is a liquid formulation. There is currently one active product containing 1

- Decanaminium, N

- decyl

- N

- methyl

- N

- (3

- (trimethoxysilyl)propyl)

- , chloride (PC Code 169160) as an ai

. The percent ai is 42 percent and it is a liquid formation.



### 1.5.2 Summary of Registered Uses

Table 5 presents a summary of the registered uses of t rimethoxysilyl QAC s that will be assessed in this registration review

. Trimethoxysilyl QAC products can be applied using the following applicatio n methods: fogger, pump sprayer, pressure sprayer, trigger spray bottle, dip treatment, brush treatment, sponge treatment, pad surface treatment, foam applicator, washing machine, vat soak, mechanical mixer, carpet steam cleaner, open pour, painting with b rush/roller and airless
sprayer, and placement of treated sponges for non potable water treatment.

Table 5

- Summary of Trimethoxysilyl QAC Registered Uses

Use Application Method Application Rate ( ai /wt of material, w/w)

Surface treatment of indoor nonfood contact organic and inorganic materials in homes and in commercial, industrial and institutional facilities such as wood, tile, glass, stone, bath rooms, floors, window sills, kitchens, etc

. F ogger, p ressure sprayer, pump

- up sprayer, carpet steam cleaner, dip treatment, brush, foaming apparatus, pad, trigger spray bottle 1,000

- 10,000 ppm

Surface treatment of o utdoor building materials including roofing and exterior walls made of wood, stone, brick, metal, tile, etc

. P ressure sprayer, pump

- up sprayer, dip treatment, pad, brush, foaming apparatus 1,000

- 10,000 ppm

Preservative treatment by incorporating into material during manufacture of paints, coatings, lattices, plastics, rubbers, grouts, mastics, emulsions, etc

. Mechanical mixer (open pour) 1,000

- 10,000 ppm

Textiles, fibers, and cordage in raw form or finished including fabrics, diapers, sheets, rugs, draperies, clothing, tents, rope, shoes, face gear, sails, upholstery, etc

. P ressure sprayer, pump

- up sprayer, dip treatment, pad, brush, foaming apparatus
, washing machine, carpet steam cleaner 1,000

- 10,000 ppm

Concrete (added in water when mixing concrete) Mechanical mixer (open pour) 1,000

- 10,000 ppm

Surfaces and fabrics in automobiles, taxis, recreational vehicles, etc . including tires P ressure sprayer, pump

- up sprayer, dip treatment, pad, brush, foaming apparatus 1,000

- 10,000 ppm

Air filters and materials, nonfood conveyor belts P ressure sprayer, pump

- up sprayer, dip treatment, pad, brush, foaming apparatus 1,000

- 10,000 ppm

Commercial and residential paint s Brush/roller and airless sprayer 1,000

- 10,000 ppmPage 13 of 37 

### 1.5.3 Usage Information

Usage information is not available for the t rimetho xysilyl QACs. T he Kline Biocides Report for 2004/2005 (Kline, 2005) does not include the t ri meth oxysilyl QAC s.


## 1.6 Regulatory History
The trimethoxysilyl QAC s are registered as bacteri o static, algistatic
, and fungistatic compounds. The first products containing 1

- Decanaminium, N

- decyl

- N

- methyl

- N

- [3

- (trimethoxysilyl] propyl)

- , chloride as an ai were registered in 1960. The first products containing 1

- Octadecanaminium, N, N

- dimethyl

- N

- [3 (trimethoxysilyl) propyl]

- , chloride as an ai were registered in 1992. The first products cont aining 1

- O ct ade c a na m i n i um

- N
, N

- dim e t h yl

- N

- [ 3

- (tri h yd r o x y si l y l ) p r o p yl ]

- chloride as an ai were registered in 2003. The first products containing 1

- Tetradecanaminium, N, N

- dimethyl

- N

- [3 (trimethoxysilyl) propyl]

- , chloride as an ai were registered in 2006.

The agency completed a Reregistration Eligibility Decision (RED) for Trimethoxysilyl Quaternary Ammonium Chloride in 2007. The post

- RED data call

- in (DCI) has not yet been issued.



### 1.6.1 Recent/Pending Regulatory Actions

There are no recent or pending regulatory actions for trimethoxysilyl QAC. EPA anticipates issuing the post

- RED data call

- in (DCI) in the near future.



### 1.6.2 Tolerance Information

There are no registered food uses for Trimethoxysilyl QACs pesticide products

. EPA has not established a tolerance or toleran ce exemption for residues of the trimethoxysilyl QACs in food. In addition, the Food and Drug Administration ( FDA ) has not established a food additive regulation and has not received a Food Contact Substance Notification for these compounds

. 

## 1.7 Incidents

1.7.1 Huma n Health

No t rimethoxysilyl QAC human poisoning incidents have been reported in OPP’s Incident Data System (IDS) from 1992 to the present

.


### 1.7.2 Ecological

No t rimethoxysilyl QAC ecological incidents have been reported in OP P’s Incident Da ta System (IDS) from 1992 to the present.


## 2 Anticipated Data NeedsPage 14 of 37 Table 6 presents a summary of the data anticipated as being needed to support this registration review.Docket Numbers EPA

- HQ

- OPP

- 2013

- 0095; EPA

- HQ

- OPP

- 20 13

- 0096; EPA

- HQ

- OPP

- 20 13

- 0085

www.regulations.gov

Page 15 of 37 Table 6

- Studies Anticipated to be Needed for the Registration Review of Trimethoxysilyl QACs

GLN Study Name Test Substance Time Frame (Months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data Requirement Applicable Exposure Scenario

Studies Anticipated to be Required through the Registration Review DCI Special Study 1 Special leaching study from roofing shingles and fascia board TGAI 2 12 Environmental fate Exterior surfaces (e.g., Treated shingles , walls, and fascia board ) Transport to the aquatic environment

835.1230 3 Leaching

- adsorption

desorption (batch equilibrium) TGAI 2 12 Environmental Fate Exterior surfaces (e.g., Treated shingles , walls, and fascia board ) Transport to the aquatic environment

835.4100 3 Aerobic soil metabolism TGAI 2 12 Environmental Fate Exterior surfaces (e.g., Treated shingles
, walls, and fascia board ) Transport to the aquatic environment

835.4 4 00 4 Anaerobic aquatic metabolism TGAI 2 12 Environmental Fate Exterior surfaces (e.g., Treated shingles , walls, and fascia board ) Transport to the aquatic environment

Special study Whole sediment chronic toxicity, freshwater invertebrate (2 species: an amphipod 5 and a chironomid 5 ) TGAI 6 12 Ecological Exterior surfaces (e.g., Treated shingles , walls, and fa s cia board ) Transport to the aquatic environment

