### Docket Number: EPA

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Page 2 of 130 Triclosan Registration Review Team

Human Health William Hazel (now retired) Timothy Leighton Tim McMahon

Environmental Fate and Effects James Breithaupt Srinivas Gowda Pat Jennings William Erickson Najm Shamim Donna Randall

Risk Management Sandra O’Neill Rose Kyprianou

Office of General Counsel Philip Ross Andrea Medici

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## Contents

List of Tables

................................ ................................ ................................ ................................ .. 4 List of Figures

................................ ................................ ................................ ................................ . 5

1 Introduction

................................ ................................ ................................ ............................. 6

1.1 Statutory and Regulatory Authority

................................ ................................ ................. 6

1.2 Updates to the Work Plan

................................ ................................ ................................ . 7

1.3 Case Overview

................................ ................................ ................................ ............... 10

1.4 Chemical Identification and Properties

................................ ................................ .......... 10

1.5 Use/Usage Description

................................ ................................ ................................ ... 12

1.5.1 Summary of Registered Uses

................................ ................................ .................. 12

1.5.2 Usage Information

................................ ................................ ................................ .. 14

1.6 Regulatory History

................................ ................................ ................................ ......... 15

1.6.1 Rece nt/Pending Regulatory Actions

................................ ................................ ....... 16

1.6.2 Tolerance Information

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

1.7 Incidents

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

1.7.1 Human Health

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

1.7.2 Ecologic al

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

2 Anticipated Data Needs

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

3 Human Health Risk Assessment

................................ ................................ ........................... 24

3. 1 Existing Toxicological Endpoints

................................ ................................ .................. 24

3.2 Dietary Exposure

................................ ................................ ................................ ............ 26

3.3 Occupational and Residential Exposures

................................ ................................ ....... 26

3.3.1 Occupational Handler Exposures

................................ ................................ ............ 27

3.3.2 Residential Handler Exposures

................................ ................................ ............... 27

3.3.3 Residential Post

- Application Exposures

................................ ................................ . 27

3.4 Aggregate and Cumulative Exposure

................................ ................................ ............. 28

3.4.1 Aggregate Exposures

................................ ................................ .............................. 28

3.4.2 Cumulative Exposures

................................ ................................ ............................ 28

4 Environmental Risk Assessment

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

4.1 Environmental Conceptual Model Exposure Pathways

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

4.2 Ecological Effects Assessment

................................ ................................ ....................... 31

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Page 4 of 130 4.2.1 Mechanism of Action

................................ ................................ .............................. 31

4.2.2 Measures of Effect (Ecotoxicology Endpoints)

................................ ...................... 32

4.3 Exposure Analysis Plan

................................ ................................ ................................ .. 33

4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates

................................ ............ 33

4.3.2 Textile Manufacturing Monitoring Data

................................ ................................ . 34

4.3.3 Water Quality

................................ ................................ ................................ .......... 36

4.3.4 Screen ing

- Level of Potential Risks to Aquatic Organisms from Pesticidal Uses of Triclosan Potentially Released to Wastewater Treatment Plants (WWTPs)

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

4.4 Effects Analysis Plan

................................ ................................ ................................ ..... 38

5 Endocrine Disruptor Screening Program (EDSP)

................................ ................................ . 38

6 Next Steps

................................ ................................ ................................ ............................. 39

7 References

................................ ................................ ................................ ............................. 39 APPENDIX A: Toxicology Profile

................................ ................................ .............................. 41

APPENDIX B: Environmental Fate

................................ ................................ ............................. 60

AP PENDIX C: Ecotoxicity Profile

................................ ................................ ............................... 81 APPENDIX D: Environmental Fate and Ecotoxicity Data for Appendices B and C

................. 104

APPENDIX E: Web

- ICE and ECOSAR Results

................................ ................................ ........ 119 APPENDIX F: For Ecological Assessment

- Dioxins of Concern and Equivalency Factors

..... 129



## List of Tables

Table 1

- Summary of Anticipated Risk Assessments and Data Needs for Registration Review of Triclosan

................................ ................................ ................................ ............................. 9 Table 2

- Anticipated Registration Review Schedule

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

- Chemical Identification of Triclosan

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

- Physical

- Chemical Properties for Triclosan

................................ ................................ .. 11 Table 5

- Triclosan Antimicrobial Use Summary

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

– Studies Anticipated as Needed for Registration Review of Triclosan

.......................... 21 Table 7

– Data Needs Required by the October 5, 2011 Data Call

- In for the Triclosan RED

...... 22 Table 8

- Toxicological Endpoints Used for the Triclosan RED

................................ .................. 24 Table 9

- Occupational Handler Exposure Scenarios for Triclosan

................................ ............. 27 Table 10

- Effects Endpoints for the Ecological Risk Assessment of Triclosan

.......................... 32 Table 11

— Textile Facility Characteristics During the Triclosan Monitoring Studies

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

— Triclosan and Methyl Triclosan Monitoring Data from Two Textile Manufacturing Facilities

................................ ................................ ................................ ............................ 36

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Page 5 of 130 Table 13

- Acute Toxicity Profile for Triclosan

................................ ................................ ........... 41 Table 14

- Non

- Acute Toxicity Studies for Triclosan

................................ ................................ .. 42 Table 15

- Abiotic Degradation of Triclosan and Degradate Formation

................................ ...... 63 Table 16

- Metabolism of Triclosan with Formation of Degradates

................................ ............ 66 Table 17

- Effect of pH on the Ionization of Triclosan at 20 o 

### C

................................ ................... 68 Table 18

- Leaching and Adsorption

- Desorption of Triclosan to Soil and Sediment

.................. 69 Table 19

- Terrestri al Field Dissipation, Surface Runoff, Leaching, and Crop Uptake

............... 70 Table 20

- Environmental Monitoring Studies for Triclosan

................................ ....................... 73 Table 21

– Biological Field Monitoring of Aquatic Organisms

................................ ................... 77 Table 22 WWTP Studies for Triclosan

................................ ................................ ......................... 79 Table 23

- Textile Monitoring Facility Characteristics

................................ ................................ . 80 Table 24

- Textile Triclosan and Methyl Triclosan Monitoring Concentrations

.......................... 80 Table 25

- Toxicity of Triclos an to Birds

................................ ................................ ..................... 81 Table 26

- Acute Toxicity of Triclosan to Aquatic Animals from Submitted Studies and Reviewed Open Literature

................................ ................................ ................................ 86 Table 27

- Acute Toxicity of Triclosan to Aquatic Animals from Open Literature Provided by OW

................................ ................................ ................................ ................................ .... 89 Table 28

- Chronic Toxicity of Triclosan to Aquatic Animals from Submitted Studies and Reviewed Open Literature

................................ ................................ ................................ 91 Table 29

- Chronic Toxicity of Triclosan to Aquatic Animals from Open Literature Provided by OW

................................ ................................ ................................ ................................ .... 93 Table 30

- Toxicity of Triclosan to Sediment Benthos from Submitted Studies

.......................... 94 Table 31

- Toxicity of Triclosan to Aquatic Plants from Submitted Studies

................................ 95 Table 32

- Toxicity of Triclosan to Aquatic Plants from Open Literature Reviewed by OW

...... 96 Table 33

- Other Chronic Data on the Effects of Triclosan on Aquatic Organisms from Open Literature Reviewed by OW

................................ ................................ ............................. 98 Table 34

- Acute Toxicity of Methyl Triclosan to Aquatic Organisms from Open Literature Provided by OW

................................ ................................ ................................ ............. 102 Table 35

- Dioxin Congeners of Toxic ological Concern; Toxicity equivalency factors for mammals, birds and fish associated with each isomer are from U.S. EPA 2008b

......... 129



## List of Figures

Figure 1

- Conceptual Model for Environmental Exposure from Treatment of Textiles with Triclosan

................................ ................................ ................................ ........................... 30 Figure 2

- Conceptual Model for Environmental Exposure from In

- Service Use of Triclosan in Plastic Agricultural Film and Mulch

................................ ................................ ................. 31

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## 1 Introduction

This document is the Environmental Protection Agency’s (EPA or “the a gency”) Final Work Plan ( F WP) for triclosan. The F WP document explains what EPA's Office of Pesticide Programs knows about triclosan, highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the a gency in conducting the review, and providi ng an anticipated timeline for completing triclosan’s review.

The memo randum titled “Triclosan Response to Comments Memo” addresses public comments received during the comment period concerning the Preliminary Work Plan (PWP), which is posted in the triclo san registration review docket (EPA

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- 0 811 ). The memo is also posted in the triclosan registration review docket. T his document makes final the work plan for the triclosan registration review process.



### 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 A gency (USEPA, EPA, or the a gency) 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 regi stration review program, the a gency 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 a gency 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 registration. The regulations governing registration review begin at 40 CFR 155.40. The a gency will consider benefits inform ation 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

a gency’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. The Triclosan 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 www.regulations.gov in docket EPA

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

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### 1.2 Updates to the Work Plan Since the publication of the PWP, comments received resulted in a modification to the anticipated data needs identified in the Triclosan PWP. The anticipated data needs in the Triclosan PWP were modified for the following reasons: (1) open literature reviews were completed for some biotic metabolism fate studies r esulting in removal of those anticipated data requirements; (2) waivers were submitted for two anticipated fate data requirements and were accepted as meeting data requirements for those anticipated data needs ; and (3) the 850.3300 (or OECD 209) Activated Sludge, Inhibition Respiration (ASRI) study was added as an anticipated data requirement to support registration review of the textile/fabric use pattern

.

T he agency has made the following updates , divided into two categories, 1.) updates made as a result of the comments received concerning the PWP, and 2.) other updates :

Updates made a s a result of the comments received to the triclosan PWP:

• Added the 850.3300 (or OECD 209) ASRI as an anticipated data requirement to support registration review of the textile/fabric use pattern.

• Clarified that EPA’s aggregate assessment to account for exposure to triclosan for children under 6 years old will include the most up

- to

- date information provided the information complies with EPA’s Rule on Protections for Subj ects in Human Research Involving Pesticides (Section 3.4).

• Updated characterization of the ecotoxicity data that were available at the time of the 2008 RED in Section 4.

• Added discussion about triclosan degradates to Section 4.3 Exposure Analysis Plan.

• Clarified the reasons that

, in the case of pesticidal material preservative uses of triclosan, the environmental exposure pathway consisting of leaching of triclosan from in

- service use of these materials with subsequent releases to wastewater was identifi ed as a low likelihood of contributing to environmental risks of concern.

• Defined the term “PCE” under the figures in the Environmental Conceptual Model Exposure Pathways , Section 4.1.

• Change d Table 7 and 10 and the Benthic Invertebrate subsection of Appen dix C to clarify that chronic, spiked

- sediment benthic invertebrate testing for two freshwater and one estuarine/marine species is already required under the post

- RED DCI ( issued on October 5, 2011 ) which is why they are not identified in Table 6 as additi onal anticipated data requirements for registration review.

• Corrected errors and missing data in the Web

- ICE and ECOSAR Appendix E, and the resulting correction of the acute mysid value in the Ecotoxicity Profile Appendix C.

• Modified Section 4 Tables 11, 1 2, 23 and 24; and Appendices C, E, and D based on technical corrections of the textile effluent monitoring data, comment numbers 48

- 54 in the “Triclosan Response to Comments Memo

. ”

Other Updates :

• C orrect ion of the anticipated registration review schedule (Table 2)

.

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Page 8 of 130 • Deleted data requirements no longer anticipated to be required to support registration review since these are to be addressed in the submission of the remaining anticipated exposure data requirements:

o 875.1600: Data Reporting and Calculations ;

o 875.2900: Data Reporting and Calculations

.

• Added S ection 4.3.4 on the screening level down the drain analysis for in service use of materials preserved with triclosan.

• Clarified in the Exposure Analysis Plan that additional open literature regarding fate would be identified and included.

• Updated Section 5 EDSP language to reflect that a second list of chemicals was identified for EDSP screening

.

• The results of the water quality portion of S ection 6.1.2 from the PWP were moved into S ection 4. 3

. 3 of this FWP

.

• Updated text and tables in Appendix B Environmental Fate to address completed review of waiver requests and the following open literature studies: Ying et al. (2007); Xu et al. (2009); Carr et al. (2011); Ying et al. (2011).

• Added a s ection on wastewater treatment studies in Appendix B, and moved wastewater studies out of the existing biotic fate tables to a separate table addressing wastewater treatment studies specifically , this is now Table 22

.

• Updated tables in Appendix B Environmental Fate to include information on temperature, % purity and source information where it was missing, and moved incorrectly placed studies to the correct table.

• Split the references for citations in the Ecotoxicity Profile Appendix C into a separate Appendix D and added refe rences for citations in the Environmental Fate Assessment Appendix B into the new Appendix D.

The a gency received over 150 individual comment s from 1 1 organizations and one private citizen concerning the materials included in the initial docket. Most comm ents were received from clean water agencies and clean water advisory boards voicing concerns about the EPA’s approach to risk assessments for triclosan. These clean water organizations also made suggestions for refinements. These commenter s were the Bay A rea Clean Water Agencies (BACWA), the Central Valley Regional Water Quality Control Board, the San Francisco Bay Regional Water Quality Control Board, the California Stormwater Quality Association (CASQA), the Hampton Roads Sanitation District (HRSD), the National Association of Clean Water Agencies (NACWA), and Tri

- Tac.

Vivimed Labs

- a triclosan manufacturer, the Colgate Palmolive Company, and several other interested stakeholders also provided comments during the public comments period.
A summary of th e comments received and the a gency’s responses are presented in the Triclosan Response to Comments Memo, which can be viewed at www.regulations.gov in docket EPA

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.

Tables 1

- 2 b elow summar ize the issues relevant to this registration review case and the anticipated registration review schedule

.

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Page 9 of 130 Table 1

- Summary of Anticipated Risk Assessments and Data Needs for Registration Review of Triclosan

Risk Assessment Assessme nt Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed

Dietary (food) Yes 1 2008 Updated None Dietary (drinking water) Yes 1 2008 Updated None

Occupational Handler Yes 2008 Updated Dermal and inhalation exposure scenarios

Residential Handler No (see 3.3) 2008 None None

Residental Post

Application

– Incidental Oral and Dermal Yes 1 2008 Updated None

Residential Post

Application

– Inhalation No (see 3.3) N/A None None

Aggregate Yes 1 2008 Updated None

Cumulative No (see 3.4.2) N/A None None

Tolerance Review Yes (see 1.5.3) N/A None None

Ecological Yes 2008 Updated Acute mysid shrimp and mollusk; daphnid, m ysid and fish life cycle tests; l eaching from agricultural film and mulch

, 2 activated sludge respiration inhibition

*Table 1 is a summary of the anticipated risk assessments and data needs for Registration Review. For data called in through the post

RED DCI, see Table 7.

1 Dietary (food and drinking water) and residential exposure are part of the general population biological monitoring data from NHANES and will be accounted for in the anticipated aggregate assessment.

2 EPA has received a request to terminate the use of triclosan in agricultural film s and mulches. If the cancellation order becomes effective and all product labels are amended to remove the use, this anticipated data should no longer be needed.



### Table 2

- Anticipated Registration Review Schedule

Anticipated Activity Target Date 1 Completion Date
Phase 1: Opening the Docket Open Docket and 60

- Day Public Comment Period for Preliminary Work Plan 201 3

- 03 2013

- 03

- 2 7

Close Public Comment Period 201 3

- 05 2013

- 05

- 28
Phase 2: Case Development

Issue Final Work Plan 201 4

- 0 3 201 4

- 0 4

Issue Data Call

- In (DCI) 201 5

- 0 3
Receive Data to be Considered in Risk Assessment 201 7

- 0 3

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Page 10 of 130 Open 30

- Day Public Comment Period for Preliminary Risk Assessment 201 8

- 0 9

Close Public Comment Period 201 8

- 10
Phase 3: Registration Review Decision and Implementation Open 60

- Day Public Comment Period for Proposed Decision 20 19

- 0 3
Close Public Comment Period 20 19

- 05

Issue Final Decision 20 19

- 09 Begin Post

- Decision Follow

- up 20 19 Total (years) 6

1 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).



### 1.3 Case Overview
The triclosan case (case #2340) contains one chemical, 2,4,4’

- trichloro

- 2’

- hydroxydiphenyl ether (PC Code 054901) referred herein by its standard pharmaceutical name triclosan

. Triclosan is a chlorinated aromatic compound. Triclosan was first registered by the United States on June 19, 1969 as a bacteriostat. Pres ently, there are 9 registered products under PC Code 054901

. T here

are no approved inert uses for triclosan

. Triclosan is registered for use as a bacteriostat and fungistat in plastics, polymers, and textile products during the manufacturing process to impart antibacterial properties. It is also registered for use on hard non

- porous surfaces of heating, ventilation and air conditioning ( HVAC ) exchange coils as a bacteriostat, fungistat and mildewstat. The a gency completed a Reregistration Eligibility Decision (RED) Document for triclosan in September 2008.



### 1.4 Chemical Identification and Properties

The chemical identification information for triclosan is listed in Table 3

. Triclosan 5

- Chloro

- 2

- (2,4

- dichlorophenoxy) phenol (PC Code 054901) is a substituted diphenyl ether compound containing chlorine atoms in the 2, 4, and 4’ position. It include s both phenol and ether functional groups

.

