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 Data 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 Measures 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.............................................. 27
Page 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 Toxicology 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 Trimethoxysilyl 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 major 

degradates from outdoor uses. (A) Aquatic exposure routes. (B) Terrestrial exposure routes..... 23
Page 4 of 37

Human Health & Environmental Effects

William Hazel

Nathan Mottl

Jonathan Chen

Srinivas Gowda

Najm Shamim

William Erickson

James Breithaupt

Risk Management

Elizabeth Hernandez

Lance Wormell

Office of General Counsel

Philip Ross
Page 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 trimethoxysilyl

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 trimethoxysilyl QACs’ review.

Initially, this Registration Review was scheduled to address only 1-octadecanaminium-N, Ndimethyl-N-[3-(trihydroxysilyl) propyl] chloride (PC code 107403). However, because of their 

similar use patterns 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-decanaminium-N,N-didecyl-N-methyl-N-[3-(trimethoxysilyl)propyl] chloride (PC Code 

169160). The September 2007 RED (http://www.epa.gov/oppsrrd1/REDs/trimethoxysilyl-quatsred.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 QAC 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 trimethoxysilyl 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 trimethoxysilyl 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 

showing that they will not cause unreasonable risks to human health or the environment when 

used as directed on product labeling. The registration review program is intended to make sure 

that, as the ability to assess risk evolves and as policies and practices change, all registered 

pesticides continue to meet the statutory standard of no unreasonable adverse effects to human 

health or the environment. Changes in science, public policy, and pesticide use practices will 

occur over time. Through the registration review program, the agency periodically reevaluates 

pesticides to make sure that as change occurs, products in the marketplace can be used safely. 

Information on this program is provided at http://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 for 
Page 6 of 37

registration. The regulations governing registration 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 registration review decision. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the agency will develop and commit to a Final Work Plan (FWP) and 

anticipated schedule for the Trimethoxysilyl QAC Case. The Trimethoxysilyl Quaternary 

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-2013-0095, EPA-HQ-OPP-2013-0096 and EPA-HQ-OPP-2013 -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 (see 3.2.2) N/A New

Two-generation reproductive toxicity1

Developmental toxicity1

Occupational Handler Yes 2007 RED New Occupational exposure data 

Inhalation toxicity study 

Residential Handler Yes 2007 RED Updated Indoor exposure data 

Inhalation toxicity study 

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 study

Cumulative No (see 3.4) N/A No 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 Date2 Completion Date

Phase 1: Opening the Docket 

Open Docket and 60-Day Comment Period for Preliminary 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 2013-09-12

Issue Data Call-In (DCI) 2014-09

Receive Data to be Considered in Risk Assessment 2016-09

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 Proposed 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 Quaternary Ammonium 

Chloride pesticide products.

• Updated Table 6 to clarify those results from tests conducted according to OECD 4433 or 

OCSPP Guideline 870.3800 can be submitted for consideration to address the 

Reproductive Toxicity Study requirement. This update was made in response to the 

comment received during the public comment period (see Appendix D ).

• Corrected formatting and typographical errors

The Agency received one comment on the initial docket. The comment received did not affect 

the data needs, work plan and timeline 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 testing. 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-octadecanaminium-N, Ndimethyl-N-[3-(trihydroxysilyl) propyl] chloride (PC code 107403). However, because of their 

 2 The anticipated schedule will be revised 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_9789264122550-

en
Page 8 of 37

similar use patterns 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-decanaminium-N,N-didecyl-N-methyl-N-[3-(trimethoxysilyl)propyl] chloride (PC Code 

169160). The September 2007 RED (http://www.epa.gov/oppsrrd1/REDs/trimethoxysilyl-quatsred.pdf ) addressed these simultaneously because of the similarities described above. According 

to the 2011-2014 public Registration Review schedule, case 3148 and 5113 were planned to 

begin in fiscal year 2015. To ensure the public is able to locate information associated 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 trimethoxysilyl quaternary ammonium chlorides

(trimethoxysilyl QACs). As a result of this grouping and merger, the trimethoxysilyl QACs case

will now include:

1. Case 3148: 1-Octadecanaminium-N, N-dimethyl-N-(3-(trimethoxysilyl) propyl) 

chloride (PC code 107401) and 1-Decanaminium-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 dockets for the trimethoxysilyl QAC (Case 3148, Case 5100, Case 5113) has been 

established at http://www.regulations.gov in docket number EPA-HQ-OPP-2013-0095; EPAHQ-OPP-2013-0096; EPA-HQ-OPP-2013 -0085.