Special study Whole sediment chronic toxicity, marine invertebrate ( an amphipod 7 ) TGAI 6 12 Ecological Exterior surfaces (e.g., Treated shingles , walls, and fa s cia board ) Transport to the aquatic environment

850.4400 850.4550 Aquatic plant toxicity ( non

- vascular ) 4 species: green algae, freshwater diatom 8

, saltwater diatom 8 , and a cyanobacteria 8 TGAI 6 12 Ecological Exterior surfaces (e.g., Treated shingles , walls, and fa s cia board ) Transport to the aquatic environment

850.4500 Aquatic plant toxicity (vascular) TGAI 6 12 Ecological Exterior surfaces (e.g., Treated shingles , walls, and fascia board ) Transport to the aquatic environment

870.3465 90

- day inhalation toxicity study TGAI 24 Occupational and Residential Indoor and outdoor use sites treated such that respirable aerosols are likely to be generated All scenarios below involv ing inhalation exposures (see 875.1300/875.1400)

.Page 16 of 37 GLN Study Name Test Substance Time Frame (Months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data Requirement Applicable Exposure Scenario

87 0 .3700b 9 Developmental Toxicity in Rabbits TGAI 24 Dietary (drinking water) Exterior surfaces (e.g., Treated shingles and fascia board ) Dietary exposures from drinking
water. 870.3800 9
, 11 Two

- gen reproductive toxicity study TGAI 24 Dietary (drinking water) Exterior surfaces (e.g., Treated shingles and fascia board ) Dietary exposures from drinking
water.

875.1300 875.1400 Outdoor or Indoor Exposure, Inhalation TGAI 24 Occupational and Residential Indoor and outdoor uses 10 Trigger pump sprayer, low pressure hand wand, high pressure hand wand, hand

- held fogger
, open pour , painting with brush/roller and airless sprayer.

875.1700 Product Use Information TGAI 12 Occupational and Residential All All above scenarios. Studies Expected to be Required through the Anticipated Post

- RED DCI 850.1010 Aquatic invertebrate acute toxicity, test, freshwater daphnids TGAI 12 Ecological Outdoor Transport to the aquatic environment

850.1075 Fish acute toxicity test, freshwater and marine TGAI 12 Ecological Outdoor Transport to the aquatic environment

1 Residues in treated shingles may leach upon contact with rainwater. Because the label (53053

- 8) is not specific about the types of shingles to be treated, results from each potential treatment material ( i.e ., asphalt, wood, etc .) are expected to be required to be submitted as well as results for wood used for fascia board. If the leaching data from treated roofing shingles and fascia board in this study indicate limited environmental exposure, then the agency would consider waiver requests for certain other anticipa ted environmental fate data requirements (GLN 835.1230, GLN 835.4100, GLN 835.4400, GLN 875.3700b, and GLN 870.3800)

. 2 Analytical monitoring would include both the parent and its alkyl quat ernary ammonium degradate.

3 Leached residues in treated shingles a nd fascia board may leach and move across lawns, where they have the potential for sorption and degradation in surface soil (835.1230). If the anticipated required soil/sediment sorption data indicate limited enviro nmental exposure, then anticipa ted data n eeds for aerobic soil metabolism (835.4100) may be waived. Aerobic soil metabolism (835.4100) represents the sum of hydrolysis and microbial degradation in surface soil that is non

- flooded and oxygenated.

4 Anaerobic aquatic metabolism represents the fate of a compound in suspended and bottom sediment in water bodies. If leaching from treated roof shingles and fascia boards is minimal and sorption to soil and sediment indicates limited release into water, then anticipated data needs for anaerobic aquatic me tabolism (835.4400) may be waived.

5 EPA has published the following guidance: Methods for Measuring the Toxicity and Bioaccumulation of Sediment

- Associated Contaminants with Freshwater Invertebrates, EPA 600/R

- 99/064 available on

- line at http://water.epa.gov/polwaste/sediments/cs/freshfact.cfm

. 6 TGAI will rapidly form an alkyl quaternary ammonium group and insoluble si l yl compounds by hydrolysis. Documentation of stab le concentrations during study should be on the alkyl quaternary ammonium portion , not the parent

. 7 EPA has published agency

- wide guidance: Method for Assessing the Chronic Toxicity of Marine and Estuarine Sediment

- associated Contaminants with the Amphipod Leptocheirus pl umulosus EPA 600/R

- 01/020 available on

- line at http://water.epa.gov/polwaste/sediments/cs/leptofact.cfm

.Page 17 of 37 8 If the anticipated testing shows green algae, Selenastrum capricornutum IC 50 a nd NOEC for trimethoxysilyl QACs are greater than 1.0 ppm or mg/L then anticipated aquatic plant testing for the freshwater diatom ( Navicula pelliculosa ), estuarine/marine diatom ( Skeletonema costatum ), and cyanobacteria ( Anabaena flos

- aquae ) may be waived

. 9 If the anticipated environmental fate studies reveal that human exposure via drinking water is negligible, this anticipated d ata requirement may be waived.

10 See Table 7 for specific exposure scenarios.
11 Results from a multi

- generation (EPA guideline 870.3800) or an extended one

- generation reproductive and fertility effects study using OECD TG 443 ( http://www.oecd

- ilibrary.org/environment/test

- no

- 443

- extended

- one

- generation

- reproductive

- toxicity

- study_9789264185371

- en ) may b e submitted for consideration in response to this requirement.Docket Numbers EPA

- HQ

- OPP

- 2013

- 0095; EPA

- HQ

- OPP

- 20 13

- 0096; EPA

- HQ

- OPP

- 20 13

- 0085 www.regulations.gov

Page 18 of 37 

## 3 Human Health Risk Assessment

The agency anticipates the need to conduct a human health risk assessment for t rimethoxysilyl QAC s . The agency expects to require additional data for use in conducting the registration review (see Table 6 )

. 

## 3.1 Existing Toxicological Endpoints
EPA has not previously identified t oxicological endpoints of concern for trimethoxysilyl QACs. The studies anticipated as being required through this registration review will allow the agency to establish the endpoints necess ary to conduct risk assessment.



## 3.2 Dietary Exposure

3.2.1 Food

Human diet ary exposure to trimethoxysilyl QAC residues is not expected to occur as there are no registered food uses. Approved uses involve preservation of materials and treatment of surfaces not intended for food contact. In addition, there are no oral hazard endpo ints of concern identified. Residue chemistry data are not expected to be needed. Because dietary (food) exposure is not expected, dietary risk assessments reflecting exposures to tri methoxysilyl QACs in food are not expected to be conducted.