Table 3

- Chemical Identification of Triclosan

Common Name Triclosan

Chemical Name 5

- Chloro

- 2

- (2,4

- dichlorophenoxy) phenol

Classification Diphenyl ether ; Polychloro phenoxy phenol
PC Code 0 54901 CAS No. 3380

- 34

- 5 Molecular Formula C 12 H 7 Cl 3 O 2 Molecular Weight 289.541

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Page 11 of 130 Molecular Structure:



### The product chemistry information (source: MRIDs 42027902, 45358502, 42027904, 43022601, 43277801 and 45358506) relevant to risk assessment for Triclosan is summarized in Table 4

. D etails of the fate properties are discussed in Appendix B

.

Table 4

- Physical

- Chemical Properties for Triclosan

Guideline Number Physical and Chemical Properties Triclosan

830.1550 Product identity and composition Refer to Table 3
830.1650 Description of Formulation Process Confidential Business Information (CBI) 830.6302 Color White crystalline powder 830.6303 Physical State Solid 830.6304 Odor Faint odor; slight aromatic/phenolic odor.

830.6313 Stability to normal and elevated temperature, metals/metal ions Stable under ordinary conditions. No thermal effect. Stable when exposed to metals. Triclosan exposed to zinc and zinc ions showed the same decrease in percent active ingredient (ai) as control. Triclosan exposed to iron ions showed a greater decrease in percent ai than the control. 830.7000 pH Not applicable 830.7050 UV/Visible Absorption Degrades in sunlight 830.7200 Melting point 56.5°C

830.7220 Boiling point Triclosan is a solid and, therefore, has no boiling point. Decomposition temperature: >280°C 830.7300 Density 1.55 g/cm 3 at 22°C 830.7370 Dissociation Constant in water pK a =8.14 at 20°C 830.7550 Partition coefficient (n

- octanol/water) Log K ow 4.8 at 25 o C

830.7840 Solubility in water Soluble in water at 0.012 g/l at 20 ̊C . Triclosan is considered sparingly soluble in water, moderately soluble in dilute alkaline solutions (1M sodium hydroxide).

830.7860 Solubility in organic solvents Readily soluble in most organic solvents such as ethanol, methanol, diethyl ether.

n

- hexane 8.5 g/100 g at 25°C acetone > 100 g/100 g at 25°C 830.7950 Vapor pressure 5.2 x 10 - 6 mm Hg at 25°C N/A Henry’s Law Constant 5 x 10 - 9 (estimated) atm

- m 3 /mole at 25°C

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### 1.5 Use/Usage Description The products containing triclosan as the active ingredient ( ai ) include ready

- to

- use, pelleted/tableted, emulsifiable concentrate, and soluble concentrate formulations and impregnated materials. Concentrations of triclosan in these products range widely from 0.69% to ≥99%.

1.5.1 Summary of Registered Uses

Table 5 presents a summary of the registered uses of triclosan. There are currently 6 registrants and a total of 9 registered products. Triclosan is currently regist ered under FIFRA as a bacteriostat, fungistat, and mildewstat for use as a material preservative of products used in residential, public access, commercial, institutional and industrial premises.

Except for the HVAC use product, triclosan is incorporated into or coated onto materials at manufacturing facilities by liquid pour and solid/powder pour (unless restricted to closed loading). For the HVAC use product, triclosan is sprayed as a fine mist onto exchange coils by a service contractor. This product i s not available for use by home owners. There are no EPA registered products containing triclosan that can be applied directly by the homeowner ; however,

a rticles treated with triclosan are used by consumers and have the potential for post

- application resi dential exposure. Triclosan

- treated articles that may routinely be used in the residential market include, but are not limited to

, material preservative uses in mattresses, clothing, bibs, tooth brush bristles, plastic toys, plastic cutting boards, garbage bags, paper, playground equipment, sponges, furniture, carpeting, rugs, flooring, floor waxes and sealers, and footwear.

Table 5

- Triclosan Antimicrobial Use Summary

Use Application Method (liquid

pour, solid/ powder pour ) Product Application Rate EPA Registration # and Formulation

Materials Preservative

Textiles : hosiery, nurses’ uniforms, laboratory coats, intimate apparel, surgical and examination gowns, scrub suits, wall coverings, upholstery fabric, drapery fabric, blankets, cubicle curtains, mattress pads and covers, sheets and pillow covers, mattress filling materials, pillow filling fibers and air filters. Incorporation 2.00

- 5.00 % 10466

- 27

Synthetic & Cellulosic Sponges Incorporation 1.5

- 3.00 % 10466

- 42 Pigment Presscakes, Dispersions, Inks Incorporation 0.3

- 5.0 % Polymeric Systems Incorporation 2.00

- 5.00 %

Fabrics 1 Incorporation 0.8

- 1.5 %

Water

- Base Emulsions/Adhesives Incorporation 0.8

- 1.5 % Polymer Systems Incorporation 0.8

- 1.5 %

1 Includes mattress covers, tickings and pads, pillow tickings, and hosiery

.

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Page 13 of 130 Use Application Method (liquid

pour, solid/ powder pour ) Product Application Rate EPA Registration # and Formulation

Feathers & Down Incorporation 0.8

- 1.5 % Apparel: aprons, athletic shirts, bibs, dresses, footwear (including socks & i nnersoles ), general wear, gloves (consumer), gowns (medical & consumer), hosiery, intimate apparel, linings, running gear, sports apparel, trimmings, uniforms (service, medical, dental, sports), wet suits. Incorporation 0.1

- 1.00 %

42182

- 1 Construction & building materials: adhesives, awnings, bathtubs and bathtub enclosures, caulking (tub & tile), coatings (aqueous, solvent based; liquid, powder; metallic coating for plumbing fixtures, door handles, serving utensils, bed pans, floor drains, grease traps)

, concrete, flooring (concrete, epoxy, component fibers, & coatings), grout, handles & knobs, shower stalls, tile, wall coverings, whirlpools. Incorporation 0.1

- 1.00 %

Films: agricultural and mulch films 2 , bags (blanket, garbage, garment, vacuum), curtains (window, shower, cubicle), liners (garbage, trays), wraps (silage). Incorporation 0.1

- 1.00 %

Floor coverings: carpets, rugs, mats, sealer/wax components. Incorporation 0.1

- 1.00 % Home furnishings: blankets, cloths, countertops, curtains, draperies, furniture & fabrics, linens (towels, sheets, pillowcases,

etc. ) mattress & pillow ticking, mattress pads, napkins, shower curtains. Incorporation 0.1

- 1.00 %

Housewares: cutting boards, humidifier components, storage containers (for clothing, cosmetics, flowers, instruments, electronics, food & condiments), vacuum cleaner components. Incorporation 0.1

- 1.00 %

Industrial: air filters, air filtration media, appliance housings, automotive interiors, brooms, brushes, buckets, carts, closure gaskets, conveyer belts, countertops (& covers), earplugs, garbage cans, hosing (non food; non

- potable water transfer), janitorial supplie s, mops, respirator mask components, tabletops, trays, wipes. Incorporation 0.1

- 1.00 %

42182

- 1 Ice making equipment (water pans, piping, tubing, guards) I ncorporation 0.1

- 0.5 % Personal care products: bristles & handles of brushes (tooth, hair), combs, incontinence care products, razors. Incorporation 0.1

- 1.00 %

Sporting goods: boating/marine equipment, exercise & gym equipment, playground equipment. Incorporation 0.1

- 1.00 %

Miscellaneous: cards, currency, paper & paperboard (including menu materials & mulch), phones, toilets & toilet components/accessories, toys, wheels. Incorporation 0.1

- 1.00 %

Textiles and Fabrics; Apparel trimmings and linings, aprons (food service, home), athletic wear, awnings (indoor and outdoor), b ibs, b lanket bags, b lankets, brushes, carpets and rugs, Incorporation 0.1

- 2.00 % 86110

- 1

2 EPA has received a request to terminate the use of triclosan in agricultural films and mulches. If the cancellation order becomes effective and all prod uct labels are amended to remove the use, this table will be updated accordingly.

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Page 14 of 130 Use Application Method (liquid

pour, solid/ powder pour ) Product Application Rate EPA Registration # and Formulation conveyor belts, covers for counter tops, covers for table tops, cubicle curtains, door and floor mats, dresses, exercise equipment, floor coverings, food services wipes (towels), furniture fabrics, garment bags, gloves ( non

- medical), gowns (medical & consumer), hair brushes, hosiery and socks, intimate apparel (underwear), janitorial brushes and brooms, linens (towels, sheets, pillowcases, mattress covers, etc. ), mattress and pillow ticking, medical and dental clothing, m ops, paper mulch, pillow and mattress stuffing, quilt fabric, running apparel, uniforms, shoes, shoe inner soles and linings, shower curtains, silage wraps, sporting team uniforms, sportswear, sweatshirts/t

shirt, table clothes, napkins, tooth brush bristl es, uniforms, wall coverings, wet suits, window curtain and draperies Textiles and Fabrics; Incontinence care products (diapers and under pads) Incorporation 0.2

- 2.00 %

Polymers and plastics; adhesives, agricultural & mulch films 2

, combs & brushes, containers for cosmetics, conveyor belts, counter and table tops, currency, cushions, cutting boards, door & floor mats, exercise & gym equipment, floor coverings (wax, sealers, and coatings), flooring (concrete, epoxy, compo nent, fibers, & coatings of urethane, epoxy etc. ), floral containers, food distribution carts, food service trays, furniture coverings, furniture foam cushions, garbage bags and trash can liners, garbage cans, grease traps, medical & dental trays, menu
mat erials, playground equipment & furniture, portable toilets, sponges (cellulose), shoe inner soles, storage containers (for clothing, instruments, electronics, food & condiments), tile (wall & floor) & grout, toilet seats, toilets and urinals, tooth brush h andles, mop buckets toys, mops & mop components, pallets, paper and paperboard products, personnel cards (credit cards, driver's license, etc), tray liners, waste bins, wheel for medical carts, x

- ray holders, metallic coatings for plumbing fixtures, door h andles, serving utensils, bed pans, and floor drains Incorporation 0.1

- 1.00%

Industrial Processes and Water S ystems

HVAC coils Airless s pray er Not listed 82 5 23

- 1



### 1.5.2 Usage Information According to the Kline Biocides Report for 2004/2005 (Kline, 2005), the estimated volume consumption for triclosan in 2004 was 120,000 pounds and this entire amount was used in plastics. Triclosan makes up 16 percent of the estimated U.S . consumption of specialty biocides in plastics by v olume and 6 percent by value. The consumption in plastics was forecasted to grow at an annual rate of 1.5 percent through 2009.

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Page 15 of 130 The Kline Report also notes that: “The exceptional growth previously expected for triclosan over the last five years has not realized due to several factors, including the EPA’s ruling on public health claims. This “Treated Articles Exemption” only allows for claims that biocides protect the integrity of the plastic, and d isallows antimicrobial claims, for instance for an antimicrobial cutting board or countertop, unless that consumer product itself is registered with the EPA”



### 1.6 Regulatory History The most recent comprehensive risk assessment performed by OPP on triclosan was conducted in support of the 2008 Reregistration Eligibility Decision (RED). As part of the RED, OPP performed a comprehensive review of the hazards, exposures and risks to huma n health and the environment resulting from the registered pesticidal uses of triclosan. In support of the RED an aggregate exposure risk assessment was performed for post

- application residential exposures to triclosan using the National Health and Nutriti on Examination Survey (NHANES) biological monitoring data collected by the Center for Disease Control and Prevention (CDC). NHANES is a program designed to assess the health and nutritional status of adults and children in the United States by examining a nationally representative sample of about 5,000 persons each year ( http://www.cdc.gov/nchs/nhanes/about_nhanes.htm ). The aggregate risk assessment took all post

- application exposures to triclo san into account including both EPA

- registered antimicrobial uses and US Food and Drug Administration ( FDA )

- regulated uses such as triclosan

- containing toothpaste, hand soaps, and deodorants. Based on available data at that time, the a gency concluded tha t total exposure to triclosan from all sources did not present risks of concern for human health.

The agency conducted a qualitative environmental risk assessment as part of the RED using existing ecotoxicity studies, USGS monitored levels of triclosan fo und in waterways and

consumer product environmental modeling. The a gency determined that estimated concentrations of triclosan in surface water, when adjusted to represent concentrations from pesticidal uses only, did not exceed levels of concern for acute risk and were not likely to result in chronic risk . The a gency issued a post

- RED Data Call

- In (DCI) requiring monitoring data on the effluent of manufacturing facilities using triclosan. These monitoring data, along with effects data anticipated to be needed for the registration review , will be utilized to conduct a quantitative risk assessment during registration review. All currently registered pesticidal uses of triclosan were found eligible for reregistration in 2008. (Use of tri closan as a material preservative in paint was found ineligible

. T he registrant requested voluntary cancellation ; the paint uses for triclosan will be removed from product labels prior to risk assessment, see section 1. 6 .1 .)

In response to the research o n human health eff ec ts (US EPA / Office of Research and Development) that was ongoing at the time of the RED and public concern regarding triclosan, the a gency decided to undertake another comprehensive review of triclosan under the Registration Review Program in Fiscal Year 2013. Since 2008, OPP has engaged in several key

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Page 16 of 130 efforts that will ensure that our review of triclosan is timely, scientifically sound and transparent, with appropriate public participation.

In the RED, the a gency acknowledged scientific literature suggesting potential endocrine effects of triclosan and committed to examining the endocrine interactions of triclosan further. Since 2008, the Of fice of Pesticide Programs has collaborated with the EPA’s Office of Research and Development (ORD) on the conduct of additional studies to investigate the endocrine effects of triclosan. In particular, ORD investigated the effects on the androgen, estroge n, and thyroid hormone systems using a variety of experimental approaches. The a gency presented some of this information as part of a case study during the “Integrated Approaches to Testing and Assessment strategies (IATA): Use of New Computational and Mol ecular Tools” FIFRA Scientific Advisory Panel (SAP) consultation in May, 2011 . The triclosan case study presented to the SAP was not a full risk assessment.

As background information for the case study presented at the SAP, the a gency also released an

up dated draft exposure assessment for triclosan that incorporated NHANES data that became available after the completion of the 2008 RED. The draft exposure assessment included NHANES data for ’05

- ’06 and ’07

- ’08 in addition to the ’03

- ’04 data that the a gen cy utilized for the RED risk assessment. The a gency has not developed any new conclusions regarding the impacts of triclosan on human health as a result of the case study or updated exposure assessment. Both the research conducted by ORD and the updated NH ANES data will be taken into account during the comprehensive human health risk assessment that will be performed as part of the registration review of triclosan. Documents related to the SAP can be found at regulations.gov in docket EPA

- HQ

- OPP

- 2011

- 0284.

1.6.1 Recent/Pending Regulatory Actions

In March 2013 the a gency received a request to amend triclosan labels for EPA registration numbers 42182

- 1 and 42182

- 7 to terminate the use in agricultural films and mulches. The amendment for EPA Reg. No. 42182

- 1 now incorporates the recommendations made in the 2008 RED. EPA registration number 42182

- 7 is under review. EPA publish ed a notice in the Federal Register announcing the receipt of the request pursuant to FIFRA section 6(f) on July 25, 2013, the notice can be found on regulations.gov in docket EPA

- HQ

- OPP

- 2013

- 0480

- 0001

. In 2012 and 2013 the EPA published Cancellation Orders for EPA Registration Numbers 2829

- 139, 2829

- 145, 4822

- 429, 3090

- 165, 5383

- 127 and 10466

- 24 as a result of requests for voluntary cancellati on. EPA Registration Number 83884

- 7 was cancelled in 2012.

Citizen’s Petition for a Ban on Triclosan

On January 14, 2010 Beyond Pesticides and Food & Water Watch submitted The Citizens Petition for a Ban on Triclosan to the U.S. Environmental Protection A gency (EPA). The petition specifically request ed that the a gency take the following steps under each of the following statutes:

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Page 17 of 130 FIFRA and FFDCA : (1) reopen the Reregistration Eligibility Decision (RED) (2) issue a notice of cancellation of the registrations of all products containing triclosan and (3) concurrently issue an emergency order to immediately suspend the existing triclosan registrations ;

CWA: (1) impose technology

- based effluent limitations, (2) establish health

- based toxic pollutant water quality pretreatment requirements and (3) impose biosolids regulation for triclosan ;

SDWA: (1) conduct a comprehensive assessment of the appropriateness of regulating triclosan under SDWA ; and

ESA: (1) conduct a biological assessment and (2) engag e in consultation with the Secretary of the Interior and the Secretary of Commerce

.

All information submitted as part of the petition and during the comment period for the petition is available in docket EPA

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- 2010

- 0548. The a gency’s response will also be made available in that docket. The response to the petition’s requests for relief under FIFRA will be a final action by EPA independent of the registration review process. However, the petitioners, along with the public in general, will have mult iple opportunities to participate in the registration review when they can contribute to the discussion of any scientific issues in relation to data developed since the RED, as well as any data that are submitted as part of this registration review.