1.4 Chemical Identification and Properties

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

Octadecanaminium- N, N-dimethyl-N-[3-(trimethoxysilyl) propyl] chloride (PC Code: 107401),

1-Octadecanaminium-N,N-dimethyl-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 these cases will be referred to collectively as “trimethoxysilyl QACs”.
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, Ndecyl-N-methyl-N-[3-

(trimethoxysilyl]

propyl)-, chloride

1-Octadecanaminium-N, 

N-dimethyl-N-[3-

(trihydroxysilyl) propyl]-

chloride

Common 

Name

3-(trimethoxysilyl) 

propyl dimethyl 

octadecyl ammonium 

chloride

Dimethyltetradecyl [3-

(trimethoxysilyl) propyl] 

ammonium chloride

N,N-Didecyl-N-methyl3-(trimethoxysilyl) 

propanaminium chloride

3-(trihydroxysilyl) propyl 

dimethyl octadecyl 

ammonium chloride

Classification 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 C26H58ClNO3Si C22H50ClNO3Si C27H60ClNO3Si C23H52ClNO3Si

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 Trimethoxysilyl Quaternary Ammonium Chloride Compounds

107401

1-Octadecanaminium, N,N-dimethyl-N-[3(trimethoxysilyl)propyl]-, chloride

107403

1-octadecananminium-N,N-dimethyl-N-[3-(trihydroxysilyl)propyl]-, chloride
Page 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 trimethoxysilyl QACs 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-Nmethyl-3-

(trimethoxysilyl) 

propanaminium 

chloride

1-ocatdecanaminiumN,N-dimethyl-N-[3-

(trihydroxysilyl) 

propyl]-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 amber Clear

830.6303

Physical State Liquid Liquid Liquid Liquid

830.6304

Odor

Characteristic

Silane odor

Characteristic

Silane odor

Characteristic

Silane odor

Characteristic

Silane odor
Page 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-Nmethyl-3-

(trimethoxysilyl) 

propanaminium 

chloride

1-ocatdecanaminiumN,N-dimethyl-N-[3-

(trihydroxysilyl) 

propyl]-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 will 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 (noctanol/ water)

Log Kow

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 39 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 concentrate 
Page 12 of 37

and ready to use solution. There are 17 products containing 1-Octadecanaminium, N,N-dimethylN-[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 trimethoxysilyl QACs that will be assessed 

in this registration review. Trimethoxysilyl QAC products can be applied using the following 

application 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 brush/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.

Fogger, pressure sprayer, pump-up sprayer, 

carpet steam cleaner, dip treatment, brush, 

foaming apparatus, pad, trigger spray 

bottle

1,000-10,000 ppm

Surface treatment of outdoor building 

materials including roofing and exterior walls 

made of wood, stone, brick, metal, tile, etc.

Pressure 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.

Pressure 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

Pressure sprayer, pump-up sprayer, dip 

treatment, pad, brush, foaming apparatus 1,000-10,000 ppm

Air filters and materials, nonfood conveyor 

belts

Pressure sprayer, pump-up sprayer, dip 

treatment, pad, brush, foaming apparatus 1,000-10,000 ppm

Commercial and residential paints Brush/roller and airless sprayer 1,000-10,000 ppm
Page 13 of 37

1.5.3 Usage Information 

Usage information is not available for the trimethoxysilyl QACs. The Kline Biocides Report for 

2004/2005 (Kline, 2005) does not include the trimethoxysilyl QACs.