### 3.2.2 Drinking Wate r EPA anticipates revisiting the need to conduct a drinking water assessment based on the results of the environmental fate and toxicity studies anticipated a s being required to support this registration review. As noted above, the trimethoxysilyl QACs are registered for preservation of materials and treatment of surfaces. Due to the potential for trimethoxysilyl QAC s to leach into water from treated materials and surfaces, there may be human exposure via drinking water. Treated materials and surfaces mu st be dried prior to their use which generally precludes pesticide residues from going down

- the

- drain . The trimethoxysilyl QACs form stable polymers that are also covalently bonded to the treated material (see Append ix B ) . Although some degradation and/or leaching from the treated material/surface may occur over time, the extent of such leaching is unknown . For this reason, environmental fate studies including two leaching studies, aerobic soil metabolism and anaerobic aquatic metabolism have been identified as being anticipated to be needed to support this registration review

. N o residue chemistry data are expected to be needed to characterize drinking water exposures

. However, depending on the outcome of the anticipated environmental fate studies and toxicity studies (if needed based on environmental fate studies) that become required , an oral hazard endpoint of concern may be identified. If th e anticipated environmental fate studies (particularly leaching) that become required indicate that contamination of drinking water is unlikely, the two toxicity studies may be waived

. If there is an oral hazard of concern and if exposure to tri methoxysily l QACs in drinking water is expected based on the new studies, a dietary drinking water risk assessment will be warranted

.Page 19 of 37 

## 3.3 Occupational and Residential Exposures

The agency anticipates the need to conduct occupational and residential assessments to support this registration review . Uses of t rimethoxysilyl QAC s that may result in occupational handler and residential handler/post application exposure are presented in Table 7

. At the time of the RED
, there were no toxicological endpoints of concern based on the review of the hazard data
set . As a result, o ccupational and residential risk assessments w ere not conducted to support the RED. D ermal risk assessment s were not conducted for short

- , intermediate

- , or long

- term exposure based upon the lack of any adverse systemic effects resulting from doses up to and including a limit dose (1000 mg/kg) from an adequate dermal toxic ity study. Although adverse systemic effects were not observed via other routes of exposure ( i.e

. , inhalation and incidental oral ingestion), the RED noted that the hazard database for these and other routes of exposure ( e.g ., dietary) was incomplete and not well characterized.
For registration revi ew, the agency does not anticipate the need to conduct a dermal risk
assessment or an incidental oral ingestion toddler assessment . This is due to the lack of adverse systemic effects in adequate oral developmental toxicity and dermal toxic ity stud ies at doses up to and including a limit dose of 1000 mg/kg/day in both studies . However, the agency cannot at this time adequately determine inhalation risk s to handlers due to the lack of an inhalation toxic ity study as well as inhalation exposure studies refle cting scenarios likely to generate aerosols such as fogging or painting with a brush/roller and an airless sprayer

. Therefore, the likely occupational and residential inhalation exposure scenarios for which risk assessments are needed have been identified in Table 7

.
The agency expects occupational and residential handler inhalation exposure from aerosolized sprays. Aerosolized spray may occur from treating textiles, carpets, roofing materials, tents, mattress pads, bathrooms, etc . via trigger pump spray
, pressure sprayer , or fogging

. P aint application using an airless sprayer and paint brush /roller would also generate aerosols. T he RED specified that the fogging use was to be removed from labels. However, a fogging use still remains on some EPA

- approved labels ( e.g

. , EPA Reg. Nos. 75174

- 2 and 83019

- 2). Unless labels are amended to remove the fogging use from the ir label s prior to risk assessment , the
agency intends to asse ss fogging use. Finally, the agency plans to assess inhalation exposure via
open

- pour, dipping, soaking and brushing applications as well. Occupational and residential inhalation post application exposure is expected to be negligible since the vapor pressure s of the
t rimethoxysilyl QAC s are very low ( all less than 1E

- 12 mm Hg ) (EPA, 2012)

.
Residential post application exposure of toddlers may occur via mouthing treated surfaces or clothing and toys made out of treated fabric. However, as no adverse effects were observed in either maternal or offspring rats in a n oral developmental toxicity study at a limit d ose of 1000 mg/kg/day
, toxicity via the oral route of exposure is very low; therefore, this scenario is not expected to be assessed (EPA, 2007)

. A listing of t rimetho xysilyl QAC exposure scenarios that will need to be assessed for registration review is in cluded in Table 7

.Page 20 of 37 Table 7

- Occupational and Residential Exposure Scenarios for Trimethoxysilyl QACs
Scenario Exposure Route(s) Duration Occupational Exposures Applying antimicrobial surface treatment using low pressure sprayer, trigger sprayers, sponge, brush and handheld fogger

. Inhalation Short and Intermediate Term

Applying paints (containing in

- can preservatives) using paint brush/roller and airless sprayer. Inhalation Short and Intermediate Term

Open pouring preservatives during manufacture of materials, dip treatments, concrete mixing, etc

. Inhalation Short and Intermediate Term

Residential Exposures Applying antimicrobial surface treatment to hard surfaces
, carpets , clothing, floors using low pressure sprayer , trigger sprayer, sponge, brush and handheld fogger. Inhalation Short and Intermediate Term

Applying paints (containing in

- can preservatives) using pa int brush/roller and airless sprayer. Inhalation Short and Intermediate Term



## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures

The agency anticipates conducting an aggregate assessment. Upon review of the required toxicity and exposure stud ies as well as reevaluation of existing studies
, human exposure
assessments via various sources and routes will be assessed for this registration review case . Any exposures expected to co

- occur will be aggregate d.



### 3.4.2 Cumulative Exposures

The agency does not intend to conduct a cumulative risk assessment. With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of tox icity finding as to the t rimethoxysilyl QAC s and any other substances and the t rimethoxysilyl QAC s do not appear to produce a toxic metabolite produced by other substances. For the purposes ofPage 21 of 37 this registration review, therefore, EPA has not assumed that t he t rimethoxysilyl QAC s ha ve a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the po licy statements released by EPA’s Office of Pesticide Programs at http://www.epa.gov/pesticides/cumulative/

. 

## 4 Environmental Risk Assessment

The agency has not conducted a n environmental risk assessment that supports a complete endangered species determination for the t rimethoxysilyl QACs. Outdoor applications of the trimethoxysilyl QAC to exterior walls, sidewalks, roofing and siding may result in movement of the ai into the aquatic envi ronment and exposure of terrestrial organisms

. Because the material will quickly sorb to aquatic sediment and is stable, benthic organisms may be additionally exposed via sediment contact and ingestion

. The risk assessment planned during regi stration revi ew will allow the agency to determine whether the use of these t rimethoxysilyl QACs has 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its de signated critical habitat, the agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate

. 