Asses sments by Other Regulatory Agencies

In December of 2013, FDA issued a proposed rule 3 

### that would require manufacturers to provide additional data to support the safety and effectiveness of consumer antiseptic handwashes. For triclosan, FDA's focus is on the use by consumers on a regular basis in hand soaps and body washes. The FDA may requ ire additional data to determine the potential for hormonal effects as well as the relevance of antimicrobial resistance to the consumer setting

. H owever, the EPA does not anticipate the need to require additional endocrine data for the pesticidal uses of triclosan. Prior to release of the proposed rule, the EPA and the FDA closely collaborated on science and regulatory issues related to triclosan. FDA’s regulations implementing NEPA (21 CFR part 25) do not require an environmental assessment or environment al impact statement for FDA’s proposed rule because it will not result in an increase in the use of the active ingredients that are

3 FDA’s proposed rule is available at: https://www.federalregister.gov/articles/2013/12/17/2013

- 29814/safety

- and

effectiveness

- of

- consumer

- antiseptics

- topical

- antimicrobial

- drug

- products

- for

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Page 18 of 130 the subject of the proposed rule, including triclosan. In the Preliminary Regulatory Impact Analysis for the proposed rule, FDA estimates that a benefit of the proposed rule would be a significant reduction in triclosan exposure. A decrease in human exposure from these uses would translate to a decre ase in environmental impact.

In 2012, Health Canada and Environment Canada join tly published a preliminary assessment 4 

### of the human health effects and environmental toxicity of triclosan. In Canada, triclosan is subject to regulation under the Pest Control Products Act (PCPA) (Canada 2002), the Food and Drugs
Act (Canada 1985) and t he Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada 1999). In that preliminary assessment, triclosan exposure and risk were assessed from exposure to triclosan in consumer products treated with or containing triclosan (including, but not limited to, cosmetic products, treated textiles and food contact materials, such as cutting board s and countertops), drinking water contaminated with triclosan, breast milk, and contaminated household dust. Exposure of the general population to triclosan was characterized using the available biomonitoring data for triclosan from the US National Health and Nutrition Examination Surveys (NHANES). In the absence of Canadian

- specific data for the general population, the biomonitoring data for the US population were used. Additional Canadian biomonitoring data were used to characterize the exposure of child ren under the age of 6 years to triclosan. Environmental exposures were assessed using measured data for concentrations of triclosan at WWTPs as well as in receiving surface water. Under CEPA 1999, Health and Environment Canada concluded that triclosan is not entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health. However, it was concluded that with respect to the environment, triclosan “is entering or may ent er the environment in a quantity or concentration or under conditions that have or may have an immediate or long

- term harmful effect on the environment or its biological diversity.” Under the PCPA, Health Canada concluded that the use of pest control produ cts containing triclosan in Canada does not pose an unacceptable risk to human health. While use of these products may contribute to environmental exposure to triclosan, given the registered uses and the life cycle of triclosan treated products (e.g., trea ted plastics, textiles, leather, paper and rubber), pest control products are not expected to contribute significantly to the risks to aquatic organisms.

In 2009, the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) within the Au stralia Government Department of Health and Ageing published a full risk

assessment 5 

### on the public health, occupational health and safety, and environmental effects of industrial uses of triclosan

. Triclosan is not manufactured in Australia but is imported for use in the formulation of personal care and cosmetic products; therapeutic products; cleaning agents; in

4 Health Canada and Environment Canada ’s preliminary assessment is available at http://www.chemicalsubstanceschimiques.gc.ca/plan/approach

- approche/triclosan

- eng.php
5 NICNAS’ risk assessment is available at: http://www.nicnas.gov.au/Publications/CAR/PEC/PEC30/PEC_30_overview_PDF.pdf

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Page 19 of 130 the treatment of textiles and in plastics manufacture; in the formulation of some oil

- based paints; and in grouting material

. That assessment con cluded that under normal conditions of exposure for occupational workers and under normal conditions of use for residential populations, the risk of adverse effects from exposure to triclosan was low. It was acknowledged that repeated use of cosmetic prod ucts containing triclosan could lead to increased levels of exposure and thus to increased risk. With regard to environmental risk, it was concluded that there was no evidence that the use of triclosan was leading to development of triclosan

- resistant bac terial populations or any increased risk to humans regarding antibiotic resistance. The assessment identified that triclosan is highly toxic to a number of freshwater aquatic organisms, with freshwater algae being the most sensitive species. The major envi ronmental release of triclosan in Australia was identified as from wastewater treatment plants. As such, the assessment concluded that at current levels of use, the release of triclosan to the environment, the risk to fish and aquatic plants are at worst ‘marginal,’ but that adverse effects on algae could result from current levels in the environment. The application of biosolids containing triclosan to fields was identified as an area of concern for which more study of the effect of triclosan on microbial soil populations was identified.

1.6.2 Tolerance Information There are no tolerances or tolerance exemptions for triclosan. The need for tolerance s or tolerance exemptions will be revisited during registration review.



### 1.7 Incidents

1.7.1 Human Health

Eight triclosan related cases have been reported in OPP’s Incident Data System (IDS) for the time period spanning 2002 to 2011. Among the reported incidents, only one incident is considered triclosan

- specific. The incident was reported to the a gency in January of 2011 a nd involv ed symptoms in an individual who had hand washed a small amount of clothing with an anti

- bacterial hand soap containing 0.15% triclosan. The individual reported symptoms including allergic reactions, headache, chemical taste in the mouth, complete loss of appetite, muscle twitches, and atrophy. The individual also reported that he had developed a full blown chemical sensitivity to triclosan. These symptoms were reported by the individual and no further details of the symptoms were provided, nor wer e these symptoms verified by a doctor or other health professional. The specific amount of triclosan to which the individual was exposed could not be determined fr om the description provided.

1.7.2 Ecological
No incidents involving triclosan were reported in t he following databases as of February 7 , 201 3 : Ecological Incident Information System, version 2.1.1, the Aggregate Incident Data System, and the Avian Incident Monitoring System (AIMS) 6



### .

6 http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/index.cfm

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Page 20 of 130 

## 2 Anticipated Data Needs

Several studies were required as confirmatory data from the assessment of Triclosan in the RED. In addition to the already

- required RED DCI data

, t he following studies as listed in Table 6 are expected to be needed for the registration review of Triclosan

. Table 7 outlines the data requirements required by the post

- RED DCI issued on October 5, 2011

. The a gency anticipates reviewing any data received in response to the post

- RED DCI as well as data requested for this registration review prior to conducting the registration review risk assessments for triclosan.

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Page 21 of 130 Table 6

– Studies Anticipated as Needed for Registration Review of Triclosan

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

Special Study 1

, 2 Leaching from plastic agricultural mulch TGAI 24 Environmental Fate, Ecological Plastic/polymer agricultural mulch/film In

- service use

850.1025 3, 5 or 850.1055 Acute mollusk TGAI 12 Ecological Textile application, plastic/polymer agricultural mulch/film Effluent discharge and in

- service use, respectively

850.1035 3, 5 Mysid acute TGAI 12 Ecological Textile application, plastic/polymer agricultural mulch/film Effluent discharge and in

- service use, respectively

850.1300 3, 4

, 5 Daphnid Life Cycle study TGAI 12 Ecological Textile application, plastic/polymer agricultural mulch/film Effluent discharge and in

- service use, respectively

850.1350 3

, 5 Mysid life cycle TGAI 12 Ecological Textile application, plastic/polymer agricultural mulch/film Effluent discharge and in

- service use, respectively

850.1500 1, 3, 4

, 5 Freshwater fish full life cycle TGAI 24 Ecological Textile application, plastic/polymer agricultural mulch/film Effluent discharge and in

- service use, respectively

850.33 0 0 or OECD 209 Activated Sludge

, Respiration Inhibition (ASRI) TGAI 24 Environmental Fate, Ecological Textile application

, plastic/polymer agricultural mulch/film Discharge to WWTP, effluent discharge

875.1200 Indoor Exposure, Dermal MP; EP 24 Occupational HVAC coils Airless sprayer

875.1400 Indoor Exposure, Inhalation MP; EP 24 Occupational HVAC coils Airless sprayer

1 The anticipated DCI will require that a p rotocol be submitted to the Agency for review and approval prior to conduct of the study

. 2 EPA has received a request to terminate the use of triclosan in agricultural films and mulches. If the cancellation order becomes effective and all product labels are amended to remove the use, this anticipated data requirement should no longer be needed

. 3 This study, previously held in reserve in the RED, is expected to be required for registration review (see Appendix C )

.

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Page 22 of 130 4 An acute value is expected to be required for the same species used in the fish full life cycle test to allow calculation of an acut e

- to

- chronic ratio (ACR) for use in predicting a chronic value for the most acutely sensitive freshwater species.
5 The anticipated DCI will require that testing under acidic, neutral and basic pH conditions be tested or alternatively, at a minimum that the study be conducted under acidic pH conditions that optimize the unionized state, which is generally considered the more bioavailable and toxic s tate, but which would also still be within the guideline biological pH range for the test species. With a pKa of around 7.9

- 8.1, at pH conditions of around 7.9

- 8.1 half of the triclosan is expected to be in the unionized and half in the ionized state.



### Table 7

– Data Needs Required by the October 5, 2011 Data Call

- In for the Triclosan RED

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

850.1730 Fish BCF PAIRA; TGAI 12 Environmental Fate, Ecological Residential and public access premises; materials preservatives; aquatic non

- food industrial use

850.1710 Oyster BCF PAIRA; TGAI 12 Ecological Residential and public access premises; materials preservatives; aquatic non

- food industrial use

850.1850 1 Aquatic Food Chain Transfer PAIRA; TGAI 24 Ecological Residential and public access premises; materials preservatives; aquatic non

- food industrial use

SS

- 2 2 Chronic Sediment Toxicity MP; PAI; TGAI 24 Ecological Residential and public access premises; materials preservatives; aquatic non

- food industrial use

875.1200 Indoor Exposure, Dermal MP; EP 24 Occupational M aterials preservatives Powder pour

875.1400 Indoor Exposure, Inhalation MP; EP 24 Occupational M aterials preservatives Powder pour

875.1700 Product Use Information ALL 12 All All All

875.2300 Indoor Surface Residue Dissipation EP 24 Residential Material preservative use in plastics (toys) Mouthing plastic toys

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Page 23 of 130 GLN Study Name Test Substance Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Triggering Data Requirement Applicable Exposure Scenario

875.2700 Product Use Information ALL 12 All All All

875.2800 Description of Human Activity ALL 12 All All All

Source of post

- RED DCI: EPA Docket EPA

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- 2007

- 05 1 3

- 0066, GDCI 054901

- 30197

1 Study held in reserve in the RED pending the outcome of surface water monitoring studies, the fish bioconcentration factor, a nd the oyster bioconcentration factor studies

2 Three chronic spiked

- sediment studies are required, two with freshwater (midge and amphipod ( Hyallela azteca )) and one with an estuarine/marine amphipod species.

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Page 24 of 130 

## 3 Human Health Risk Assessment

3.1 Existing Toxicological Endpoints

The endpoints listed in Table 8 were used in the human health risk assessments for the Triclosan RED. All i nformation

, including existing toxicology studies, valid scientific literature and the studies that are expected to be required for registration review will be considered in the final risk
assessment for OPP

.

S ummary information on the interaction of triclosan with the endocrine hormone system

, including interaction with the thyroid, estrogen, and androgen hormone systems , was included in the 2008 RED . As part of the registration review, these data about interaction of triclosan with the endocrine system will be included in the risk assessment.

With respect to human health risk assessments, the petition raised the issue of whether triclosan may result in human exposure to dioxins. The a gency will evaluate available information to determine the extent to which this registration review will address potential human exposure to dioxins from triclosan

.

Table 8

- Toxicological Endpoints Used for the Triclosan RED

Exposure Scenario Dose Used in Risk Assessment Uncertainty factors for Risk Assessment Study and Toxicological Effects 

### Acute Dietary

(gen. pop.) NOAEL = 30 mg/kg

aRfD = 0.03 mg/kg/day Interspecies = 10x

Intraspecies = 10x

DB* = 1x

UF = 100 Chronic Toxicity study in Baboons

MRID 133230

Acute Dietary

(females 13+) No appropriate endpoint identified in the database

Chronic Dietary

(all populations) NOAEL = 30 mg/kg

cRfD = 0.03 mg/kg/day Interspecies = 10x

Intraspecies = 10x

DB* = 1x

UF = 100 Chronic Toxicity study in Baboons

MRID 133230

LOAEL = 100 mg/kg/day, based on clinical signs of toxicity

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Page 25 of 130 Exposure Scenario Dose Used in Risk Assessment Uncertainty factors for Risk Assessment Study and Toxicological Effects



### Short

- Term/ Intermediate

Term Incidental Oral (1

- 30 days; 30 days

- 6 months) NOAEL = 30 mg/kg Interspecies = 10x

Intraspecies = 10x

DB* = 1x

UF = 100 Chronic Toxicity study in Baboons

MRID 133230

LOAEL = 100 mg/kg/day, based on clinical signs of toxicity

Dermal (short

term) NOAEL = 0.6 mg/animal (100 μg/cm 2 

### ) Interspecies = 3x

Intraspecies = 3x

DB* =1x

MOE = 10 14

- day dermal toxicity study in the mouse

MRID 44389708

LOAEL = 1.5 mg/kg/day, based

on treatment

- related dermal irritation at the treatment site and on increased liver weights

Dermal (intermediate term) NOAEL = 40 mg/kg Interspecies = 10x

Intraspecies = 10x

DB* =1x

MOE = 100 90

- day Dermal Toxicity in Rats

MRID 43328001

LOAEL = 80 mg/kg/day, based on increased incidence occult blood in the urine.

Dermal (long

term) NOAEL = 40 mg/kg Interspecies = 10x

Intraspecies = 10x

DB* =3x (lack of chronic dermal study)

MOE = 300 90

- day Dermal Toxicity in Rats

MRID 43328001

LOAEL = 80 mg/kg/day, based on increased incidence occult blood in the urine.

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Page 26 of 130 Exposure Scenario Dose Used in Risk Assessment Uncertainty factors for Risk Assessment Study and Toxicological Effects 

### Inhalation (all durations) NOAEL = 50 mg/m 3 

### or 3.21 mg/kg/day

Where mg/kg/day = ((0.0087 m3/hr * mg/m3 * 2 hr/day) /0.271 b.w. MOE = 1000 21

- Day Inhalation Toxicity study in the rat

MRID 0087996

LOAEL = 0.115 mg/L, based on increased total leukocyte count and increased serum alkaline phosphata se

Cancer (oral) In accordance with the EPA Final Guidelines for Carcinogen Risk Assessment (March 29, 2005), the HED CARC classified triclosan as “Not Likely to be Carcinogenic to Humans”.

UF = uncertainty factor, DB = database uncertainty [special sensitivity] factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose, MOE = mar gin of exposure, LOC = level of concern, NA = Not Applicable



### 3.2 Dietary Exposure

The u se of products containing triclosan may result in indirect dietary exposure, i.e. exposure to food as a result of the use of triclosan in paper, adhesives , countertops, cutting boards, ice

making equipment, and conveyor belts. Exposure attributable to t hese uses was included in the aggregate assessment in the 2008 RED

, and no dietary risks of concern were identified. Potential secondary (or indirect) d ietary exposure will be included in the aggregate assessment for this registration review (see 3.4.1) based on the National Health and Nutrition Examination Surveys (NHANES) biological monitoring data because these data reflect all exposures

.



### 3.3 Occupationa l and Residential Exposures

Representative occupational handler exposures were assessed in the 2008 RED for HVAC coil applications, painting scenarios, and pulp and paper mill use. Surrogate unit exposure data primarily from the proprietary Chemical Manuf acturers Association (CMA) Antimicrobial Exposure Study (USEPA, 1999) and the Pesticide Handlers Exposure Database (PHED; USEPA, 1999) were used to assess handler risk. Use of triclosan as a material preservative in paint was found ineligible . T he registra nt requested voluntary cancellation. The paint uses for tric l osan will be removed from product labels prior to risk assessment; therefore, a residential handler exposure assessment is not anticipated to be needed for registration review

.

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Page 27 of 130 3.3.1 Occupational Han dler Exposures

EPA anticipates the need to conduct an occupational exposure assessment on the HVAC use and
on ope n pouring/mixing of triclosan during material preservation

.

Table 9

- Occupational Handler Exposure Scenarios for Triclosan

Scenario Exposure Route(s) Duration

Occupational Exposures

Airless spray application to HVAC coils Dermal Inhalation Short, Intermediate

Open pouring/mixing of powder during material preservation 6 Dermal Inhalation Short

, Intermediate, and Long
Term

6 These data have already been required by the Post

- RED DCI issued on October 5, 2011.



### 3.3.2 Residential Handler Exposures

Because residential handler exposure is not expected to occur , a residential handler exposure assessment is not anticipated for this registration review.

3.3.3 Residential Post

- Application Exposures Residential post

- application exposure is expected to occur from the use of EPA

- registered products containing triclosan in textiles and fabrics ( e.g. , mattresses and clothing/bibs) and plastic products ( e.g. , toys, cutting boards, etc). Potential exposures also include EPA

- registered uses where there is the possibility of indirect migration to food , including paper/pulp use, use in ice

- making equipment, adhesives, cutting boards, and counter tops as well use in conveyer belts. In addition to EPA

- regulated uses, residential post

- application exposure is expected to occur from the FDA

- regulated uses such as toothpaste, hand soap s, and deodorants.