1.6 Regulatory History

The trimethoxysilyl QACs are registered as bacteriostatic, algistatic, and fungistatic compounds. 

The first products containing1-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 containing 1-Octadecanaminium-N, N-dimethyl-N-[3-

(trihydroxysilyl) propyl]-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 tolerance 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 Human Health 

No trimethoxysilyl QAC human poisoning incidents have been reported in OPP’s Incident Data

System (IDS) from 1992 to the present.

1.7.2 Ecological

No trimethoxysilyl QAC ecological incidents have been reported in OPP’s Incident Data System 

(IDS) from 1992 to the present.

2 Anticipated Data Needs
Page 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-2013-0096; EPA-HQ-OPP-2013 -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 

Study1

Special leaching study 

from roofing shingles 

and fascia board 

TGAI2 12 Environmental fate Exterior surfaces (e.g., Treated 

shingles, walls, and fascia board)

Transport to the aquatic 

environment

835.12303

Leaching-adsorptiondesorption (batch 

equilibrium)

TGAI2 12 Environmental Fate Exterior surfaces (e.g., Treated 

shingles, walls, and fascia board)

Transport to the aquatic 

environment

835.41003 Aerobic soil 

metabolism TGAI2 12 Environmental Fate Exterior surfaces (e.g., Treated shingles, walls, and fascia board)

Transport to the aquatic 

environment

835.44004 Anaerobic aquatic 

metabolism TGAI2 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 

amphipod5

and a 

chironomid5)

TGAI6 12 Ecological Exterior surfaces (e.g., Treated 

shingles, walls, and fascia board)

Transport to the aquatic 

environment

Special 

study

Whole sediment 

chronic toxicity, 

marine invertebrate 

(an amphipod7)

TGAI6 12 Ecological Exterior surfaces (e.g., Treated 

shingles, walls, and fascia board)

Transport to the aquatic 

environment

850.4400

850.4550

Aquatic plant toxicity

(non-vascular) 4 

species: green algae, 

freshwater diatom8

, 

saltwater diatom8

, and 

a cyanobacteria8

TGAI6 12 Ecological Exterior surfaces (e.g., Treated 

shingles, walls, and fascia board)

Transport to the aquatic

environment

850.4500 Aquatic plant toxicity 

(vascular) TGAI6 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 involving

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

870.3700b9 Developmental 

Toxicity in Rabbits TGAI 24 Dietary (drinking water) Exterior surfaces (e.g., Treated shingles and fascia board)

Dietary exposures from drinking 

water.

870.38009, 

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 uses10

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 anticipated 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 quaternary ammonium degradate. 3 Leached residues in treated shingles and 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 environmental exposure, then anticipated data needs 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 metabolism 

(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 silyl compounds by hydrolysis. Documentation of stable 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 plumulosus 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 IC50 and 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 data 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 be submitted for 

consideration in response to this requirement.
Docket Numbers EPA-HQ-OPP-2013-0095; EPA-HQ-OPP-2013-0096; EPA-HQ-OPP-2013 -

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 trimethoxysilyl 

QACs. 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 toxicological endpoints of concern for trimethoxysilyl QACs. 

The studies anticipated as being required through this registration review will allow the agency 

to establish the endpoints necessary to conduct risk assessment.

3.2 Dietary Exposure 

3.2.1 Food 

Human dietary 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 endpoints 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 trimethoxysilyl QACs

in food are not expected to be conducted.

3.2.2 Drinking Water

EPA anticipates revisiting the need to conduct a drinking water assessment based on the results 

of the environmental fate and toxicity studies anticipated as 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 QACs to leach into 

water from treated materials and surfaces, there may be human exposure via drinking water. 