## 4.1 Environmental Conceptual Model Exposure Pathways

Based on the chemical/physical properties and environmental fate studies ( Appendix B ) and the uses in Table 5 , the agency has developed conceptual models for the environmental exposure to the t rimethoxy silyl QAC s and their degradates

. Figure 1 contains the conceptual model for the environmental e xposure from the indoor uses as a sanitizer and disinfectant
, and use s as a material preservative in textile s and plastic/rubber manufacturing process. Figure 2 contain s the conceptual model s for the outdoor /exterior use s o n walls, sidewalks, siding and roofing materials

. For the indoor and material preservative uses in Figure 1, all lines except for WWTP exposure are dashed indicating that the only potential exposure from these use patterns is to waste water treatment plants ( WWTPs ) and other exposures a re not expected. These use patterns have the potential for releases down

- the

- drain but releases from WWTPs to surface waters are expected to be highly unlikely due to sorption and precipitation occurring prior to reaching the WWTP and removal in biosolids at WWTPs ( Appendix B )

. The highest potential environmental exposure is based on the spray

- on application to exterior wall surfaces
, siding and roofi ng materials, which can result in leaching and runoff across la wns, sidewalks, and driveways

. Additionally, spray drift might result in off

- site drift adjacent to the application site and some potential exposure of terrestrial organisms

. For the outdoor us es in Figures 3 , the agency assumes that all routes of exposure are possible except for ingestion and bioconcentration by aquatic organisms and long

- range transport from spray drift

. Because of its electric charge and cell membrane activity, the major hydrolysis degradate, alkyl quat ernary ammonium cation
, is not expected to bioconcentrate in fish.Page 22 of 37 Figure 1

- Conceptual model for environmental exposure to trimethoxysilyl QACs and its major degradates from indoor uses as a sanitizer and disinfectant , textile and plastic/rubber material preservative

.

Stressor

Source

Receptors and Exposure Routes

Attribute Change(s) Individual organisms Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae Reduction in prey Modification of PCEs related to prey availability Habitat integrity Reduction in primary productivity Reduced cover Community change Modification of PCEs related to habitat Aquatic Animals Invertebrates Vertebrates Exposure Media

Ingestion Ingestion Uptake/gills or integument

Aquatic Plants Non

- vascular Vascular Uptake or sorption by

cells, roots, leaves,

Piscivorous* Invertebrates Vertebrates Phytoplanktivore/ Herbivore Invertebrates Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g ., amphibians, mollusks, crustaceans, etc .) Ingestion Waste Water Treatment Plant (WWTP)

Key Most likely

exposure pathway contributing to risk Low likelihood of contributing to risk In

- Service Use of Disinfectants or Sanitizers on Indoor Surfaces, Textile and Plastic/Rubber Material Preservative Use Sites

WWTP microorganisms Uptake or sorption

Population Respiration inhibition Waste Water Disposal Down

- the

- Drain

Surface Water

SedimentPage 23 of 37 Figure 2

- Conceptual model for environmental exposure to trimethoxysilyl QACs and its major degradates from outdoor uses. (A) Aquatic exposure ro utes. (B) Terrestrial exposure routes.

Stressor

Source

Receptors and Exposure Routes

Attribute Change(s) Application to Exterior Surfaces such as Sidewalks, Facades, and Roofing

Leaching/Run

- off

Individual organisms Reduced survival Reduced growth Reduced reproduction Food chain Reduction in algae Reduction in prey Modification of PCEs related to prey availability Habitat integrity Reduction in primary productivity Reduced cover Community change Modification of PCEs related to habitat Surface water/

Sediment Spray

- drift

Aquatic Animals Invertebrates Vertebrates Exposure Media

Ingestion Ingestion Long range atmospheric

transport

Wet/dry deposition

Uptake across gills or integument and/or sediment ingestion Aquatic Plants Non

- vascular Vascular Uptake or sorption by cell, roots, or leaves, Riparian plant terrestrial exposure pathways see

Figure ( B)

Piscivorous* Invertebrates Vertebrates Phytoplanktivore / Herbivore Invertebrates Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g .,amphibians , mollusks, crustaceans,, etc .) Ingestion Key Most likely

exposure pathway contributing to risk Low likelihood of contributing to risk (A)

Stressor

Source/ Exposure Media

Receptors and Exposure Routes

Attribute Change(s) Application to Exterior Surfaces such as Sidewalks, Facades, and Roofing

Spray Drift

Terrestrial insects

Individual organisms Reduced survival (emergence*) Reduced growth Reduced reproduction** Food chain Reduction in plant biomass Reduction in prey Modification of PCEs related to prey availability Habitat integrity Reduction in primary productivity Reduced cover Community change Modification of PCEs related to habitat Terrestrial plants Grasses/forbs, fruit, seeds, trees, shrubs Leaching

Terrestrial Animals Birds (Reptiles, Amphibians) Mammals Soil

Ingestion Ingestion Dermal uptake/ Ingestion Long range atmospheric transport

Root uptake Wet/dry deposition

Dermal contact Contact/Uptake leaves, stems

Beneficial Insects Reduced survival

*Refers to seedling emergence **Vegetative vigor and seedling emergence endpoints are assumed to be as sensitive or more sensitive than reproduction endpoint and plant reproduction s not explicitly evaluated. (B)

Key Most likely

exposure pathway contributing to risk Low likelihood of contributing to riskPage 24 of 37 

## 4.2 Ecological Effects Assessment
Ecological effects data are used as measures of direct and indirect effects to aquatic and terrestrial organisms

. Acute and chronic toxicity data from registrant

- submitted studies conducted in accordance with the 850 OCSPP Harmonized Test Guidelines will be used to evaluate the potential direct and indirect effects of the t rimethoxysilyl QAC to plants and animals

. Relevant data from the open literature available in ECOTOX also may b e used to evaluate potential direct and indirect effects

.


### 4.2.1 Mode of Action

Like other quat ernary ammonium compounds trimethoxysilyl QAC compounds are membrane

active agent s , causing leakage of intracellular molecules leading to death.



### 4.2.2 Measures of Effect (Ecotoxic ity Endpoints)

The available ecotoxicity data are summarized in Appendix C

. The agency uses the most sensitive endpoints for assessing acute and chronic risks to each receptor group shown in conceptual models (Figures 1 and 3) to be evaluated in the risk assessment

. Table 8 indicates the ecotoxicity data endpoints that will be used for the risk assessment and also indicates endpoints that are anticipated to be required but are n ot currently available.