Residential post

- application exposures for this registration review will be included in the aggregate assessment (see 3.4.1) based on the NHANES biological monitoring data.

For the 2008 RED, EPA conducted the residential post

- applica tion exposure assessment for triclosan using the biomonitoring data available through NHANES. This approach was adopted by EPA because of the need to assess aggregate exposure that is expected from co

- use of different consumer products containing triclosa n. The NHANES monitoring data provides the most representative measure of aggregate exposures to daily use products. In the case of triclosan, population

- based biological monitoring data are available to assess the co

- occurrence of uses to develop an agg regate exposure assessment for ages 6 years and older. The population

based biological monitoring data are the best predictor of aggregate exposure because not only are the data triclosan specific, they are also based on actual consumer use of the variou s triclosan products as they co

- occur in practice and would include drinking water exposures as well. EPA

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Page 28 of 130 intends to use the latest available NHANES biomonitoring data for assessment of residential post

- application exposures to triclosan in the registrati on review risk assessment.



### 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures In examining aggregate exposure, EPA takes into account the available and reliable information concerning exposures to pesticide residues in food and drinking water, as well as non

occupational ( i.e. residential) pesticide exposures. An aggregate exposure assessment for triclosan was presented as part of the background documentation for the 2011 FIFRA SAP meeting using the NHANES database

. For this registration review, EPA plans to conduct an aggregate assessment to account for exposure to triclosan from dietary and residential post

- application exposures. The aggregate assessment will estimate risk based on the aggregated exposure of EPA and FDA uses using the NHANES bio logical monitoring data. The NHANES databases are a series of U.S. national surveys of the health and nutrition status of the non

- institutionalized civilian population conducted by the Centers for Disease Control and Prevention (CDC). EPA believes the NHA NES dataset provides the most comprehensive data on exposure to triclosan from all sources (dietary and non

- dietary as well as both EPA

- and FDA

- registered uses) and is the best dataset for estimating aggregate risk to triclosan. These data account for bo th indirect dietary exposures and exposures through drinking water more effectively than the standard models normally used by the a gency to estimate exposures. However, because the NHANES methodology used to collect the samples from the general population does not allow EPA to distinguish the contribution of products regulated by EPA and those regulated by FDA, the residential assessment planned for registration review will estimate residential risk from all uses for triclosan. For the 2008 RED, NHANES dat a were available for triclosan only for the 2003

- 2004 survey cycle. Subsequently, CDC has released the triclosan results for the 2005

- 2006, 2007

- 2008, and 2009

- 2010 survey years. These data will be used for the registration review risk assessment of tric losan exposure.

Although the aggregate exposures presented using the NHANES data are considered to include all triclosan exposures , it does not include exposures to children under the age of 6 years old. Children under the age of 6 years exhibit unique a ctivities that do not occur at older ages. Therefore, a separate estimate for children under 6 years old will be included in the registration review risk assessment and t he most up

- to

- date information available will be considered provided the information complies with EPA’s Rule on Protections for Subjects in Human Research Involving Pesticides.

3.4.2 Cumulative Exposures Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a com mon mechanism of toxicity finding for

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Page 29 of 130 triclosan and any other substances. For the purposes of this registration review, therefore, EPA has not assumed that triclosan has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning common mechanism determinations and proce dures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.



## 4 Environmental Risk Assessment
An ecological risk assessment was conducted for the RED (EPA 2008). Due to lack of available ecotoxicity data, that assessment only addressed acute risk to freshwater fish and invertebrates, and risks to aquatic plants and acute hazards to birds and mamma ls

. Acute risks to estuarine/marine fish and invertebrates and chronic, reproductive risks to freshwater fish and invertebrates and estuarine/marine fish and invertebrates were not assessed. Exposure to aquatic organisms was based on monitoring data repo rted in the published literature, including U. S. Geological Survey (USGS) monitoring data for U. S. waterways, and from down

- the

- drain modeling. However, t he waterway concentrations include all sources of triclosan, not just antimicrobial uses. To evalu ate risks attributable to the antimicrobial pesticidal uses (rather than monitoring data which is primarily from personal care product uses or a mixture of these two), studies specifically designed to monitor the pesticidal textile and plastic manufacturin g uses were called

- in as part of the post

- RED DCI (GDCI 054901

- 30197, October 5, 2011).

The a gency has not conducted a risk assessment that supports a complete endangered species determination for triclosan . The ecological risk assessment planned during re gistration review will allow the a gency to determine whether use s of triclosan ha ve 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a p esticide’s use 'may affect' a listed species or its designated critical habitat, the a gency 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 The conceptual model for the triclosan pesticidal use with potential environmental exposure is in Figure 1

. The t riclosan use scenarios with potential for environmental exposures of concern include material preservative uses which result in discharge to waste water treatment plants such as applic ation to textiles

. Discharge to WWTPs from leaching of triclosan during in

- service use of treated textiles in homes, institutions, etc. is identified as not likely to contribute significantly to risks from the pesticidal uses of triclosan, as reflected by dashed lines in Figure 1. EPA performed a screening

- level assessment to determine whether triclosan released to municipal wastewater treatment plants (WWTPs) from in

- service uses of any materials preserved with triclosan (pesticidal uses) would be expecte d to lead to potential risks of concern to aquatic

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Page 30 of 130 organisms downstream of WWTPs 7



### . No environmental exposure from the application of triclosan to plastic is expected because the label prohibits use in plastic manufacturing processes which would result in c ontact and transfer of triclosan with process water that would be discharged to a WWTP or to surface water . Of the in

- service uses of plastic

, the agricultural films and mulch have the potential to result in leaching to agricultural fields

. None of the other material preservative uses and application methods (e.g., incorporation in concrete, adhesives, etc.) would result in contact and discharge of triclosan to wastewater

. The conceptual models for

uses with potential environmental exposure a re in Figure 1 and Figure 2

. 8

PCEs (p rimary constituent elements ) are those physical and biological features of a landscape that a species needs to survive and reproduce. For federally listed species, PCEs are listed with the critical habitat http://nctc .fws.gov/resources/knowledge

resources/Pubs9/critical_habitat00.pdf

. 

### Figure 1

- Conceptual Model for Environ mental Exposure from Treatment of Textiles with Triclosan

7 For more information about the screening level assessment assumptions, see Section 4.3.4 of this FWP.
8 EPA has received a request to terminate the use of triclosan in agricultural films and mulches. If the cancellation order becomes effective and all product labels are amended to r emove the use, th ese conceptual models will be adjusted accordingly.



### 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 Surface Water/Sediment

Aquatic Animals Invertebrates Vertebrates 

### Exposure Media

Ingestion Ingestion Uptake/gills or integument

Aquatic Plants
Non

- vascular Vascular Uptake or sorption/cell, 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 WWTP microorganisms Uptake or sorption

Population Respiration inhibition Textile (Exhaust, Padding)
Treatment Process

Facility Drain In

- Use Service of Treated Textiles

Washing/Leaching

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Page 31 of 130 PCEs (p rimary constituent elements ) are those physical and biological features of a landscape that a species needs to survive and reproduce. For federally listed species, PCEs are listed with the critical habitat http://nctc.fws.gov/resources/knowledge

resources/Pubs9/critical_habitat00.pd f

. 

### Figure 2

- Conceptual Model for Environmental Exposure from In

- Service Use of Triclosan in Plastic Agricultural Film and Mulch



### 4.2 Ecological Effects Assessment Ecological effects data are used as measures of direct and indirect effects to biological receptors. Acute and chronic toxicity data from studies submitted by pesticide registrants along with the available open literature will be used to evaluate the potential direct and indirect effects of triclosan to aquatic and terrestrial receptors. Current selected ecotoxicological endpoints are summarized in Table 10

. A more detailed description of the ecotoxicity studies is provided in Appendix C

.

4.2.1 Mechanism of Action

IFDA (2008) identifies that triclosan has two mechanisms of action. One mechanism is via insertion into bacterial cell membranes and disruption of membrane activities without causing leakage of intracellular components. The second mechanism of action is inhi biti on of bacterial fatty acid synthesis at the enoyl

- acyl carrier protein reductase step. Fatty acid synthesis is critical

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 Surface Water/Sediment

Aquatic Animals Invertebrates Vertebrates 

### Exposure Media

Ingestion Ingestion Uptake/gills or integument

Aquatic Plants
Non

- vascular Vascular Uptake or sorption/cell, 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 Key Most likely

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

- Service Use of Plastic Agricultural Mulch Treated

Leaching and Run

- off

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Page 32 of 130 for building of cell membranes and reproduction. This enzyme is found in bacteria, fungi, and some plants. In algae triclosan has been observed to compromise lipid biosynthesis, cell membrane integrity and photosynthesis.

4.2.2 Measures of Effect (Ecotoxicology Endpoints) Current selected ecotoxicological endpoints for conducting the risk assessment are provided in Table 10

. All availabl e ecotoxicity endpoints from studies submitted by registrants are tabulated in Appendix C. The ag ency recognizes that there are additional data available on triclosan effects in the open literature. Part of the analysis plan includes a literature search and review of such data for inclusion in the risk assessment as needed. The a gency uses the most sensitive acceptable toxicity values for assessing risk to each receptor group. Endpoint data gaps are indicated.

No endpoints were selected for dioxin or methyltriclosan transformation products

. From a preliminary examination of which d ioxins are formed from triclosan in chlorinated waters (2,7

- dibenzodichloro

- p

- dioxin; 2,8

- dichloro

- p

- dioxin; 1,2,8

- and 2,3,7

- trichlorodioxins and 1,2,3,8

- tetrachlorodioxin) , they are not among congeners of toxicological concern (see Appendices B and F ) and no endpoints were selected for the assessment

. Additionally, methyltriclosan was not detected in effluent monitoring studies for textiles ( < 1.9 n anograms per liter (n g/L ) ) and therefore no endpoints are included.

Table 10

- Effects Endpoints for the Ecological Risk Assessment of Triclosan

Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Comment Reference/ Study Classification

Freshwater fish Fathead minnow Acute 96

- h LC 50 = 2 88 a μg ai/L 43969301

Rainbow
trout Chronic F ish full life cycle da ta required An acceptable acute 96

- h LC 50 study is expected to be required for the species used in

the fish full life cycle to allow calculation of an ACR
Freshwater invertebrates Waterflea Acute 48

- h EC 50 = 390 μg ai/L 430460

- 02
Chronic Data required Freshwater benthic invertebrates Midge Chronic NOAEC >100 mg ai/kg 475866

- 01

Estuarine/marine fish Sheepshead minnow Acute 96

- h LC 50 = 716,000 μg ai/L Web

- ICE v3.1

Chronic Data anticipated to be required Plan to model from acute

- to

chronic ratios (ACRs).

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Page 33 of 130 Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Comment Reference/ Study Classification

Estuarine/marine invertebrates Mysid Shrimp Acute Data anticipated to be required

Chronic Data anticipated to be required
Oyster Acute Data anticipated to be required

Estuarine/marine benthic invertebrates Chronic No d ata in addition to that already required under the post

- RED DCI

are anticipated
Algae and Cyanobacteria Green algae EC 50 0.7 μg ai/L Orvos et al . 2002 NOAEC 0.5 μg ai/L

Aquatic vascular plants Duckweed EC 50 EC 50 >62.5 μg ai/L 444228 01

NOAEC Not determined

Birds Mallard Acute LD 50 = 82 2 mg ai/kg bw 430226 02

Chronic Not required NA

Mammals Rat Acute LD 50 > 5000 mg/kg 43206901

Chronic NOAEC = 50 mg ai /kg

bw /day 40623701
Nontarget insects Acute Not required N/A

a Value reported here was calculated using mean measured concentration. Because triclosan was not stable during the study, a value using concentrations measured at the end of the exposure period will be evaluated.



### 4.3 Exposure Analysis Plan During the risk assessment phase of registration review, the a gency will review environmental fate and exposure from submitted guideline studies, open liter ature, and government databases. Impacts on the understanding of the fate of triclosan and its major degradates, and the exposure approach and risk assessment approach described in this work plan will be taken into consideration during the risk assessment phase of registration review.

4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates In order to address the risk hypothesis, estimates of environmental exposure will be based on the use for textile treatment (which consists of discharge from textile manufact uring sites) and the
in

- service use of agricultural mulch conceptual models. For in

- service use of agricultural mulch impregnated with triclosan, PRZM/EXAMS will be used to estimate runoff and loading to surface water from agricultural fields covered with agricultural mulch impregnated with triclosan 9 

### . No information on the leach rate from plastic agricultural mulch is available for use

9 EPA has received a request to terminate the use of triclosan in agricultural films and mulches. If the cancellation order becomes effective and all product labels are amended to remove the use, th is section will be updated accordingly.

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Page 34 of 130 in PRZM modeling. Conservative estimates of triclosan leaching from plastic, such as 100% leaching, will be used unless information on leaching from plastics is submitted or found from open literature to refine estimates of leaching. In the 2008 RED, surface water monitoring data was used to characterize risk from pesticidal uses

, but the available monitoring data was not specifically designed to identify exposure specifically from pesticidal ( e.g ., material preservative ) uses and more likely reflect ed contributions from FDA

- regulated uses. Monitoring data specific to material pre servative uses were called

- in as part of the post

- RED generic data call

- in (GDCI

- 054901

- 30197). These data have been submitted and found to be acceptable for use in the risk assessment. This monitoring data will be used to characterize exposure for use i n the registration review. A discussion of the monitoring data for the textile manufacturing use is discussed in Section 4.3.2.

4.3.2 Textile Manufacturing Monitoring Data In accordance with the analysis performed for the re

- registration of triclosan, EPA requir ed monitoring data on triclosan contained in effluents from textile manufacturing facilities as part of the post

- RED DCI . In support of this request, select direct

- discharging (holding valid NPDES Permits) textile manufacturing facilities, using triclosan as a material preservative, were used to determine the concentration of triclosan in textile manufacturing effluent. ENVIRON International Corporation on behalf of Microban International, Ltd conducted monitoring in 2012. Two textile facilities were cho sen to collect data on the concentrations of triclosan and methyl triclosan present in their effluent after triclosan was applied to textiles using the exhaustion process. This process uses a dye

- bath ( i.e . jet machine) to apply triclosan and other ingredients to textiles at high temperature. The spent or remaining solution from the exhaustion process is discharged to on

- site wastewater treatment plants before the resulting effluent is discharged to surfac e waters. The discharge to surface waters at these facilities is conducted under National Pollutant Discharge Elimination System (NPDES) permits. Sampling intervals and frequencies were determined based on facility production operations, wastewater treat ment operations, and the hydraulic retention times for the unit processes, ensuring that the effluent samples would be representative of facility effluent during triclosan

- impregnation operations. Additional WWTP process parameters collected during the sa mpling periods provided support that WWTPs were operating normally during sampling periods. The triclosan use pattern and WWTP characteristics for these two facilities are summarized in Table 11 . Results from the monitoring, which are summarized in Table 12 will be used to characterize discharge an d environmental exposure from the textile material preservative use. The estimated in

- stream concentrations for these specific facilities were based on the facilities’ permitted discharge flow rate and the receiving water body low

- flow condition (specific ally 7Q10 flow 10 

### ).

10 "The streamflow that occurs over 7 consecutive days and has a 10

- year rec urrence interval period, or a 1 in 10 chance of occurring in any one year. Daily stream flows in the 7Q10 range are general indi cators of prevalent

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Page 35 of 130 Table 11

— Textile Facility Characteristics During the Triclosan Monitoring Studies

Characteristic Facility # 1 Facility # 2 Notes Triclosan application pattern during study Intermittently used Constantly used

-- Number of days each facility was processing textiles in study period 15 11

Amount (lbs) of triclosan

containing formulation applied in study 327 636

--

Number of influent streams into WWTP 1 textile process WW 1 non

- contact cooling water WW (0.037 MGD) 1 remediation groundwater (0.005 MGD) 1 chemical (nutrients

dehydrated) influent to aeration lagoon 1 textile process WW 1 utility WW (0.144 MGD) 1 stormwater collection system

(0.021 MGD) 1 chemical (nutrients

60 mL/min) influent

to aeration lagoon

WWTP effluent flow rates (MGD) Min: 0.09 Avg: 0.21 Max:0.7 Min:1.04 Avg: 1.47 Max: 1.81 --

Hydraulic retention time (days) Min: 13 Avg: 43 Max: 100 Min:6 Avg: 7 Max: 10 --

Aeration lagoon (1) volume (MG) 2.25 3.8 each (two lagoons in series) Facility #2 has an equalization basin prior to flow into aeration lagoons Aeration lagoon mixed

liquor suspended solids concentration 2500 mg/L NR

Clarifier volume (MG) 0.147 each (2 parallel) 0.542 each (2 parallel) Facility #2 has a flash mixing/flocculation tank for chemical coagulation, if needed, prior to clarifier Polishing pond volume (MG) 6.5

--
Post

- aeration tank (MG)

-- 0.033382 Avg: average; MG: million gallons; MGD: million gallons per day; Max: maximum; Min: minimum; NR: not reported; WW: wastewater
(1) Biological treatment stage

.

drought conditions which normally cover large areas. 7Q10 values are also used by the State for regulating water withdrawals and discharges into streams." (USGS)

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Page 36 of 130 Table 12

— Triclosan and Methyl Triclosan Monitoring Data from Two Textile Manufacturing Facilities

Facility Triclosan Concentration

(ng/L) Methyl Triclosan

(ng/L)

Whole Effluent (1) Effluent Supernatant (2) In

- Stream (4)

Avg Max Med Avg Max Med Avg Max Max

No. 1 99 190 80 73.6 130 63 3.2 (3) 6.1 (3) ND (5) (1.8

- 1.9)

No. 2 138 180 130 88.8 110 84 33.1 43.2 ND (1.8)

(1) F ive consecutive, 24

- hour composite effluent samples collected from each facility’s WWTP effluent channel

. (2) Supernatant from sample subjected to centrifugation at 100,000 ms - 2

. (3) In

- stream wastewater concentration (IWC) factor of 3.2% (dilution ratio of 31.25) as per NPDES permit.
(4) IWC factor of 24% (dilution ratio of 4.167) as per NPDES permit. (5) Values in parentheses represent Method Detection Limits (MDLs) for the samples.