Treated materials and surfaces must 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 Appendix 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. No 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 the 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 trimethoxysilyl 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 trimethoxysilyl QACs 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, occupational and residential risk assessments were not conducted to support the 

RED. Dermal risk assessments 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 toxicity 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 review, 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 toxicity studies 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 risks to handlers due to the lack of an inhalation 

toxicity study as well as inhalation exposure studies reflecting 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. Paint 

application using an airless sprayer and paint brush/roller would also generate aerosols. The 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 their labels prior to risk assessment, the 

agency intends to assess 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 pressures of the 

trimethoxysilyl QACs 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 an oral developmental toxicity study at a limit dose 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 trimethoxysilyl QAC exposure scenarios that 

will need to be assessed for registration review is included 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 

paint 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 studies 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 aggregated.

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 toxicity 

finding as to the trimethoxysilyl QACs and any other substances and the trimethoxysilyl QACs

do not appear to produce a toxic metabolite produced by other substances. For the purposes of 
Page 21 of 37

this registration review, therefore, EPA has not assumed that the trimethoxysilyl QACs have 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 policy 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 an environmental risk assessment that supports a complete 

endangered species determination for the trimethoxysilyl QACs. Outdoor applications of the 

trimethoxysilyl QAC to exterior walls, sidewalks, roofing and siding may result in movement of the 

ai into the aquatic environment 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 registration review will allow 

the agency to determine whether the use of these trimethoxysilyl 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 designated critical habitat, the agency will consult with the U.S. Fish and Wildlife Service 

and/or National Marine Fisheries Services (the Services), as appropriate.

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 trimethoxysilyl QACs and their degradates. Figure 1 contains the conceptual model for the 

environmental exposure from the indoor uses as a sanitizer and disinfectant, and uses as a 

material preservative in textiles and plastic/rubber manufacturing process. Figure 2 contains the 

conceptual models for the outdoor/exterior uses on 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 are 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 roofing 

materials, which can result in leaching and runoff across lawns, 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 uses 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 quaternary 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

Sediment
Page 23 of 37

Figure 2 - Conceptual model for environmental exposure to trimethoxysilyl QACs and its 

major degradates from outdoor uses. (A) Aquatic exposure routes. (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 risk
Page 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 trimethoxysilyl QAC to plants and 

animals. Relevant data from the open literature available in ECOTOX also may be used to 

evaluate potential direct and indirect effects.

4.2.1 Mode of Action

Like other quaternary ammonium compounds trimethoxysilyl QAC compounds are membraneactive agents, causing leakage of intracellular molecules leading to death. 

4.2.2 Measures of Effect (Ecotoxicity 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 not currently available.

Table 8 - Selected Endpoints and Data Gaps for Risk Assessment of Trimethoxysilyl QACs

Receptor Group Test Material Surrogate Species Risk Scenario Toxicity Endpoint Source

Freshwater fish TGAI1 Rainbow trout

Acute 96-h LC50 = 1.73 mg ai/L MRID 41001120

Chronic Data waived2 NA

Freshwater 

invertebrates TGAI1 Waterflea

Acute 48-h EC50 = 0.17 mg/L MRID 00105187

Chronic Data required NA

Estuarine/marine 

fish TGAI1 Fish

Acute Data waived3 NA

Chronic Data waived3 NA

Estuarine/marine 

invertebrates TGAI1 Shrimp (mysid)

Acute Data required NA

Chronic Data waived4 NA

Mollusk Acute Data required NA

Benthic 

invertebrates TGAI1

Freshwater (1 

chironomid sp. and 1 

amphipod sp.)

Chronic Data required NA

Estuarine/marine (1 

amphipod sp.) Chronic Data required NA

Aquatic plants

(nonvascular) TGAI1 4 species4 IC50 and 

NOAEC

Data required for 4 species 5 NA

Aquatic plants

(vascular) TGAI1 Duckweed IC50 and 

NOAEC Data required NA

Birds TGAI Mallard Acute LD50 > 1590 mg ai/kg-bw MRID 40385218
Page 25 of 37

Receptor Group Test Material Surrogate Species Risk Scenario Toxicity Endpoint Source

Dietary LC50 >5620 ppm ai MRID 40385217

Chronic Data not required NA

Mammals TGAI Lab. rat 

or mouse

Acute LD50 >5000 mg ai/kg-bw MRID 40385201

Chronic NOAEL >1000 mg ai/kgbw/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 risks 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 alkyl 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 anticipated to be required. If 

the green algae study demonstrates detrimental effects do not 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 additional 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 

compounds can be used (e.g., DDAC4 and DDACB5

).