Table 8

- Selected Endpoints and Data Gaps for Risk Assessment of Trimethoxysilyl QAC s Receptor Group Test Material Surrogate Species Risk Scenario Toxicity Endpoint Source

Freshwater fish TGAI 1 Rainbow trout Acute 96

- h LC 50 = 1.73 mg ai /L MRID 41001120

Chronic Data waived 2 NA

Freshwater invertebrates TGAI 1 Waterflea Acute 48

- h EC 50 = 0.17 mg/L MRID 00105187

Chronic Data required NA

Estuarine/marine fish TGAI 1 Fish Acute Data waived 3 NA

Chronic Data waived 3 NA

Estuarine/marine invertebrates TGAI 1 Shrimp (mysid) Acute Data required NA

Chronic Data waived 4 NA

Mollusk Acute Data required NA

Benthic invertebrates TGAI 1 Freshwater (1 chironomid sp. a nd 1 amphipod sp.) Chronic Data required NA

Estuarine/marine (1 amphipod sp.) Chronic Data r equired NA
Aquatic plants (nonvascular) TGAI 1 4 species 4 I C 50 and NOAEC Data required for 4 species
5 NA

Aquatic plants (vascular) TGAI 1 Duckweed I C 50 and NOAEC Data required NA

Birds TGAI Mallard Acute LD 50 > 159 0 mg ai /kg

- bw MRID 40385218Page 25 of 37 Receptor Group Test Material Surrogate Species Risk Scenario Toxicity Endpoint Source Dietary LC 50 >5620 ppm ai MRID 40385217

Chronic Data not required NA

Mammals TGAI Lab. rat

or mouse Acute LD 50 >5000 mg ai /kg

- bw MRID 40385201

Chronic NOAEL >1000 mg ai /kg

bw /day MRID 41339403

NA: not applicable

1 TGAI will rapidly form an alkyl quaternary ammonium group and insoluble silyl compounds by hydrolysis. Documentation of stable concentrations during study should be on the alkyl quaternary ammonium portion, not the parent.

2 More sensitive freshwater species appears to be the invertebrate, Daphnia magna

. Based on this relative toxicity and partitioning to sediment being the major exposure route, chronic testing with one species was considered sufficient to evaluate chronic r isks to freshwater animals

. Based on this relative toxicity and partitioning to sediment being the major exposure route data based on freshwater fish species was considered sufficient to characterize risk to estuarine/marine fish.

3 Toxicity for other alky l quaternary ammonium compounds ( e.g ., DDAC and DDACB) show toxicity to estuarine/marine fish are comparable to freshwater species

. 4 Based on the non

- specific mode

- of

- action and relative toxicity data for other alkyl ammonium compounds, chronic testing and the acute

- to

- chronic ratio derived from the freshwater invertebrate data will be used to characterize chronic risk for estuarine/marine invertebrates.

5 A test with a freshwater diatom, an estuarine/marine diatom, green algae, and cyanobacterium are an ticipated to be required. I f the green algae study demonstrates detrimental effects do no t occur at less than 1.0 ppm or mg/L, then the freshwater diatom, estuarine/marine diatom, and cyanobacteria data may be waived.

Freshwater Fish and Invertebrates

No a dditional data is required for freshwater fish. A chronic life cycle test for the daphnid is required because of the potential for chronic exposure from repeated applications and repeated rainfall events with associated leaching and runoff events. No chronic fish data is anticipated to be required because the more acutely sensitive freshwater taxon appears to be an invertebrate and given that sediment is expected to be the primary exposure route, chronic data for one species was considered sufficient

. Chronic risks to freshwater fish will be put into context of the freshwater invertebrate data, and if further refinement or characterization is needed information based on the relative toxicity and acute

- to

- chronic ratio of other quaternary ammonium compou nds can be used ( e.g ., DDAC 4 and DDACB 5 )

.
Estuarine/Marine Fish and Invertebrates

No additional acute or chronic data is required for estuarine/marine fish. Toxicity for other alkyl quaternary ammonium compounds show toxicity to estuarine/marine fish are c omparable to freshwater species (e.g., DDAC 3 and DDACB 4 ). Because sediment is expected to be the primary exposure route for the use patterns of concern , data for freshwater fish was considered sufficient to characterize risk to estuarine/marine fish. Based on other quaternary ammonium compounds (e.g., DDAC 3 and DDACB 4 ) and ecotoxicity models ( Appendix C ) for surfactants, mollusks may be more acutely sensitive to quaternary ammonium compounds than the other two required test species of a fish and a shrimp. An acute test with a mollusk is anti cipated to be needed to assess risk.

4 D idecyl dimethyl ammonium chloride , Case 3003, EPA docket EPA

- HQ

- OPP

- 2006

- 0338
5 Didecyl dimethyl ammonium carbonate and bicarbonate Case 5014, EPA

- HQ

- OPP

- 2012

- 0651Page 26 of 37 Aquatic Plants
An algal Tier II study is expected to be required for three aquatic non

- vascular species: one green algae ( Selenastrum capricornutum)
, one freshwater diatom ( Navicula pelliculosa) , one estuarine/marine diatom ( Skeletonema costatum ), and one cyanobacteria (Anabaena flos

- aquae ) species

. I f the green algae results demonstrate that detrimental effects do not occur at less than 1.0 ppm (mg/L), then the freshwater diatom, estuarine/marine dia tom, and cyanobacteria requirements would be waived. A Tier II study is expected to be required for one aquatic vascular species ( Lemna gibba ).

Sediment Toxicity

No data are available. Data are expected to be needed for freshwater and estuarine/marine bent hic invertebrates potentially exposed in sediment, because any leachate transported to the aquatic environment from outdoor applications to roofing , facades, sidewalks and siding will sorb to aquatic sediment

. The active ingredient is positively

- charged and the sediment is negatively

- charged. The negative electrical charge of the sediment will attract and sorb the positively

- charged active ingredient. One contributor to this aquatic exposure is impervious surfaces over which the runoff water will flow. Ac cording to “Using Smart Growth Techniques as Stormwater Best Management Practices,” the extent of impervious surfaces, primarily associated with vehicular traffic, is about 20, 38, and 65 % for 1, 4, and 8 houses/acre, respectively. 6 Another contributor to this aquatic exposure is that sorption to soil in lawns is not immediate and runoff to impervious surfaces can occur prior to sorption. The 835.1230 test guideline 7 states “an equilibrium period of 24 hours is generally sufficient” for sorption to

occur. 8

Based on the half life of the hydrolyzed transformation product (quate r nary ammonium group) being stable ( i.e ., >10 days), chronic rather than acute sediment tests are expected to be required. For freshwater organisms, testing is expected to be required w ith 1 chironomid sp. and 1 amphipod sp. For estuarine/marine organisms, testing is expected to be required with 1 amphipod species.



## 4.3 Exposure Analysis Plan

4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates

Available OPP models will be used to derive aquatic exposure estimates (EECs) for use in the risk assessment. Models are available to provide EECs for leaching of t rimethoxysilyl QAC s from applications to roofing and siding and for down

- the

- drain estimates for uses that discharge into waste water tr eatment facilities. For other uses for which models are not available, exposure estimates cannot be quantified but will be considered subjectively.