### 4.3.3 Water Quality

Triclosan is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at the a gency’s National Pesticides Cause of Impairment of Waters website (searched Febr uary 22, 2013) 11

, 12 

### . In addition, no Total Maximum Daily Loads (TMDL) have been developed for triclosan, based on information provided at the a gency’s National Pesticide TMDL web site (searched February 22, 2013) 13



### . More information on impaired water bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/

. From a preliminary examination , the d ioxins formed from triclosan in chlorinated waters (2,7

- dibenzodichloro

- p

- dioxin; 2,8

- dichloro

- p

- dioxin; 1,2,8

- a nd 2,3,7

- trichlorodioxins and 1,2,3,8

- tetrachlorodioxin)

, are not among congeners of toxicological concern (see Appendices B and F ). Dioxin congeners considered of environmental toxicological concern are listed in Table 34. Because the dioxin congeners a re not those of concern, a search of impaired waters due to dioxins of environmental concern was not performed for triclosan

.

11

. http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885
12 http://iaspub.epa.gov/waters10/attains_nation_cy.control?p_report_type=T#causes_303d
13 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant _group_name=PESTICIDES

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Page 37 of 130 4.3.4 Screening

- Level of Potential Risks to Aquatic Organisms from Pesticidal Uses of Triclosan Potentially Released to Wastewater Treat ment Plants (WWTPs)

EPA performed a screening

- level assessment using E

- FAST (USEPA 2007) to determine whether triclosan that might be released to municipal WWTPs from pesticidal in

- service uses of materials treated with triclosan would be expected to lead to potential risks to aquatic organisms downstream of WWTPs. This screening

- level assessment assumes that: (1) the entire maximum annual consumption volume of triclosan is released to WWTPs; (2) removal of triclosan during wastewater treatment would be 8 0 percent; and (3) concentrations of concern (COCs) based on effects endpoints for aquatic organisms (Table 10 and Appendix C ) that reflect the highest potential for toxicity. This screening level assessment demonstrates that even if the entire maximum an nual consumption volume of triclosan was released to municipal WWTPs over a

one

- year period, there would be no potential risks to listed and nonlisted aquatic organisms downstream of these WWTPs.

The results of this screening

- level analysis based on a hig h

- end scenario assuming 80 percent removal of triclosan during wastewater treatment and 54,000 kilograms per year of triclosan entering municipal WWTPs are as follows:

• At a COC of 0.5 ppb, which is a chronic COC representative of listed aquatic non

vascul ar plants, the COC is exceeded 17 days per year;

• At a COC of 0.7 ppb, which is a chronic COC representative of non

- listed aquatic non

vascular plants, the COC is exceeded 9 days per year;

• At a COC or 14.4 ppb, which is an acute COC representative of listed freshwater fish, the COC is exceeded for less than 1 day per year (i.e., 0.007).

COCs for other measurement endpoints in Table 10 would be higher and the corresponding number of days of exceedance would be even lower than the COCs examined in this screeni ng

level analysis. If an acute COC for a listed or nonlisted aquatic organism is exceeded on 1 day or more, then potential acute risks to aquatic organisms in the receptor group the organism represents are indicated. If a chronic COC for a listed or nonl isted aquatic organism is exceeded

on 20 days or more, then potential chronic risks to aquatic organisms in the receptor group the organisms represents are indicated. Consequently, these results demonstrate negligible potential for acute and chronic risks to aquatic organisms downstream of municipal WWTPs to which pesticidal triclosan could be released.

Note that the input value of 54,000 kilograms of triclosan per year assumed for WWTP influent volume is a vast overestimate of the amount of pesticidal triclosan that would be expected to enter a wastewater treatment plant. First, not all of the antimicrobial uses of triclosan listed in Table 5 would have the potential to come in contact with water that would eventually be released down

- the

- drain to a municipal WWTP. In addition, it is highly unlikely that 100 percent of the triclosan in all of these products would leach out of these products over a 1

- year period. The

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Page 38 of 130 value used as an in put for the wastewater treatment plant influent volume of the DtD model was 54,000 kilograms triclosan per year (Kline, 200 5 ). This estimate is based on the estimated volume consumption of triclosan reported in 2004 (i.e., 120,000 pounds). The percent re moval of triclosan during wastewater treatment was assumed to be 80 percent based on a study by Lee et al. (2003).

Concentrations of concern (COCs) for aquatic organisms that were used in this screening

- level assessment are based on measurement endpoints in Table 10 for which the toxicity of triclosan was highest. These include: (1) the NOAEC for green algae of 0.5 ug/L, which is the highest chronic toxicity value for any nonlisted aquatic species; (2) the EC 50 

### for green algae of 0.7 ug/L, which is the h ighest chronic toxicity value for any listed aquatic species; and (3) the COC of 14.4 ug/L, which is the acute COC for listed freshwater fish that is derived from the LC 50 

### of 288 ug/L determined for the fathead minnow, a representative freshwater fish spec ies. (COCs for acute toxicity for non

- listed aquatic organisms are determined by dividing the LC 50 

### by 2 and COCs for acute toxicity for listed aquatic organisms are determined by dividing the LC 50 

### by 20. COCs for chronic toxicity are based on the measure ment endpoint, which is usually a NOAEC.)



### 4.4 Effects Analysis Plan

O pen literature studies for effects data on triclosan and its major degradates will be identified through EPA’s ECOTOXicology (ECOTOX) database 14



### , which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The ECOTOX database will be searched when the risk assessment for triclosan is prepared.
E ndpoints more sensitive than those already selected will be reviewed for use in the risk

assessment

.


## 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 chronic toxicity, including assessments of carcinogenicity, neurotoxicit y, 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 maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As par t of its 2008 reregistration decision for triclosan , 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), triclosan is subj ect to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

14 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.

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Page 39 of 130 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 scr eening 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 ho rmonal 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 subs tance, and establish a dose

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

Under FFDCA section 408(p), the a gency 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. A second list of chemicals identified for EDSP screening was published on June 14, 2013 15 

### and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the list of chemicals, future lists, the test guid elines and the Tier 1 screening battery, please visit our website 16



### .


## 6 Next Steps

EPA will issue a DCI to all registrants of triclosan products requiring submission of the anticipated data listed under the “ Anticipated Data Needs” section of this document. Th e a gency expects to issue the DCI by March 201 5

. The a gency will conduct the human health and

e nvironmental fate and ecological hazard assessments necessary to determine whether products that contain triclosan continue to meet the FIFRA standard for registration

.



## 7 References

Ellis DD et al ; Arch Environ Contam Toxicol 11: 373

- 82 (1982)

. Environmental Protection Agency. High Production Volume Inf ormation System (HPVIS). http://www.epa.gov/hpvis/

Lee, H.B., K. Sarafin, T.E. Peart, and M.L. Svoboda. 2003. Acidic Pharmaceuticals in Sewage

— Methodology, Stability Test, Occurrence, and Removal from Ontario Samples. Water Qual. Res. J., Canada (38(4): 667

- 682.

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.
16 http://www.epa.gov/endo/

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Page 40 of 130 Miller et al ; Estogenic Activity of Phenolic Additives Determined by an In Vitro Yeast Bioass ay, Environmental Health Perspectives, Volume 109, Number 2, pp. 133

- 138, February. 2001

. Proia, L., S. Morin, M. Peipoch, A.M. Romani, and S. Sabater. 2011. Resistance and recovery of river biofilms receiving short pulses of triclosan and diuron. Sci. Total Environ. 409(17): 3129

- 3137.

Routledge and Sumpter; Structural Features of Alkylphenolic Chemicals Associated with Estrogenic Activity, Journal of Biological Chemistry, Volume 272, Issue 6, pp 3280

- 3288, February 7, 1997.

Soto, AM et al : The E

- Screen Assay as a Tool to Identify Estrogen

- An Update on Estrogenic Environmental Pollutants, Environmental Health Perspectives, Vol. 103, Supplement 7,
pp 113

- 122, October 1995

Tollefsen et al ; Estrogenicity of Alkylphenols and Alkylated Non

- Phenolics in a Rainbow Trout ( Oncorhynchus mykiss ) Primary Hepatocyte Culture. Ecotoxicology and Environmental Safety 71, pp 370

- 383, 2008

.

U nited States Environmental Protection Agency (U SEPA ). 2007. Exposure and Fate Assessment Screening Tool (E

- FAST), http://www.epa.gov/opptintr/exposure/pubs/efast.htm

. United States Food & Drug Administration (FDA). 2008. Nomination Profile T riclosan [CAS 3380

- 34

- 5] Supporting Information for the Toxicological Evaluation by the National Toxicology Program. July 2008.

Yamasaki et al ; Immature Rat Uterotrophic Assay of 18 Chemicals and Hershberger Assay of 30 Chemicals. Toxicology 183, pp 93

- 1 15, 2003

.

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# APPENDIX A : T oxicology Profile

Hazard/Toxicity

Acute Toxicity for Product Labeling

A complete database of acute toxicity data for triclosan was available to the a gency at the time the RED was written. A summary of the findings, which are detailed in the RED, is included below in Table 13. Acute toxicity studies in experimental animals with technical grade triclosan show that by the oral and dermal routes, triclosan is of low acute toxicity (Toxicity Category IV; MRIDs 43206501 and 9 4044). By the inhalation route of exposure, triclosan was assigned Toxicity Category II for acute exposures and is thus of higher acute toxicity by inhalation exposure than by oral or dermal exposures (MRID 42306902 and 43310501). Triclosan produces mode rate irritation to the eyes (MRID 94045) and skin (MRID 42306903) with a Toxicity Category III assigned for both for acute exposures. Triclosan was not a dermal sensitizer in guinea pigs using the Buehler method (MRID 43206502).

Table 13

- Acute Toxicity Profile for Triclosan

Guideline Number Study Type/ Test substance (% ai ) MRID Number/ Citation Results Toxicity Category 870.1100

(§81

- 1) Acute Oral

- Rat Triclosan (99.7% ai ) 43206901 LD 50 

### : >5000 mg/kg IV

870.1200

(§81

- 2) Acute Dermal

- Rabbit Triclosan (97% ai ) 94044 LD 50 

### : >9300 mg/kg IV

870.1300

(§81

- 3) Acute Inhalation

- Rat Triclosan (100.5% a.i.) 42306902, 43310501 LC 50 

### : >0.15 mg/L II

870.2400

(§81

- 4) Primary Eye Irritation

Rabbit Triclosan (97% ai ) 94045 moderately irritating II

870.2500

(§81

- 5) Primary Dermal Irritation

Rabbit Triclosan (% ai not provided) 42306903 PII: 3.5 at 72 hours III

870.2600

(§81

- 6) Dermal Sensitization

Guinea Pig Triclosan (99.7% ai ) 43206502 Not a Sensitizer NA

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### Non

- Acute Toxicity

The toxicology database for the triclosan registration review case is comprised principally of studies that were available to the a gency when the RED was written in 2008. Additional published research on triclosan completed after 2008 is also included in the table below

. These data were included as part of the background materials for the 2011 SAP meeting. The toxicology database for triclosan is large. The non

- acute toxicology studies comprising the database are summarized in tabular format in this scoping document. Full summaries of these studies can be found in the Toxicology Disciplinary Chapter in support of the RED in regulations.gov in docket n umber EPA

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Table 14

- Non

- Acute Toxicity Studies for Tr iclosan

Guideline Number/ Study Type/ Test Substance (% ai ) MRID Number (Year)/ Citation/ Classification/ Doses Results

870.3100 (§82

- 1) 90

- day Oral

– Rat Triclosan Purity: Not Reported 133545 Acceptable/Guideline 0, 1000, 3000, and 6000 ppm NOAEL: 1000 ppm The test compound caused nonspecific dose

- related liver toxicity at 3000 and 6000
ppm

870.3100 (§82

- 1) 90

- day Oral

– Rat Triclosan Purity: 99.7% 43022605 Acceptable/Guideline 0, 25, 75, 200, 350, 750, and 900 mg/kg/day LOAEL = 25 mg/kg/day based on the changes in clinical chemistry and hematology parameters as well as lesions in the liver.

NOAEL = Not Determined

870.3100 (§82

- 1) 28

- day Oral

- Mouse Triclosan Purity: >99% 44389707 Acceptable

- Guideline 0, 6.48, and 135.59 mg/kg/day (M), 0, 8.25, and 168.78 mg/kg/day (F) LOAEL (M): 135.59 mg/kg/day LOAEL (F): 168.78 mg/kg/day based on biochemical and morphological effects on the liver. NOAEL(M): 6.48 mg/kg/day NOAEL (F): 8.25 mg/kg/day 870.3150 (§82

- 1) Oral Subchronic (non

rodent) Triclosan Purity: Not Reported 96102 Acceptable

- Guideline 0, 12.5, 25, 50, and 100 mg/kg/day NOAEL: 12.5 mg/kg/day LOAEL: 25 mg/kg/day based on histopathologic changes in the liver of treated dogs 870.3250 (§82

- 2) 90

- day Dermal

- Rat Triclosa n Purity: 99.7% 43328001 Acceptable/Guideline 0, 10, 40, or 80 mg/kg/day NOAEL: 40 mg/kg/day (excluding dermal findings) LOAEL: 80 mg/kg/day Non

- guideline 14

- day Repeated Dose

Dermal Toxicity

– Mouse Triclosan Purity: 99.3% 44389708 Acceptable

- Non

- Guideline

0, 0.3, 0.6, 1.5, 3.0, or 6.0 mg/animal/day LOAEL: 1.5 mg/animal/day based on
treatment

- related dermal irritation at the treatment site and on increased liver weights in this treatment group. NOAEL: 0.6 mg/animal/day Non

- guideline 14

- day Repeated Dose Dermal Toxicity

– Rat Triclosan Purity: 99.3% 44389710 Acceptable

- Non

- Guideline

0, 0.3, 0.6, 1.5, 3.0, or 6.0 mg/animal/day LOAEL: 6.0 mg/animal/day based on
treatment

- related dermal irritation at the treatment site NOA EL: 3.0 mg/animal/day

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870.3700a (§83

- 3) Developmental

– Rat (oral) Triclosan Purity: 99.8% 43817502, 43717503 Acceptable

- Guideline 30, 100, or 300 mg/kg/day Maternal: LOAEL: 300 mg/kg/day NOAEL: 100 mg/kg/day At 300 mg/kg/day, transient diarrhea, retarded body weight gain during the period of treatment, and reduced food consumption and increased water consumption from the onset of treatment, throughout the gestation period.

Developmental: LOAEL: Not Determin ed (> 300 mg/kg/day) NOAEL: > 300 mg/kg/day No evidence of pre

- or postnatal developmental toxicity

870.3700a (§83

- 3) Developmental

- Rabbit (oral) Triclosan Purity: 99.8% 43820401, 43022607 Acceptable /

- Guideline 15, 50, or 150 mg/kg/day Maternal: LOAEL: 150 mg/kg/day NOAEL: 50 mg/kg/day

Developmental: LOAEL: Not Determined (>150 mg/kg/day) NOAEL: ≥ 150 mg/kg/day

870.3800 (§83

- 3) Reproduction

- Rat (oral) Triclosan Purity: ≥99% 40623701 Acceptable 0, 300, 1000, and 3000 ppm (0, 15, 50, and 150 mg/kg/day) Reproductive: NOAEL: 50 mg/kg/day LOAEL: 150 mg/kg/day for decreased viability

Systemic /Parental: NOAEL: 50 mg/kg/day LOAEL: 150 mg/kg/day for a decrease in body weights and food consumption at various points during premating, gestation, and lactation for both F0 and F1 parents

Developmental: NOAEL: 50 mg/kg/day LOAEL: 150 mg/kg/day for decreased body weight and increased mortality 870.4300 (§83

- 3) Chronic Toxicity

-

Baboon (oral) Triclosan Purity: Not Reported 133230 Acceptable/Guideline 30, 100, and 300 mg/kg/day NOAEL: 30 mg/kg/day LOAEL: 100 mg/kg/day based on clinical signs of toxicity.

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870.4300 (§83

- 3) Chronic/Carcinogenicity

– Rat Triclosan Purity: 99% 42027906 Minimum 2

- year study: 0, 300, 1000, or 3000 ppm (0, 15.3, 52.4, and 168.0 mg/kg/day in males; 0, 20.0, 66.9, and 217.4 mg/kg/day in females) 52 week study: 6000 ppm. Systemic Toxicity: NOAEL: 52.4 mg/kg/day based on the increase in non

- neoplastic liver pathology observed in male rats at the 168.0 mg/kg/ day dose.