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 comparable to 

freshwater species (e.g., DDAC3 and DDACB4). 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., DDAC3 and DDACB4

) 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 anticipated to be needed to 

assess risk.

 4 Didecyl dimethyl ammonium chloride, Case 3003, EPA docket EPA-HQ-OPP-2006-0338 5 Didecyl dimethyl ammonium carbonate and bicarbonate Case 5014, EPA-HQ-OPP-2012-0651
Page 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. If 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 diatom, 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 

benthic 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. According 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 

guideline7 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 (quaternary 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 with 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 trimethoxysilyl QACs 

from applications to roofing and siding and for down-the-drain estimates for uses that discharge 

into waste water treatment 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 drinking water because the 

trimethoxysilyl QACs form polymers 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 potential for human 

exposure to the trimethoxysilyl QACs via drinking water, leaching studies are anticipated to be

required. Whether reproductive and developmental toxicity studies are 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 Analysis

No screening Down-the-Drain analysis was conducted because releases of trimethoxysilyl 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, hydrolytically, 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 

alkyl quaternary ammonium which will sorb to solids. The next step would be rapid degradation 

of alkyl groups (C10 to C14) on the alkyl quaternary ammonium degradate and mineralization.

Because of the inherent instability of the parent Trimethoxysilyl QACs and sorption (Appendix 

B ) and biodegradation of the alkyl quaternary ammonium degradates, insignificant or no 

exposure to the parent or its toxic degradates will result from the down-the-drain exposure 

pathway. 

4.4 Effects Analysis Plan

In addition to the required 850 OCSPP guideline studies, open literature studies will be identified 

through EPA’s ECOTOXicology (ECOTOX) database9

. This database employs a literature 

search engine for locating chemical toxicity data for aquatic 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 QACs is prepared. At 

that time, endpoints more sensitive than what is currently known will be reviewed from the open 

literature studies. Data from the ECOTOX run for the trimethoxysilyl 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 potential 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 the 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 trimethoxysilyl QACs, EPA reviewed these 

data and selected the most sensitive endpoints for relevant risk assessment scenarios from the 

existing hazard database. However, as required by FFDCA section 408(p), trimethoxysilyl QAC

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

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by 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 ingredients and 9 inert ingredients. Trimethoxysilyl 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 callins, requiring the submission of EDSP screening assays for Trimethoxysilyl 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 2014. The Agency 

will conduct human health and environmental 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/publications/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 

Project 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 

Research and Technological Advances, A. Mendez-Vilas (Ed). 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC380687/pdf/applmicro00052-0033.pdf
Page 30 of 37

Appendix A Toxicology Profile

Acute Toxicity for Product Labeling 

As listed in Table 9, acute toxicity data for a 50% formulation of 3-(trimethoxysilyl) propyl 

dimethyl octadecyl ammonium chloride show low acute toxicity for single exposures by the oral, 

dermal, and inhalation routes (Categories IV, III, and IV 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 LD50 > 5000 mg/kg IV

870.1200

(81-2) 40385201 Dermal LD50 > 2000 mg/kg III

870.1300

(81-3)

Not 

Available

Inhalation LC50 > 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 subchronic 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 LC50 exceeded the limit dose for acute inhalation toxicity
Page 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 deaths 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 corn oil) was administered by gavage to pregnant 

Sprague-Dawley rats (25/sex/dose) on days 6 through 15 of gestation at 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, and the Maternal LOAEL is >1000 mg/kg/day. The developmental toxicity 

NOAEL is considered to be ≥1000 mg/kg/day, and the developmental 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.