6 Using Smart Growth Techniques as Stormwater Best Management Practices, http://www.epa.gov/smartgrowth/stormwater.htm
7 OPPTS 835.1230. Adsorption/Desorption, Batch Equilibrium), http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0152

- 0006 8 835.1230, p. 18. An equilibrium period is the minimum time interval for soil and water concentrations to reach relatively constant values.Page 27 of 37 

### 4.3.2 Human Health Drinking Water Exposure Estimates

The agency does not expect significant contamination of drink ing water because the
t rimethoxysilyl QACs form polymer s that covalently bond to treated material and then degrade slowly to monomers (Green et al , 2011; de Buyl; see Appendix B )

. However, the rate of leaching from treated surfaces or materials is unknown. To determine the poten tial for human exposure to the t rimethoxysilyl QACs via drinking water, leachi ng studies a re anticipated to be required. Whether reproductive and developmental toxicity studies a re required and whether a human drinking water assessment is conducted will depend on the outcome of the environmental fate studies



### 4.3.3 Screening Level Down

- the

- Drain Analy sis No screening Down

- the

- Drain analysis was conducted because releases of t rimethoxysilyl QACs from WWTPs to the environment are not expected

. Gorman (1995) shows a hydrolysis study conducted on 3

- (trimethoxysilyl) propyl dimethyl octadecyl ammonium chloride (PC Code 107401) at pH 5, 7, and 9 that showed the half

- lives of this chemical at all three pHs were very short: at pH 5, the half

- life is 14. 6 minutes; at pH 7, the half

- life is 8 minutes, and at pH 9, the half

- life is 3.8 minutes. Thus, hydrolyt ically , the trimethoxysilyl QACs are unstable and degrade within an hour. The degradation process would include the fissure of silyl moiety group from the rest of the trimethoxysilyl QACs , instantly converting into silicate (which precipitates out) and alk yl quat ernary ammonium which will sorb to solids . The next step would be rapid degradation of alkyl groups (C 10 to C 14 ) on the alkyl quat ernary ammonium degradate and mineralization. Because of the inherent instability of the parent Trimethoxysilyl QACs an d sorption ( Appendix B ) and biodegradation of the alkyl quat ernary ammonium degradates
, insignificant or no exposure to the parent or its toxic degradates will result from the down

- the

- drain exposure pathway

. 

## 4.4 Effe cts Analysis Plan
In addition to the required 850 OCSPP guideline studies, open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database 9

. This database employs a literature search engine for locating chemical toxicity data for a quatic life, terrestrial plants, and wildlife. The ECOTOX database will be searched for trimethoxysilyl QACs and alkyl quaternary ammonium compounds when the risk assessment for the trimethoxysilyl QAC s is prepared. At that time, endpoints more sensitive t han what is currently known will be reviewed from the open literature studies. Data from the ECOTOX run for the t rimethoxysilyl QAC will be evaluated for possible quantitative and/or qualitative inclusion in the risk assessment in support of Registration Review.


## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potentia l adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and

9 http://cfpub.epa.gov/ecotox/ ECOTOX was created and is maintained by t he USEPA, Office of Research and Development, and the National Health and Environmental Effects Research Laboratory's Mid

- Continent Ecology Division.Page 28 of 37 chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of the 2007 RED for the t rimethoxysilyl QACs , EPA reviewed these data and sel ected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), t rimethoxysilyl QAC is subject to the endocrine screening part of the Endocrine Disruptor Screening P rogram (EDSP).
EPA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such e ndocrine effects as the Administrator may designate.” The EDSP employs a two

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

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

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

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredient s and 9 inert ingredients. T rimethoxysilyl QAC is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call

ins, requir ing the submission of EDSP screening assays for T rimethoxysilyl QAC

. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

. 

## 6 Next Steps

A DCI will be developed regarding the data needs listed under the “ Anticipated Data Needs” section of this document. The Agency expects to issue the DCI in September 201 4

. The Agency will conduct human health and e nvironmental fate and ecological hazard assessments for all

uses.Page 29 of 37 

## 7 References

Cornell University Cooperative Extension (2007). Cation Exchange Capacity Fact Sheet. http://nmsp.cals.cornell.edu/p ublications/factsheets/factsheet22.pdf
D. de Buyl (2007). Chapter 19. Organo

- Functional Silanes. Dow Corning Europe SA, Seneffe (Belgium)

EPA (2007). Reregistration Eligibility Decision for Trimethoxysilyl Quaternary Ammonium Chloride Compounds. EPA 739

- R

- 07

- 007
EPA, (2012). Standard Operating Procedures for Residential Pesticide Exposure Assessment. Health Effects Division. Office of Pesticide Programs. October, 2012.
Gorman, M. (1995) Hydrolysis of DC

- 5772 as a Function of pH: Amended Final Report: Lab Pr oject Number: 42160: 8253. Unpublished study prepared by ABC Labs, Inc. 202 p.

Green, J

- B.D., T. Fulghum, and M.A. Nordhaus (2011). Immobilized Antimicrobial Agents: A Critical Perspective. Science Against Microbial Pathogens: Communicating Current Researc h and Technological Advances, A. Mendez

- Vilas (Ed). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC380687/pdf/applmicro00052

- 0033.pdfPage 30 of 37 

# Appendix A 

# T oxicology Profile Acute Toxicity for Product Labeling

As listed in Table 9
, a cute toxicity data for a 50% formulation of 3

- (trimethoxysilyl) propyl dimethyl octadec yl ammonium chloride show low acute toxicity for single exposures by the oral, dermal, and inhalation routes (Categories I V, III, and I V respectively) . However, severe acute toxicity is observed with respect to skin and eye irritation of this active ingredient.

Table 9

- Acute Toxicity Studies for Trimethoxysilyl QACs
Guideline No./ Study Type MRID No. Results Toxicity Category 870.1100

(81

- 1) 40385201 Oral LD 50 > 5000 mg/kg IV

870.1200

(81

- 2) 40385201 Dermal LD 50 > 2000 mg/kg III

870.1300

(81

- 3) Not Available Inhalation LC 50 > 2.0 mg/L (1 Hour) 10 IV

870.2400

(81

- 4) 403385201 Severe irritant to ocular tissue I

870.2500

(81

- 5) Not Available Severe irritant to skin I

870.3250 41339403 Dermal and Systemic NOAEL > 1000 mg/kg/day Acceptable 870.3100 46280411 NOAEL ≥ 240 mg/kg/day (HDT) Acceptable

870.3700 41438003 Maternal and Developmental NOAEL ≥ 1000 mg/kg/day Acceptable

870.5100 46280412 No evidence of mutagenicity Acceptable 870.5300 46280413 No evidence of mutagenicity Acceptable

870.5375 46280414 No association with the induction of structural chromosomal aberration Acceptable

41296803 No evidence of compound inducted cytotoxicity Acceptable



## Subchronic Toxicity

There is one rat 90

- day dermal study (MRID 41339403) in the toxicology database and this study is summarized below. In the 90

- day s ubchronic dermal toxicity study, groups of 10 male and 10 female Sprague

- Dawley rats were treated with 3

- (trimethoxysilyl) propyl dimethyl octadecyl ammonium chloride (81.08%, Lot No. BN029263) at doses of 0, 100, 500, or 1000 mg/kg/day (doses based on range

- finding study MRID 41339402). A vehicle control group was

10 Although study duration was only one hour, the LC 50 exceeded the limit dose for acute inhalation toxicit yPage 31 of 37 treated with 1000 mg/kg/day propylene glycol and an additional sham control group was included in the study. Animals were treated by dermal occlusion for 6 hours/day, 5 days/week for 90 days. There were no treatment

- related deat hs or signs of systemic toxicity and no
treatment

- related effects on body weight, food consumption, hematology, and clinical chemistry

. 