LOAEL: 168.0 mg/kg/day based on the histopathological incidence of hepatic necrosis

No evidence of carcinogenicity in this study

870.4200 (§83

- 3) Carcinogenicity

Mouse Triclosan Purity: 99% See, Norman A. (1996) FDA Review 0, 10, 30, 100, or 200 mg/kg/day NOAEL: 10 mg/kg/day in regard to tumorigenicity (and all other effects with the exception of reduced plasma cholesterol)

Increased incidence of liver neoplasms at 30 mg/kg/day and above.

870.4300 (§83

- 3) Chronic/Carcinogenicity

– Hamster Tr iclosan Purity: 99.5% 44874001, 44751101 Acceptable/Guideline 0, 12.5, 75, and 250 mg/kg/day NOAEL: 75 mg/kg/day LOAEL: 250 mg/kg/day based on increased mortality (males), nephropathy, histopathologic findings in the stomach and testes and general clinical condition deterioration

- lethargy, hunched posture, pallor, thin appearance, unsteady gait

No evidence of carcinogenicity in this study

870.5100 (§84

- 2) Bacterial Reverse

Mutation Test Triclosan Purity: ≥99% 43533301 Acceptable/Guideline 0.015, 0.050, 0.15, 0.5, or 1.5 ug/plate Negative

Triclosan was cytotoxic at 1.5 ug/plate without S9 and at doses of ≥ 0.5 ug/plate with S9. No mutagenic response was seen at any dose levels with or without S9.

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870.5100 (§84

- 2) / Bacterial Reverse

Mutation Test / Triclosan Purity: 100.5% 44389705 Acceptable/Guideline TA100 and TA1538 were exposed to 0.005

- 5,000 ug/plate (

- S9) and 0.005

- 50 ug/plate (±S9). Strains TA98, TA100, TA1535, TA1537, and TA2538, were evaluated for

mutagenicity at 0.05

- 5.0

u g/plate (+S9) and all except

TA100 at 0.00167

- 0.167 ug/plate (

- S9). Without S9,

TA100 was evaluated for mutagenicity at 0.00167

- 0.167 ug/plate. Negative

There were no reproducible, dose

- related differences in the number of revertant colonies in any tes ter strain at any dose level/condition compared to the vehicle controls.

870.5300 (§84

- 2) / In Vitro Mammalian Cell Gene Mutation Test / Triclosan Purity: > 99% 44389704 Acceptable/Guideline 1 to 25 ug/ml (

- S9) and from 1 to 20 ug/mL (+S9) Negative

Triclosan was negative for inducing forward mutations at the TK locus in mouse L5178Y cells both with and without metabolic activation. 870.5375 (§84

- 2) / In Vitro Mammalian Chromosome Aberration Test / Triclosan Purity: > 99% 47276601 Acceptable/Guideline 0 (DMSO), 0.1, 0.3, 0.5, and 1.0 ug/ml (+S9) and 0, 4.8, 9.5, 19, 30, and 38 ug/ml (

- S9) Negative

There was no treatment

- related increase in clastogenicity at any dose.

870.5375 (§84

- 2) / In Vitro Mammalian Chromosome Aberration Test / Triclosan Purity: 99%

- 100% 43740801 Acceptable/Guideline Nonactivated doses of 1 ug/mL (7

- hour cell harvest), 0.1

- 3 ug/ml (18

- hour harvest), or 3 ug/ml (28

- hour harvest) and S9

-

activated concentrations of 3

ug/ml (7

- and 28

- hour cell harvests) or 0.1

- 3 ug/ml (18

- hour harvest). Positive

Nonactivated FAT 80’023/Q at 1 and 3 ug/mL (18

- hour harvest) induced a dose

related increase in the yield of cells with abnormal chromosome morphology. The response was significant (p ≤ 0.001) at the higher concentration. A significant increase (p ≤ 0.001 was also seen at 3 ug/ml (28

- hour harvest). The most frequently observed type of chromosome damage was exchange figures. In the presence of S9 activation, nonsignificant but conce ntration dependent increases in cells bearing exchange figures were also seen at 1 and 3 ug/ml (18

- hour harvest). The data are, therefore, sufficient to conclude that FAT 80’023/Q is active in this test system.

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870.5385 / Mammalian Bone Marrow Chromosomal Aberration Test / Triclosan Purity: 99%

- 100% 43740802 Acceptable/Guideline 4000 mg/kg Negative

No signs of overt toxicity or cytotoxicity effects on the target organ were seen in any treatment group. There was also no indication of a clastogenic effe ct at any sacrifice time. 870.5550 / Unscheduled DNA Synthesis in Mammalian Cells in Culture / Triclosan Purity: 100.5% ai 47276602 Acceptable/Guideline 0.25, 0.5, 1.0, and 2.5 μg/mL Negative

There was no UDS in cultured rat hepatocytes at the concentrations tested. The positive controls functioned as expected.

870.7485 / General Metabolism Hamster / Triclosan Purity: 99% ai 45307501, 45307502 Acceptable/Guideline 2 or 200 mg/kg After single or repeated oral doses of 2.0 or 200 mg/kg 14 C

- triclosan, urine was the major route of elimination for triclosan radioactivity (60

- 80% of the administered radioactivity). Fecal elimination represented from 12

- 35% of administered radioactivity across the oral dose groups. Compared to the low dose, a dministration of a single high or repeated dose resulted in a shift toward urinary elimination and a decrease in fecal elimination.

Peak plasma and blood concentrations of triclosan

- derived radioactivity occurred at one hour post

- dose for both the low and high oral doses. Concentration in plasma appeared higher than in whole blood at each sampling time. There did not appear to be any significant sex differences in blood or plasma kinetics at the low or high dose.

The major urinary metabolite detected after oral administration was the glucuronide conjugate of triclosan. The major fecal metabolite was parent triclosan in all oral dose groups (1

- 8). After intravenous administration, triclosan glucuronide was also detected as the major urinary metabolite . Tissue metabolite analysis showed that the glucuronide and sulfate conjugates of triclosan were the major metabolites detected at the low and high oral single doses.

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870.7485 / General Metabolism Mouse / Triclosan Purity: 99% ai 45307503 Acceptable/Guideline 2 or 200 mg/kg The test material was rapidly absorbed following oral administration, and was eliminated primarily through the feces, via biliary excretion. Urinary excretion was secondary to that in the gastrointestinal tract. This e xcretory pattern was consistent following I.V. administration as well. Primary excreted compounds in the urine following single oral exposures included the unmetabolized parent compound and two parent conjugates (parent sulfate and parent glucuronide); fe cal excretion was primarily that of the free parent compound, as small amounts of glucuronide were detected, and no sulfate was detected

870.7485 / Metabolism/Kinetics

Multiple species / Triclosan purity: 99.5% 149464 Acceptable Intravenous, intraduodenal, or gavage at 10 mg/kg (mice), 0.4

mg/kg (rats), 5 mg/kg (rats, rabbits, dogs), or 50 mg/kg (rabbits). Absorption in rats calculated between 70

- 80%. Data not generated for other species for absorption. Peak blood levels occurre d within 30 minutes in rats following a single oral or intravenous dose of 5 mg/kg and at 2

- 4 hours for dogs. Based upon data from rats, tissue burdens declined appreciably over 24 hours with no indication of accumulation/sequestration. Urinary excretion accounted for 3

- 17% of the administered oral dose in rats over a 168

- hour period, and 8.3

- 8.8% in dogs over a 120

- hour period. Urinary elimination in dogs was somewhat greater following intravenous administration; 12.9

- 17.7% over 120 hours. For rabbits, urinary excretion was a significant route of elimination and accounted for 74.1% of a single 50 mg/kg oral dose and 60.4% of a single 5 mg/kg oral dose over a 72

- hour period. The biliary secretion data in rats showed that most of the fecal radioactivity

c ould be attributed to biliary elimination products rather than unabsorbed test material. Metabolite data in rats revealed glucuronide conjugates and unchanged parent compound as biliary metabolites.

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870.7485 / Metabolism/Kinetics Rats, Dogs, Baboons, Mice / 68161 Unacceptable
14 C

- triclosan (>98% radiochemical purity, lot/batch no. not specified) was administered to male rats by gavage at doses of 5 or 30 mg/kg (single or 14

- day repeated). In addition, two male beagle dogs and two male baboons received single 5 mg/kg doses in gelatin capsules and 10 male mice were given a single 10 mg/kg intravenous dose. Peak concentrations in rats were attained within three hours after a single oral dose of 5 mg/kg and the concentrations declined approximately five

- fo ld within 24 hours. For dogs, somewhat greater blood t max values were observed but were variable (2

- 8 hours) for the two dogs tested. Time

course analysis of tissues from mice given a single intravenous dose (10 mg/kg) of 14 C

triclosan showed that the highest concentrations of radioactivity were initially associated with highly perfused organs/tissues. These levels significantly declined within 30 minutes but the decline was somewhat less rapid for organs /tissues associated with metabolism and elimina tion and notably increased for the gall bladder. For monkeys, urinary excretion accounted for 56.69% of the administered dose and fecal elimination accounted for 25.15%. For dogs, urinary and fecal elimination accounted for 12.16% and 68.30%, respectively , of the administered dose. In both species, most of the urinary and fecal excretion occurred within 48 hours.

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870.7485 / Metabolism/Kinetics Rats / 47261405 Acceptable
14 C

- labeled triclosan (99% ai

, Batch # B

- 71.32A) was administered to two groups of 10 Wistar rats/dose and four groups of 36 Wistar rats/dose. Groups 1 and 2 were administered a single dose of 2.3 mg/kg or 211 mg/kg of radiolabeled triclosan, respectively, by gavage and sacrificed at 96 hours. Groups 3 and 4 were administered a single dose of 2.2 mg/kg or 199 mg/kg of radiolabeled triclosan, respectively, by gavage and groups of 4 rats were sacrificed at 0.5, 1, 2, 4, 8, 24, 48, 72, or 96 hours. Groups 5 and 6 were administered thirteen doses of 2.0 mg/kg or 201 mg/kg of non

radiolabeled tri closan, respectively, through food followed by a single gavage dose of radiolabeled triclosan. Fecal excretion predominated at both dose levels and dosing regimes. Urine accounted for 10

- 11% of the administered dose, and feces 70

- 80% of the administered d ose. Half lives for triclosan and its equivalents in the plasma ranged from 10.0

- 12.6 hours, single (12.6 or 10 hours, low

- or high

- dose, respectively) and repeated (11.7 or 10.7 hours, low

- or high

- dose, respectively) dose groups were comparable.

Repeat ed doses of triclosan did not cause significant changes to the pharmacokinetics of triclosan and/or its metabolites in the rat, as compared to single dose administration. In addition, the results indicate that triclosan exhibits saturation of absorption an d a higher conjugating/metabolizing capacity at approximately 200 mg/kg, as compared to approximately 2 mg/kg.

870.7485 / Metabolite Identification Dogs/Baboons / 79590 Acceptable/non

- guideline Two baboons and two dogs were administered a single oral dose (5 mg/kg) of [ 14 C]

- GP 41 353 (radiochemical purity 99%; chemical purity 99.5%; batch/lot nos. not provided) In the dog, glucuronide conjugates accounted for 7% of blood radioactivity and sulfate conjugates accounted for 88% of radioactivity sampled at thre e hours. At six hours, ~86% of radioactivity in the blood was associated with glucuronide/sulfate conjugates. For the baboon, glucuronide conjugates represented about 25% and sulfate conjugates represented about 33% of radioactivity at 8 hours postdosin g. Similar analysis with blood collected at 12 hours postdosing revealed somewhat greater amounts of sulfate conjugates (~88%). For the baboon, analysis of 0

- 72 hour urine samples revealed that approximately 6% of the urinary radioactivity was due to

unc hanged triclosan. Up to 75% of the urinary radioactivity underwent spontaneous hydrolysis presumably due to endogenous urinary β

- glucuronidase.

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870.7600 / Dermal Absorption R abbit / Triclosan Concentration: 3% 34335 Acceptable/Guideline 48% of the applied dermal dose was absorbed

Liver Biochemical Induction

– Mouse (oral)

Triclosan Purity: Not Reported 44389702 Acceptable/non

- guideline 0, 25, 75, 350, and 900 mg/kg bw for M and 0, 25, 350, and 900 mg/kg bw for F The test article is a strong, but reversible barbiturate

- type and peroxisome proliferator

- type inducer of foreign compound metabolizing enzymes in male and female mice

Liver Biochemical

Induction

– Rat / Triclosan Purity: Not Reported 44389703 Acceptable/non

- guideline 0, 300, 1500, and 6000 ppm Food consumption was reduced in all test groups with the exception of the 6000 ppm dose group which had a reduced food intake on day 1 and then an almost 3

- fold increase over the control group. Group mean body weight was not significantly changed exce pt in the 6000 ppm group which was slightly decreased (4

- 8%) over the first 8 days of the study. At the end of the study, rats receiving 6000 ppm showed a significant increased absolute and relative liver weight.

Significant effects were observed for

seve ral biochemical parameters in the liver at the 6000 ppm dose level. Cytochrome P

450 content was approximately doubled in the high dose group, while activity of glutathione

- S

- transferase was increased by 65%. Other enzymes affected at the 6000 ppm dose lev el included an increase in lauric acid hydroxylation and an increase in PROD and EROD activity. In general, those animals allowed to recover for 28 days following the 14

- day administration of test chemical showed no significant induction or inhibition of e nzyme activities.

Liver Biochemical Induction

– Hamster / Triclosan Purity: 99.5% 44389706 Acceptable/Non

- Guideline 0, 700, 5,000, and 15,000 ppm [approximately 0, 49.9, 309.8, 799.0 mg/kg/day (M) and 46, 314.3, and 958.8 mg/kg/day (F)] or 0 or 15000 ppm (recovery groups) Systemic Toxicity NOEL: 700 ppm LOEL: 5000 ppm based on induction of total cytochrome P

- 450, EROD, and PROD in male and female hamsters, and induction of Mab clo4 immunoreactive protein (CYP4A peroxisome proliferators inducible P

- 450) in male hamsters.

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Liver Cell Proliferation

– Mouse / Triclosan Purity: Not Reported 44389701 Acceptable/Guideline 0, 25, 75, 200, 350, or 900 mg/kg/day NOAEL(M): 25 mg/kg/day NOAEL(F): 75 mg/kg/day

Liver Cell Proliferation

– Mouse / Triclosan Purity: Not Reported Eldridge, 1995 44389701 Acceptable/Guideline 0, 25, 75, 200, 350, 750, or 900 mg/kg/day An increase in the labeling index was apparent at 200 mg/kg/day and above for male and female mice. The labeling index was increased at day 45 in both sexes at 350 and 900 mg/kg/day, and as noted, this continued at these dose levels at 90 days as well as t he increase observed at 200 mg/kg/day at 90 days for both sexes. The observation of an increase in labeling index from this study, in conjunction with other data which show toxicity to the liver of rats and mice, indicate cytolethality of triclosan which i s followed by induced cellular regeneration. However, there may be species differences in the response to triclosan hepatotoxicity.

In the report, it was noted that the mode by which a chemical induces cell proliferation is an important consideration. In the case of triclosan, the evidence suggests a hepatotoxic effect followed by regenerative cell turnover, in contrast to agents which act as direct mitogens. For chemicals producing increased cell turnover through cytolethality, a threshold can be inferre d below which these effects would not occur. This scenario could apply to triclosan based on the available data.



### Other Toxicological Effects

In addition to the effects of triclosan related to cellular proliferation (summarized in the table above), triclo san has also been shown to have effects on the mammalian endocrine system. The studies conducted on these effects are summarized below.

Anti

- estrogenic/Androgenic Effects

Gee et al . (2007) reported displacement of 3 

### H

- estradiol from the estrogen receptor of human MCF7 breast cancer cells by triclosan and inhibition of the estrogen

- responsive ERE

- CAT reporter gene by triclosan at 10 - 5 

### M in the presence of 10 - 10 

### M estradiol. Triclosan was also

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Page 52 of 130 shown to have anti

- androg enic activity in this study as shown by displacement of 3 

### H

- testosterone from the rat androgen receptor, although a 1000

- fold molar excess of triclosan was needed to produce a 49% displacement of testosterone. Using a mouse mammary tumor cell line with a

st ably

- transfected androgen reporter gene (LTR

- CAT), induction of CAT activity by testosterone was inhibited in the presence of triclosan at 10 - 5 

### M and above. The proliferative response of these mouse mammary tumor cells to testosterone was also inhibited by triclosan.

Ahn et al . (2008) examined the biological activity of triclosan in in vitro , cell

- based, and nuclear receptor

- responsive bioassays for the aryl hydrocarbon (Ah), estrogen (E), and androgen (A) receptors. As reported in the study, triclosan at a concentration of 10 μM induced luciferase expression to 40% of that seen with 2,3,7,8

- tetrachloro dibenzo

- p

- dioxin (TCDD), but it inhibited the induction of luciferase expression by TCDD by approximately 30%. These agonist/antagonist results are consiste nt with TCS being a partial agonist of the Ah receptor. In both the ER

- and AR

- responsive bioassays, triclosan exhibited antagonistic activity in this study.