This rat study was the only developmental toxicity study available for the trimethoxysilyl QACs. 

Although no evidence of increased susceptibility of offspring was observed following in utero 

exposure up to and including a limit dose (1000 mg/kg/day), an additional developmental study 

in another species is anticipated to be needed to characterize the hazard of the trimethoxysilyl 

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. However, 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 reproductive toxicity 

study is anticipated to be needed 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 trimethoxysilyl QACs.

Carcinogenicity 

There is no carcinogenicity study available, but none is needed. There are no concerns for 

carcinogenicity for the trimethoxysilyl QACs 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 carcinogenicity study is required.

Mutagenicity 

The mutagenicity of the trimethoxysilyl QACs 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 trimethoxysilyl QACs are negative for mutagenicity

Immunotoxicity

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 chemicals (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 compounds (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 trimethoxysilyl QACs were used as surrogate 

for all other trimethoxysilyl 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 

degrade 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 primary 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, the 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). 

Trimethoxysilyl 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•m3 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 acute 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 QACs as being practically nontoxic to birds (Table 

10).

Table 10 – Avian Toxicity

Test Species Test Material

(% ai) Toxicity ToxicityCategory Source

Mallard 

(Anas platyrhynchos)

Trimethoxysilyl 

QACs

(42%)

LC50 >5620 ppm (diet) Practically nontoxic MRID 

40385217

LD50 >1590 mg ai/kg bw

Not determined – but 

no more than slightly 

toxic

MRID 

40385218

LC50 >5620 ppm (diet) Practically nontoxic MRID 

40385217

Northern bobwhite

(Colinus virginianus) LC50 > 5620 ppm (diet) Practically nontoxic MRID 40770106

LC50 > 5620 ppm (diet) Practically nontoxic MRID 

40385217

Mammals

The trimethoxysilyl QACs are practically nontoxic to small mammals (LD50 >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

Nontarget 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 trimethoxysilyl QACs as 

being moderately toxic to freshwater fish (LC50s = 1.73 to 1.75 mg ai/L). Chronic data are not 

required because the trimethoxysilyl QACs will quickly sorb 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 QACs

(42%)

96-hr LC50 = 1.73 Moderately toxic 41001120

96-hr LC50 = 1.75 Moderately toxic 00105187

96-hr LC50 = 1.75 Moderately toxic 00105187

Freshwater Invertebrates 

There are three available acute studies for the waterflea (Table 12); these categorize the 

trimethoxysilyl QACs as being highly toxic to freshwater invertebrates (LC50s = 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 

QACs

(42%)

48-hr EC50 = 0.18 Highly toxic 41001120

48-hr EC50 = 0.19 Highly toxic 00105187

96-hr EC50 = 0.17 Highly 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 compounds1

Di alkyl quaternary 

ammonium 

compound1

1-Decanaminium, N-decyl-methyl-N-[3-

(trimethoxysilyl) propyl]-, chloride1,2

(C<16) (C 18) Avg 10 C chain Silanes (alkoxy) Neutral Organic SAR
Page 36 of 37

Acute freshwater 

fish (96-h LC50

ppm)

1.778 2.10 53.7 0.090* 0.032*

Acute daphnia (48-

h EC50 ppm) 1.778 2.692 5.8 4.95* 0.029*

Acute mollusk 

(EC50) -- 1.01 -- -- --

Green algae (96 hr 

EC50) -- -- -- 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 agency’s pesticide risk assessment, 

these values will underestimate risk as compared to the use of an NOEC.

1 ECOSAR v1.1.1 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) supports 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 One-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 currently 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 that results from tests conducted according to OECD 44311

or 

OCSPP Guideline 870.3800 can be submitted for consideration to address the Reproductive 

Toxicity Study requirement12. 

 11 http://www.oecd-ilibrary.org/environment/test-no-443-extended-one-generation-reproductive-toxicitystudy_9789264122550-en 12 The Agency will accept a multi-generation or an extended one-generation reproductive and fertility effects study.