## Developmental Toxicity

In a developmental toxicity study in rats (MRID 41438003), 3

- (trimethoxysilyl) propyl dimethyl octadecyl ammonium chloride (81.08% ai , in co rn oil) was administered by gavage to pregnant Sprague

- Dawley rats (25/sex/dose) on days 6 through 15 of gestation a t dose levels of 0, 100, 300, and 1000 mg/kg/day. Group mean liver weight was increased 6% in maternal animals at 1000 mg/kg/day compared to vehicle control. There was no significant treatment related effect on body weights or food consumption in maternal animals. There were no significant treatment related effects on cesarean section observations or on the incidence of fetal skeletal or soft tissue malformations or variations at any dose level. Although maternal liver weight was increased by 7% at the 1000 mg/kg/day dose, this effect was not accompanied by any other signs of liver toxicity, and is thus not considered treatment

- related. The maternal NOAEL is considered to be ≥ 1000 mg/kg/day, a nd the Maternal LOAEL is >1000 mg/kg/day. The developmental toxici ty NOAEL is considered to be ≥ 1000 mg/kg/day, and the de velopmental toxicity LOAEL is > 1000 mg/kg/day. This study is classified as acceptable and satisfies the guideline requirement (870.3700) for a developmental toxicity study in rats.

T his rat study was the only developmental toxicity study available for the t rimethoxysilyl QACs

. Although no evidence of increased susceptibility of offspring was observed following in utero exposure up t o and including a limit dose (1 000 mg/kg/day)
, a n additional developme ntal study in another species is anticipated to be needed to characterize the hazard of the t rimethoxysilyl QACs potentially associated with chronic dietary exposure via drinking water

. However, if the environmental fate studies (particularly leaching) that are anticipated to be required indicate that contamination of drinking water is unlikely, the second developmental toxicity study anticipated to be required may be waived. 

## Reproductive Toxicity

There is no reproductive toxicity study available . Howeve r, such a study is required to support

uses that may result in human exposure via food or drinking water

. As there is the potential for drinking water exposure to the trimethoxysilyl QACs, a two

- generation reproducti ve toxicity study is anticipated to be n eeded for registration review. However, if the environmental fate studies (particularly leaching) that are anticipated to be required indicate that contamination of drinking water is unlikely, the reproductive toxicity study anticipated to be required may be waived.Page 32 of 37 

## Chronic Toxicity

No chronic toxicity studies are available, but none are needed. The database for chronic toxicity is adequate given the limited potential for chronic or long

- term human exposures based on the approved uses of the t rimethoxysil yl QAC s

. 

## Carcinogenicity

There is no carcinogenicity stud y available, but none is needed. There are no concerns for carcinog enicity for the t rimethoxysilyl QAC s based on the results of the mutagenicity studies and the lack of any systemic toxicity being observed in studies comprising the existing toxicity database; therefore, no carcinogenic ity study is required

. 

## Mutagenicity

T he mutagenicity of the t rimethoxys ilyl QAC s is fully characterized. For all of the compounds covered under this Registration Review case , there are a total of four acceptable mutagenicity studies, all of which demonstrate that the t rimethoxysilyl QAC s are negative for mutagenicity



## Immunoto xicity

An immunotoxicity study is a data requirement for all antimicrobial pesticide chemicals under 40 CFR Part 158W, Data Requirements for Antimicrobial Pesticides. However, based on a weight of evidence approach, the agency concludes that immunotoxicity studies are not required for the Trimethoxysilyl QACs Registration Review case. There was no evidence of adverse effects on the immune system in the database for any of the trimethoxysilyl QACs. The trimethoxysilyl QACs do not belong to a class of chemica ls (e.g., the organotins, heavy metals, or halogenated aromatic hydrocarbons) that would be expected to be immunotoxic. Although the toxicological database is limited, Structurally related chemicals, including alkyl dimethyl benzyl amonium chloride like co mpounds (ADBACs) and Didecyl Dimethyl Ammonium Chloride like compounds (DDACs) have enough toxicology database indicating there is no immunotoxicity related signs in any of the existing studies. All studies indicating irritation is the primary concern for QACs like compounds. All studies indicating irritation is the primary concern for QACs like compounds.Page 33 of 37 

# Appendix B 

# Environmental Fate

Environmental Fate Properties

Environmental fate data reflecting testing of any t rimethoxysilyl QACs were used as surrogate for all other t rimethoxy silyl QACs because they are all expected to exhibit very similar behavior. The trimethoxysilyl QACs form stable polymers that are covalently bonded to the treated material and then degrade slowly to monomers (Green et al , 2011 and de Buyl )

. However, the rate of leaching from treated surfaces or materials is unknown. In water, any monomers will d egrade quickly to the quaternary amine portion (active and water soluble) and the other silyl portion (inactive and insoluble) with half

- lives of <1 hour (MRID 43811201 ). Sorption of the cationic portion of the molecule to soil and sediment will be the pri mary route of dissipation because soil and sediment are negatively

- charged and opposite electrical charges attract. The silyl portion of the molecule will become part of the soil and sediment matrices because of their high silica content. As a result, the only significant aquatic exposure is likely to be in the bottom sediment with minimal water column exposure.