Chen et al . (2007) examined the anti

- androgenic potential of triclosan using a cell

- based stably transfected cell line lacking critical steroid metabolizing enzymes. Triclosan alone exhibited no androgenic activity at concentrations up to 10 μ M, but transcriptional activity in the presence of 0.125 nM testosterone was inhibited by 10 μ M triclosan by 9 2%, and by 38.8% at 1.0 μ M triclosan.

Estrogenic Effects

Tamura et al . (2006) studied the androgen receptor (AR) activity of listed chemicals, so called SPEED 98, by the M inistry of the Environment, Japan, and structurally related chemicals was character ized using MDA

- kb2 human breast cancer cells stably expressing an androgen responsive luciferase reporter gene, MMTV

- luc. Based on results generated above suggesting that chemicals with diverse structures were capable of disrupting the endocrine systems me diated by AR, a comparative molecular field analysis (C0MFA) model was developed to analyze the structural requirements necessary to disrupt AR function. Triclosan had AR antagonist activity with an IC50 value of 7.5 μM, which was as potent as linuron base d on in vitro MDA

- kb2 reporter gene assay.

Stoker et al . (2010) examined the potential estrogenic effects of triclosan using the rat weanling uterotrophic assay, an assay for detection of uterine growth in response to estrogen agonists. No changes in mean wet or blotted uterine weight were observed following dosing with triclosan alone for three days (1.18 to 300 mg/kg triclosan). However, there was a significant dose

dependent increase in the mean uterine wet and blotted weight in the cotreated groups who received 4.69 to 37.5 mg/kg triclosan plus 3 ug/kg ethinyl estradiol for three days. The data from the uterotrophic assay showed that triclosan enhanced the uterine response to ethinyl estradiol. Triclosan appeared to stimulate this estrogen dependent res ponse by enhancing the activity of exogenously administered estrogen and not by a direct stimulation of the estrogen receptor, as

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Page 53 of 130 triclosan doses as high as 300 mg/kg without cotreatment with EE did not alter uterine weight or histology.

Effects on Thyro id

Recent in vivo data from rats provides evidence that triclosan alters thyroid hormone homeostasis. Crofton et al (2007) demonstrated that short

- term (4

- day) oral exposure to triclosan decreased serum total T4 concentrations and increased liver weights . Using a benchmark response of 20%, the benchmark dose (BMD) and lower bound (BMDL) for T4 were 69.7 and 35.6 mg/kg/day, respectively. This study discussed the possibility of more than one mechanism involved in the decrease of T4 levels after oral exposu re to triclosan, including activation of the human pregnane X receptor (PXR; Jacobs et al ., 2005) resulting in increases in sulfonation or glucuronidation activity.

The effect of triclosan on thyroid has also been investigated using the pubertal assay (US EPA, 2008). Weanling male rats were dosed by oral gavage for 30 days starting on postnatal day 23 with 0, 3, 30, 100, 200 or 300 mg/kg/day of triclosan. Triclosan did not alter pubertal development, reproductive tract development or gonadal histopathology, T4 concentrations decreased by 47.4, 49.8, 80, and 81% at 30, 100, 200, and 300 mg/kg respectively. Triiodothyronine (T3) was only significantly decreased at 200 mg/kg, while thyroid stimulating hormone (TSH) levels were unaffected at any dose level. Thyr oid histology was also not altered at 100 and 200 mg/kg. Histology at 300 mg/kg is currently under examination. Mean liver weight of dosed male rats was increased significantly at the 100 mg/kg dose and above, suggestive of hepatic enzyme induction and in creased clearance of thyroid hormone

. Using a BMR of 20% and the BMD was calculated as 14.51 mg/kg with a benchmark dose limit (BMDL) of 7.23.

The mechanism of action for the decrease in T4 levels observed in juvenile rats in this study was not investigat ed. Mean liver weight of dosed male rats was increased significantly at the 100 mg/kg dose and above, suggestive of hepatic enzyme induction and increased clearance of thyroid hormone. However, the study noted no induction of liver UDP

- glucuronyl transfera se at the 3 or 30 mg/kg dose levels. In a shorter term study in which weanling female Long

- Evans rats were exposed by oral gavage for 4 consecutive days to triclosan at 0, 10, 30, 100, 300, or 1000 mg/kg (Crofton et al ., 2007), significant decreases in serum T4 concentrations were observed at 100 mg/kg and above in a dose

- related manner. This study discussed the possibility of more than one mechanism involved in the decrease of T4 levels after oral exposure to triclosan , including activation of the human pregnane X receptor (PXR; Jacobs et al ., 2005) resulting in increases in sulfonation or glucuronidation activity. Further research is needed in this area.

While there are some uncertainties with respect to the pharmacod ynamics of triclosan, the pharmacokinetics of triclosan, which has been studied in several animal species and in humans, shows similar half

- life of elimination in experimental animal species studied (rat, hamster,

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Page 54 of 130 mouse) in comparison to humans. It has be en observed, however, that enterohepatic circulation of triclosan occurs in the rat, and that a significant first

- pass effect occurs in humans. Comparison of comparable oral doses administered to rats and humans shows smaller area under the curve (AUC) val ues for humans compared to rats, suggesting less overall systemic exposure. In addition, it is also known that the rat is a more sensitive species than the human with respect to perturbations in thyroid homeostasis, based on the shorter half

- life of T4 i n the rat (12

- 24 hours) compared to humans (5

- 9 days), and the lack of the high affinity binding protein thyroxine binding globulin in rats (Capen, 1996).

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Page 55 of 130 REFERENCES TOXICOLOGY DATA

MRID 34335: Stierlin, H. (1968) “Percutaneous Absorption of GP 41 353 in the Rat and the Rabbit.” (Unpublished study; prepared by J.R. Geigy, AG, submitted by Ciba

- Geigy Corp., Greens

- boro, N.C.; CDL:000506

- M)

MRID 43429: Stenger, E.G.; Scharer, (1963) “Local Effects on Rabbit's Eye.” (Unpublished study; prepare d by J.R. Geigy, AG, Switzerland, submitted by Ciba

- Geigy Corp., Greensboro, N.C.; CDL:108210

- J)

MRID 96102: Burther, B.R.; Gordon, D.E. (1973) “Report to Ciba

- Geigy Corporation: 90

- day Subacute Oral Toxicity Study with Irgasan DP

- 300 in Beagle Dogs: I BT No. C1435.” (Unpublished study; prepared by Industrial Bio

- Test Laboratories, Inc., submitted by Ciba

- Geigy Corp., Greensboro, N.C.; CDL:008400

- C)

MRID 100178/130187: Schoenig, G. (1967) “Report to Geigy Chemical Company: Acute Dermal Toxicity Study on CH 3565: IBT No. A5460.” (Unpublished study; prepared by Industrial Bio

- Test Laboratories, Inc., submitted by Ciba

- Geigy Corp., Greensboro, N.C.; CDL:000503

- D)

MRID 133545: Goldsmith, L. (1983) 90

- Day Oral Toxicity Study in Rats with Fat 80’023/H: LBI Project No. 22188. Final Report. (Unpublished study received Dec. 23, 1983 under 100

- 502; submitted by Ciba

- Geigy Corp.)

MRID 251773: Drake, J.C. & Buxtorf, A. (1976) 1 Year Oral Toxicity Study in Baboons with Compound FAT 80 023/A. Geigy Pharmaceu ticals, Toxicology Department.

MRID 40623701: Morseth, S.L. (1988) “Two

- Generation Reproduction Study in Rats with FAT 80’02390” Hazleton Laboratories America, Inc.

MRID 42027906: Study 1

- Yau, E.T. and Green, J.D. (1986) Fat 80’023 2 Year Oral Administration to Rats; Study 2

– Parkes, D.G. (1986) Determination of Fat 80’023 in Blood and Tissue Samples Taken During a Two

- Year Chronic Oral Toxicity/Oncogenicity Study in Albino Rats (24

- month Final Report). Ciba

- Geigy Corporation. MRID 42306902, 43310501: Duchosal F. and Ph. Thevenaz (1990) “4

- Hour Acute Inhalation Toxicity Study with FAT 80’023/Q in Rats” Ciba

- Geigy Ltd.

MRID 42306903: Sachsse, K.; Ullman, L. (1 975) Skin Irritation in the Rabbits after Single Application of FAT 80’023/A. Unpublished Study Conducted by Ciba Geigy Ltd., Basel

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Page 56 of 130 Switzerland. Project No. Siss 4719. Submitted to EPA by Chemical Division of Ciba Geigy Corp. (9/11/75).

MRID 43022605: Trutter, Janet A. (1993) “13

- Week Subchronic Oral Toxicity Study of Triclosan in CD

- 1® Mice.” Hazleton Washington, Inc. MRID 43206501: Wnorowski, Gary. (1994) “Acute Toxicity Limit Test for Triclosan (Irgasan® DP 300) Product Safety Labs.

MRID 432 06502: Wnorowski, G. (1994) Dermal Sensitization Test

- Buehler Method for Triclosan (Irgasan® DP 300) Lot No. 5.2.0211.0. Product Safety Labs; Study No. 2635. Submitted to EPA by Ciba

- Geigy Corp. Unpublished.

MRID 43328001: Trimmer, Gary W. (1994) “90

- D ay Subchronic Dermal Toxicity Study in the Rat with Satellite Group with Irgasan DP300 (MRD

- 92

- 399)” Exxon Biomedical Sciences, Inc.

MRID 43533301: Jones, E., Wilson, L.A. (1988) “Ames Metabolic Activation Test to Address the Potential Mutagenic Effect of Triclosan (Irgasan DP 300)” Huntingdon Research Center, Ltd. Cambridgeshire, England.

MRID 43740801: Heidemann, A. (1990) “Chromosome Aberration Assay in Chinese Hamster V79 Cells In Vitro with FAT 80’023/Q (Irgasan® DP 300); Cytotest Cell Research GM BH & Co. KG, Federal Republic of Germany; Study No. 179100. Unpublished. MRID 43740802: Volkner, W. (1991) “Chromosome Aberration Assay in Bone Marrow Cells of the Rat with FAT 80’023/Q (Irgasan® DP300); Cytotest Cell Research GMBH & Co. KG, Federal Rep ublic of Germany; Study No. 218305. Unpublished.

MRID 43817502, 43817503: Denning, H.J., Sliwa, S., and Willson, G.A. (1992) “Triclosan: Effects on Pregnancy and Post

- Natal Development in Rats: Volume 1, Volume 2 and Appendices 1

- 17” Unilever Research, Colworth/ Welwyn Lab. MRID 43820401, 43022607: Schroeder, R.E. et al. (1992) “A Segment II Teratology Study in Rabbits with Irgacare MP” Bio/dynamics Inc.

MRID 44389701: Eldrige, S. (1993) Cell Proliferation in Rodent Liver: (Triclosan): Final Report: Lab Project Number: 142. Unpublished study prepared by Pathology Associates, Inc. 14

p.

MRID 44389702: Molitor, E., Persohn, E., Thomas, H. “The Effect of FAT 80’023/Q (Irgasan DP 300) on Selected Biochemical Liver Parameters Following Subchronic Dietar y Administration to Male and Female Mice. Ciba

- Geigy Limited, Switzerland, Report CB 91/18, May 22, 1992.

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Page 57 of 130 MRID 44389703: Molitor, E.; Persohn, E. (1993) The Effects of FAT 80’023/Q (Irgasan DP 300) on Selected Biochemical and Morphological Liver Param eters Following Dietary Administration to Male Rats: Lab Project Number: CB 92/28. Unpublished study prepared by Ciba

- Geigy Ltd. 70p.

MRID 44389704: Henderson, L.M., et al. (1988) An Assessment of the Mutagenic Potential of Triclosan Using the Mouse Lymphoma TK Locus Assay. Huntingdon Research Center Ltd., Huntingdon, Cambridgeshire, PE18 6ES, England. Study No. ULR 216/88644. Unpublished.

MRID 44389705: Stankowski, L.F., Jr. et al. (1993) Amended Final Report, Ames/Salmonella Plate Incorporation Assay on Test Article 39316 (CC #14663

- 09). Pharmakon USA, P.O. Box 609, Waverly, PA. Laboratory Study Report No. PH 301

- CP

- 001

- 93. Unpublished.

MRID 44389706: Thomas, Rer. Nat. H. (1994 ) The Effect of FAT 80’023/Q and the Model Inducers Phenobarbitone, 3

- Methylcholanthrene, Pregnenolone 16 ∞

- carbonitrile and Nafenopin on Selected Biochemical and Morphological Liver Parameters in the Syrian Hamster. Study conducted by Ciba

- Geigy Limited . Study number CB 93/40. Unpublished.

MRID 44389707: Thevenaz, Dr. Phil. (1987) Final Report: FAT 80023: 28

- Day Toxicity Study in Mice (Administration in Feed) with Special Reference to Histopathology. Ciba

- Geigy Ltd., Basle, Switzerland. Unpublished.

MRID 44389708: Burns, J.M. (1997) 14

- Day Repeated Dose Dermal Study of Triclosan in CD

- 1 Mice. Corning Hazleton Incorporated (CHV), 9200 Leesburg Pike, Vienna, Virginia. Laboratory Study No. CHV 2763

- 100. April 29, 1997. Unpublished.

MRID 44389710: Burns, J.M. (1997) 14

- Day Repeated Dose Dermal Study of Triclosan in Rats. Corning Hazleton Incorporated (CHV), 9200 Leesburg Pike, Vienna, Virginia. Laboratory Study No. CHV 6718

- 102. Unpublished.

MRID 44874001, 44751101: Chambers, P.R. (1999) “Poten tial Tumorigenic and Chronic Toxicity Effects in Prolonged Dietary Administration to Hamsters.” Huntingdon Life Sciences Ltd., Huntingdon, England. CBG 756/972896.

MRID 45307501, 45307502: Van Dijk, Dr. A. (1994) “ 14 

### C

- Triclosan: Absorption, Distributio n, Metabolism, and Elimination after Single/Repeated Oral and Intravenous Administration to Hamsters.” RCC Umweltchemie AG. RCC Project No. 351707.

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Page 58 of 130 MRID 45307503: Van Dijk, Dr. A. (1995) “ 14 

### C

- Triclosan: Absorption, Distribution, Metabolism, and Elim ination after Single/Repeated Oral and Intravenous Administration to Mice.” RCC Umweltchemie AG. RCC Project No. 337781.

Tox Record No. 001955, 001956 (1968)

Tox Record No. 001968 (1977)

Broker, P.C., Gray, V.M., Howell, A. (1988) “Analysis of Metaphase Chromosomes Obtained from CHO Cells Cultured in vitro and Treated with Triclosan.” Huntingdon Research Center, Ltd. ULR 214/88731; Unilever Test #: KC880171. Unpublished.

Capen, C. Toxic Responses of the Endocrine System. In: Casarett and Doull’ s Toxicology: The Basic Science of Poisons, 5 th 

### ed., Curtis D. Klaassen, Ph.D., editor. McGraw

- Hill.

Chen, J. et al. (2007): Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products. Toxicol. Appl. Pha rnacol. 221: 278

- 284.

Crofton, KM; Paul, KB; DeVito, PB; Hedgea, JH. 2007. Short

- term in vivo exposure to the water contaminant triclosan: Evidence for disruption of thyroxine. Environmental Toxicology and Pharmacology 24: 194

– 197.

Eldrige, S. (1995) Cell Proliferation in Rodent Liver. Study conducted by Pathology Associates, Inc. Submitted to EPA (no MRID). Unpublished.

Gee, R.H., Taylor, C.N., Darbre, P.D. (2008): Oestrogenic and androgenic activity of triclosan in breast cancer cells. J. Appl. Toxicol. 28: 78

- 91.

San Sebastia n, J.R., Morgan, J.M. (1993) “Rat Hepatocyte Primary Culture/DNA Repair Test on 39317” Pharmakon Research International, Inc. Pharmakon Study #: PH311

- CP

- 001

- 93. Unpublished.

See, Norman A. (1996) Revi ew and Evaluation of Pharmacology and Toxicology Data Division of Dermatologic and Dental Drug Products (HFD

- 540) Food and Drug Administration. Stoker, T.E., Gibson, E.K., Zorrilla, L.M. (2010) Triclosan exposure modulates estrogen

dependent responses in the female Wistar rat. Toxicol. Sci. 177(1):45

- 53.

Tamura,H., Y. Ishimoto., T. Fujikawa et al. (2006). Use of Structural basis for androgen receptor agonists and Antagonists: Interaction of SPEED 98

- listed chemicals and Related compounds

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Page 59 of 130 with the andro gen receptor based on an In vitro reporter gene assay and 3D

- QSAR. MRID to be Assigned. Bioorganic & Medicinal Chemistry. 14:7160

- 7174.

U.S. EPA 2008). T. E. Stoker and W. Setzer. The Endocrine Disrupting Effects of Triclosan, a common pharmaceutical and personal care product: Alteration of the Thyroid Axis Following a Peri

- juvenile Exposure in the Male Wistar Rat. EPA/600/X

- 08/010.

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Page 60 of 130 

# APPENDIX B: Environmental Fate

For the regist ration review of triclosan, the a gency will review environmental fate and exposure from submitted guideline studies, open literature, and government databases. This final work plan is based on the 2008 RED ( http://www.epa.gov/oppsrrd1/REDs/2340red.pdf ) and additional data from guideline and literature studies that have become available since the 2008
RED.