As a result of this rapid hydrolysis , t he environmental exposure in surface water from WWTPs is based on the extent of sorption of the quaternary ammonium degradates to sludge. Three of the 4 compounds have estimated removal efficiencies of 82

- 90 % and one (PC Code 107409) has an estimated percent removal efficiency of 7.6 % (EPI

- Suite 4.1).
Trimethoxys ilyl QAC monomers will completely ionize in water at environmental pH values, and volatility and bioconcentration are expected to be minimal. A pKa is the pH in water where 50% of the compound is ionized and 50% is not ionized. The extent of ionization increases as the pH drops and decreases as the pH increases. Volatility from soil or water is not expected based on the vapor pressure and Henry’s Law Constants of 1.85 x 10 - 21 to 1.74 x 10 - 12 mm Hg and 1.1

x 10 - 25 to 1 x 10 - 16 atm • m 3 mol - 1 , respectively. Bioconcentration of the active portion will not be significant because of its removal in wastewater treatment plants by sludge sorption and the inactive portion will partition to sediment immediately.
Leaching from treated swimming pool and spa filters was not detected (LOD=49

- 60 ug/l). The treated media included sand, zeolite, and plastic fabric mesh (MRIDs 48851903, 47652806).Page 34 of 37 

# Appendix C 

# Ecotoxicology Profile

Toxicity to Terrestrial Receptors

Avian acute

- oral and dietary toxicity

There is one available avian acu te oral study with a mallard duck and four avian dietary studies testing two species the mallard and Northern bobwhite quail

. The available acute

- oral and dietary toxicity studies categorize the trimethoxysilyl QAC s as being practically nontoxic to birds ( Table 10 )

.
Table 10

– Avian Toxicity

Test Species Test Material ( % ai) Toxicity Toxicity Category Source

Mallard ( Anas platyrhynchos ) Trimethoxysilyl QAC s (42%) LC 50 >5620 ppm (diet) Practically nontoxic MRID 403852 17

LD 50 >159 0 mg ai/kg bw Not determined

– but no more than slightly toxic MRID 403852 18

LC 50 >5620 ppm (diet) Practically nontoxic MRID 403852 17 Northern bobwhite ( Colinus virginianus ) LC 50 > 5620 ppm (diet) Practically non toxic MRID 407701 06

LC 50 > 5620 ppm (diet) Practically non toxic MRID 403852 17

Mammals

T he t rimethoxysilyl QACs are practically nontoxic to small mammals (LD 50 >5000 mg ai/kg). No chronic effects have been reported (NOAEL >1000 mg ai/kg/day). See Appendix A for more information on all available mammalian toxicity studies.

Nontarget Insects

Nontarge t insect data are not required for the current use patterns. 

## Toxicity to Aquatic Receptors

Freshwater Fish

There are three available acute studies Appendix C categorize the t rimethoxysilyl QACs as being moderately toxic to freshwater fish (LC 50 s = 1.73 to 1.75 mg ai/L). Chronic data are not required because the t rimethoxysilyl QACs will quickly so rb to aquatic sediment which minimizes the potential for chronic exposure in the water column.Page 35 of 37 There are three available acute studies The available acute toxicity studies categorize the trimethoxysilyl QAC as being moderately toxic to freshwater fish ( Table 11 ). No chronic data are available.

Table 11

– Acute toxicity to freshwater fish

Test Species Test Material (% ai) Toxicity Endpoint (mg ai /L ) Toxicity Category Source (MRID)

Rainbow Trout ( Oncorhynchus mykiss) Trimethoxysilyl QAC s (42%) 96

- hr LC 50 = 1.73 Moderately toxic 410 01120

96

- hr LC 50 = 1.75 Moderately toxic 00105187

96

- hr LC 50 = 1.75 Moderately toxic 00105187

Freshwater Invertebrates

There are three available acute studies for the waterflea ( Table 12 ); these categorize the
t rimethoxysilyl QACs as being highly toxic to freshwater inv ertebrates (LC 50 s = 0.17 to 0.19 mg ai/L). No chronic data are available.

Table 12

– Acute toxicity to freshwater invertebrates

Test Species Test Material (% ai) Toxicity Endpoint (mg ai /L ) Toxicity Category Source (MRID)

Waterflea ( Daphnia
magna ) Trimethoxysilyl QAC s (42%) 48

- hr EC 50 = 0.18 High ly toxic 41001120

48

- hr EC 50 = 0.19 High ly toxic 00105187

96

- hr EC 50 = 0.17 High ly toxic 00105187

Estuarine/Marine Fish and Invertebrates

No acute or chronic data are available

. Aquatic Plants

No data are available

. Sediment Toxicity

No data are available.

Table 13

– Modeled toxicity data for alkyl quaternary ammonium surfactants

Endpoint Mono alkyl quaternary ammonium compounds 1 Di alkyl quaternary ammonium compound 1 1

- Decanaminium , N

- decyl

- methyl

- N

- [ 3

- (trimethoxysilyl) propyl ]

- , chloride 1,2
(C<16) (C 18) Avg 10 C chain Silanes (alkoxy) Neutral Organic SARPage 36 of 37 Acute freshwater fish (96

- h LC 50 ppm) 1.778 2.10 53.7 0.090* 0.032*

Acute daphnia (48

- h EC 50 ppm) 1.778 2.692 5.8 4.95* 0.029*

Acute mollusk (EC 50 ) -- 1.01

-- -- -- Green algae (96 hr EC 50 ) -- -- -- 0.976* 0.119*

Fish Chv 0.0019 0.005* Daphnia Chv 0.004* 0.009* Green algae Chv 0.998* 0.080*

* Chemical may not be soluble enough to measure this predicted effect. Chv (chronic value) from these models are equivalent to the maximum allowable toxicant concentration (MATC) which is equivalent to the geometric mean of the NOEC and LOEC. Since the NOEC is used in the agenc y’s pesticide risk assessment, these values will underestimate risk as compared to the use of an NOEC.

1 ECOSAR v 1.1 .1 surfactant special case

. 2 The more toxic of the four trimethoxysilyl QACs.Page 37 of 37 

# Appendix D 

# Comments Received Concerning the Preliminary Work Plan

The Agency received one comment on the initial dockets, described below. In the PWP, the Agency solicited comments on specific topics: environmental justice, water body impairment, trade irritants, and structure activity relationships. No comments or information were received during the public comment period concerning these issues.
Comment: The Physicians Committee for Responsible Medicine (PCRM) support s the use of exposure

- based waiving criteria as a general policy and specifically for the two toxicity studies in the Trimethoxysilyl QAC Preliminary Work Plan. If it is determined that the developmental toxicity and the reproductive toxicity studies cannot be waived then we suggest the registrant use OECD TG 443 Extended O ne

- Generation Reproductive Toxicity Study (EOGRTS) instead of the EPA guideline 870.3800 Two

- Generation Reproduction. This will allow the registrant to conduct one extended study saving many animals lives while addressing endpoints of interest. The TG is c urrently available on the OCED web site. Additionally, the developmental and reproductive toxicity studies can be combined to save even more animals, which EPA has stated is a priority in making risk assessment determinations.
Response: The Agency agrees t hat results from tests conducted according to OECD 443 11 or OCSPP Guideline 8 70.3800 can be submitted for consideration to address the Reproductive Toxicity Study requirement 12

.

11 http://www.oecd

- ilibrary.org/environment/test

- no

- 443

- extended

- one

- generation

- reproductive

- toxicity

study_9789264122550

- en 12 The Agency will accept a multi

- generation or an extended one

- generation reproductive and fertility effects study.