Under aqueous conditions because triclosan has a pKa of 8.14 (MRID 42027904) , it is expected to exist in a chemically

- neutral (non

- electrically

- charged) form at pH < 7.5 . The neutral or non

ionized state is generally the more bioavailable and toxic form. As the pH of soil or water becomes higher or more basic, triclosan is more likely to be neg atively

- charged and therefore also more mobile in soil as soil too becomes more negatively charged under higher pH. Based on the log Kow value of 4.8, bioconcentration in aquatic organisms is indicated. Oyster and fish bioconcentration data were required by the post

- RED DCI for triclosan with monitoring of its major toxic metabolites such as methyl triclosan.

Open literature studies would indicate that wastewater treatment is likely to remove more than 80% of triclosan and that under anaerobic conditions concentrations in sludge can be expected to increase because the sludge is degrading faster than triclosan. The primary degradation products in chlorinated water treatment include 4

- chloro triclosan, 6

- chloro triclosan, and 4,6

- dichloro triclosan. These open literature studies will be formally reviewed by the a gency during registration review

. A detailed discussion of environmental fate properties of triclosan and its major transformation products methyl triclosan (methoxy triclosan), 2,4

- dichlorophenol, chlorinated triclosan (4

- chloro

- , 6

- chloro

- , and 4,6

- dichloro

- ), and the predominant dioxins such as 2,7/2,8

- dichlorodioxin based on these sources is provided in this appendix. For exposure modeling, a total toxics residue approach will b e used in the risk assessment. This means that estimates of exposure will include consideration of both parent and its major toxic degradates.

Methyl triclosan (methyoxy triclosan) is formed by microorganisms in the presence of oxygen. It has been observ ed to form at significant ( > 10 %) of applied triclosan in aerobic soil (non

flooded top layer of soil) and in WWTPs to a lesser extent.

Chlorophenol compounds (2,4

- dichloro, 4,6

- dichloro

- , 2,6

- dichloro

- , and 2,4,6

- trichloro) are formed as a result of pho todegradation in water (43022608, acceptable study) and the combination of photodegration in water and aquatic metabolism (Buth, 2009). In the Buth (2009 article), dioxins were formed at approximately 1,000X less than the parent triclosan concentration. The Buth (2009) article will be formally reviewed in Registration Review.

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Page 61 of 130 Chlorinated triclosan (4

- chloro

- , 6

- chloro

- , and 4,6

- dichloro

- ) were formed in the Buth (2009) study as a result of chlorination of wastewater. The Buth (2009) article will be for mally reviewed in Registration Review.

Dioxins are formed from triclosan that is exposed to sunlight in water. The predominant dioxins formed include 2,7

- and 2,8

- dichlorodioxin, but others with 3 or 4 chlorine atoms have been observed and include: 1,2,8

- and 2,3,7

- trichlorodioxins and 1,2,3,8

- tetrachlorodioxin (TCDD) in natural waters (Buth, 2009 and Buth, 2010). The Buth (2009 and 2010) articles will be formally reviewed in Registration Review. From a preliminary examination of which dioxins are form ed in these studies, they are not among the congeners of concern for humans or ecological receptors ( i.e ., have no 2,3,7,8

- tetrachlorodibenzo

- p

- dioxin (2,3,7,8

- TCDD) toxicity equivalency factors 17

, 18 

### ) . Appendix F contains a list of the 17 congeners of ecolo gical concern.

To refine estimates of exposure concentrations in surface waters from textile and plastic material preservative use sites, monitoring of textile and plastic material preservative use site effluent wastewater was also required as part of the post

- RED DCI (as noted in Table 7, the special study for Surface Water Monitoring) . Investigation of the plastic manufacturing process where triclosan is used revealed that they are limited to those where the plastic does not come into contact with indust rial process water. Such a lack of contact means there is no environmental exposure pathway for aquatic and terrestrial wildlife. Because there are those plastic manufacturing processes where the plastic does come into contact with industrial process wat er, the label has been changed to limit the use of triclosan as a material preservative to plastic manufacturing that does not come into contact with process water. Monitoring at two textile facilities was recently completed and submitted to the a gency fo r review (MRID 48858101). The results of this study showed that average and maximum in

- stream wastewater concentrations (IWC) for triclosan were 3.2 ng/L and 6.1 ng/L for Facility 1, and 33.1 ng/L and 43.2 ng/L for Facility 2, respectively

. . Methyltriclo san was below detection ( < 1.9 ng/L) at both facilities . The study was found to be acceptable.

To eliminate unnecessary decimals in values, most concentration units in this document are expressed either as nanograms per liter (ng/ L ) for liquids, nanograms per gram (ng/g) for solids (mostly sludge), or picograms per gram ( pg/g ) for solids ( e.g., dioxins in sediments). These units translate to parts

- per

- trillion (ppt) for liquid [1 x 10 - 10 

### %], parts

- per

- tr illion (ppb) for sewage sludge [1 x 10 - 7 

### %], or part s

- per

- trillion for dioxin in sediments.

The physical

- chemical properties of triclosan reveal that triclosan has relatively low water solubility (12 ppm or mg/l), a relatively low vapor pressure (5.2 x 10 - 6 

### mm Hg at 25 o 

### C) (MRID 42027904) , but has limited tendency to volatilize from water with a Henry’s Law values of 5 x 10 - 9 

### atm

- m 3 

### /mol. As a result, it is not expected to volatilize (move from soil or water to air)

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Page 62 of 130 significantly (criteria for non

- volatility is vapor pressure <10 - 6 

### mm Hg). It is expected to exist in a chemically

- neutral (non

- electrically

- charged) form in acidic and neutral pH conditions and a charged state under more basic or alkaline conditions because the pKa is 8.14 (MRID 42027904) . At pH values equivalent to the pKa half of the tricl osan is neutral and half is in a charged state, as the pH drops below the pKa value the neutral state is predominant and as the pH increases above the pKa the charged state is predominant (Price et al., 2010) . For aquatic animals the charged state is usua lly less toxic than the neutral state of a compound. A s the pH of the soil increases, both the soil/sediment and triclosan become more negatively

- charged and the like charges will lead to more association with water in the presence of soil and sediment.

The a gency has received and summarized numerous peer

- reviewed literature studies on the environmental fate of triclosan following the publication of the RED. Given the wide range of values and varying information, the a gency anticipates reviewing critical environmental fate data before publication of the FWP

.


## Abiotic D egradation of Triclosan and Transformation Products

The a gency has received studies on hydrolysis (835.2120) and photodegradation in water (835.2240) that satisfy these data requirements. The studies demonstrate that triclosan is stable to abiotic hydrolysis but degrades rapidly in the presence of light. The hydrolysis study (MRID 42027908) was a preliminary study but it was sufficient to demonstrat e the stability of triclosan at 50 o 

### C. In the photodegradation in water study (MRID 43022608), triclosan degraded with a half

- life of 41 minutes and formed the degradate 2,4

- dichlorophenol (2,4

- DCP) which reached 97 % of the applied parent compound and was stable. Photodegradation in water is ex pected to be the primary route of dissipation for triclosan in shallow, well

- mixed water with no suspended or bottom sediment. However, this route of dissipation in water will be limited in nature by water depth and light attenuation, suspended sediment, shading, and sorption to bottom sediment.

Six aqueous photoloysis studies were found in the literature, and are also cited in Table 1 5

. These studies will be reviewed as part of the registration review action because they appear to provide additional inf ormation on longer half

- lives in the environment as well as the presence of additional degradation products such as dioxins and dichlorohydroxydiphenyl ether (DCHD). From a preliminary examination of which dioxins are formed in these studies, they are not those identified as either of concern for human health or ecological receptors ( i.e ., have no 2,3,7,8

- tetrachlorodibenzo

- p

- dioxin (2,3,7,8

- TCDD) toxicity equivalency factors 19

, 20 

### ) . Table 1 5 also includes a predicted half

- life for photodegradation in air (8 35.2370) which is not anticipated to be critical for the risk assessment because triclosan will not be present in air based on its vapor pressure (5.2 x 10 - 6 

### mm Hg) and Henry’s Law constant (5 x 10 - 9 

### atm m 3 

### mol - 1 

### ).

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Page 63 of 130 Table 15

- Abio tic Degradation of Triclosan and Degradate Formation

Parameter Half

- lives (parent triclosan unless specified) Source (Open literature study unless specified) / Study Classification/ Comments Hydrolysis (OPPTS 835.2120, 161

- 1) pH 4 pH 7 pH 9 Stable at 50°C Pointurier, 1990 ; Guideline study

, MRID 42027908 / Supplemental (preliminary study only), but no additional data expected to be required /

Langer et al., 1972 ; MRID 00046300 / N ot reviewed because it only addressed theories of dioxin formation Aqueous photolysis (OPPTS 835.2240, 161

- 2) Guideline study 41 min Spare, 1993 ; Guideline study

, MRID 43022608 / Acceptable /

Degradate: 2,4

- dichlorophenol (DCP) increased to 94

- 97 % by end of study and did not degrade.

Photolysis in water and degradate formation (OPPTS 835.2210, literature studies) 5 hours in Deionized water and Suwanee River water in U.S. Latch et al ., 2004 ; No MRID assigned /

Quality unknown, study not formally reviewed /

Degradate: 2,4

- DCP formed at up to 3.1 % of applied triclosan

Degradate: 2,8

- dichlorobenzo

- p

- dioxin (2,8

- DCDD) formed at 4

- 12 % of applied triclosan (higher amounts at higher pHs) 4

- 6 min (sunlight) 5

- 8 min (artificial UV light) in i rradiated wastewater samples from Spain Sanchez

- Prado et al ., 2006 ; No MRID assigned / Quality unknown, study not formally reviewed /

Primary degradation products were 2,8

- DCDD and dichlorohydroxydiphenyl ether (DCHD). 2,8

- DCDD reached 100 % of applied triclosan by 5

- 10 minutes with half

- life of ~20 minutes. DCHD reached 100 % by 2 minutes with a half

- life of ~25 minutes. 8 days (freshwater) 4 days (saltwater) 26 days (2,8

- DCDD in freshwater) 11 days (2,8

- DCDD in salt water) Aranami and Readman, 2007 ; No MRID assigned / Quality unknown, study not formally reviewed /

Primary degradation product was 2,8

- DCDD in fresh

and salt water. 2,8

- DCDD peaked at 20 days for both fresh

- and salt

water (study length of 120 days). 2,8

- DCDD reached 60 and 90 % of triclosan in fresh

and salt

- water 23 hours (deionized water) 18 hours (wastewater) Mezcua et al ., 2004 ; No MRID assigned / Quality unknown, study not formally reviewed /

Photodegradation of triclosan in water and wastewater in Spain

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Page 64 of 130 Parameter Half

- lives (parent triclosan unless specified) Source (Open literature study unless specified) / Study Classification/ Comments Photolysis in water and degradate formation (OPPTS 835.2210, literature studies) No specific half

- lives of parent triclosan or degradates in the study Buth et al ., 2009 ; MRID 49159301 / Quality unknown, study not formally reviewed /

Formation of 1,2,8

- and 2,3,7

- trichlorodioxins and 1,2,3,8

- tetrachlorodioxins at up to 2.5 % of 4

- chlo ro triclosan, 6

- chloro triclosan, and 4,6

- dichlorotriclosan in irradiated buffer solutions and natural waters. Indirect photodegradation of dissolved organic matter slower than direct photodegradation of chlorinated triclosans. Photoproducts of triclosan and dioxin conogers in sediment cores of Mississippi River and Lake Pepin in Minnesota where water treatment plant outlet was located (No guideline numbers) Mississippi River Triclosan increased to 10 ng/g in 1998 and decreased to four (4) ng/g in 2008 (last analysis) 2,8

- DCDD, 1,2,8

- TriCDD, 2,3,7

-- Tri

- CDD, and 1,2,3,8

- TCDD increased to 80, 3, 3, and 4 pg/g by 2003, respectively.
Concentrations declined to 20, 1, 1, and 1 pg/g by 2008 (last analysis), respectively

Lake Pepin Triclosan increased to 13

- 14 ng/g in 1998

- 2003 (last analysis) 2,8

- DCDD, 1,2,8

- TriCDD, 2,3,7

-- Tri

- CDD, and 1,2,3,8

- TCDD increased to 85, 3, 3, and 4 pg/g by 2003

- 2008, 1990, 1990

- 2008, and 2008, respectively. 2,8

- DCDD concentrations declined to 70 pg/g by 2008 (last sample), respectively. Buth et al ., 2010 ; MRID 49159302 / Quality unknown, study not formally reviewed /

Cores taken in 2008 Dioxin congeners present in sediment at about 1,000 times lower than triclosan (pg/g versus ng/g (parts

per

- trillion versus parts

- per billion ))

Dioxins in sediment reached 31 % by mass in later depositions 2,8

- DCDD was primary dioxin present in samples (>90 %).

Photolysis in Air (OPPTS 835.2370, 161

- 4) 8 hours (seasonal mean) EPI

- Web 4.1 Program (AOP Program (v1.92) Results for reaction with hydroxyl radicals



### Laboratory Metabolism Properties of Triclosan

The a gency requires laboratory metabolism studies to provide a measure of the biotic degradation potential of a compound in the environment, without the bias from dissipation by leaching or runoff

. The a gency has received acceptable guideline studies on laboratory aerobic soil metabolism (835.4100) and aerobic aquatic metabolism (835.4300). The anaerobic soil

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Page 65 of 130 metabolism (835.4200) data requirement is satisfied with two supplemental open literature studies and the anaerobic aquatic metabolism (835.4400) data requirement has been waived. T he a gency has also received supplemental guideline studies for soil nitrification (OECD 216) and soil respiration (OECD 217) for triclosan that satisf y these data requirements

. Table 16 contains the results and additional details for all laboratory metabolism studies for triclosan.

Aerobic soil metabolism studies represent degradation in the top layer of soil under oxygenated conditions. In the acceptable guideline aerobic soil metabolism study (MRID 47261401)

, t riclosan was found to degrade rapidly and form the transformation product methyl triclosan (methoxy tr iclosan) at up to 17.5 % of applied parent triclosan. The half

- lives of parent triclosan and methyl triclosan were 2.5

- 11 and 39

- 153 days, respectively. Three open literature studies also provided supplemental and useable information on the persistence of parent triclosan but did not measure degradates. E stimates of persistence for parent triclosan were 5.9

- 8.9 days by Carr et al. ( 2011), 12.7

- 15.7 days by Xu et al. ( 2009), and 18 days by Ying et al. ( 2007).

Ying et al. (2007) and Carr et al. (2011) open literature studies provide supplemental and useable information on the persistence of parent triclosan in the flooded , anaerobic, top layer of soil. The results of these studies appear to be contradictory because degrad ation was present in the Carr et al. (2011) study but not the Ying et al. (2011) study. However, differences in soil acclimatization between the two studies are believed by the a gency to be the reason for these differences. The Carr et al. (2011) study us ed acclimatized soils to maximize degradation and the anaerobic half

lives of parent triclosan were found to be 15.3

- 28.8 days. However in the Ying et al. (2007) study where the soils were not acclimatized , parent triclosan was observed to be stable to

an aerobic degradation . Therefore, the a gency considers the Ying et al. (2007) study to be more representative of the environment in general than the Carr et al. (2011) study because the lack of acclimated microorganisms in most anaerobic soils will create p ersistence or stability of triclosan.
The anaerobic aquatic metabolism (835.4400) data requirement for triclosan has been waived as a result of the findings from the submitted open literature anaerobic soil metabolism studies (Carr et al., 2011 and Ying e t al., 2007). Anaerobic aquatic metabolism studies represent the environmental fate of a compound under low oxygen conditions in sediment in the presence of water. It is reasonable to assume that a compound that is stable under anaerobic conditions in

so il will also be stable in sediment.

The acceptable guideline aerobic aquatic metabolism study (MRID 47261402) represent s aerobic (oxygenated) surface water that is associated with sediment. Under aerobic conditions in a water and sediment system (total system ), triclosan partitions from the water phase to the sediment phase by sorption

. The water and total system half

- lives were 1.2

- 1.4 days and 41

- 58 days, respectively. No major or significant degradates ( > 10 % of applied triclosan) were detec ted. The minor degradate methyl triclosan was formed at 3.4

- 4.8 % of applied triclosan

. T he a gency has received guideline studies for soil nitrification (OECD 216) and soil respiration (OECD 217) for triclosan. While th ese studies are considered to co ntain supplemental information, no additional data are expected to be required. At up to 2 ppm (mg/kg) in soil, parent triclosan did not inhibit soil nitrification (MRID 47261403) or soil respiration (MRID 47261404)

.

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Page 66 of 130 Table 16

- Metabolism of Triclosan with Formation of Degradates

Parameter Half

- life of Triclosan (unless specified) Source (Open literature unless specified) / Study Classification/ Comments Aerobic Soil Metabolism (OPPTS 835.4100, 162

- 1)

Gartenecker loam, 1.73 % OC, Swiss soil , 20 o C

Speyer 5M, sandy loam, 1.39 % OC, German soil, 10 o C

Speyer 5M, sandy loam, 1.39 % OC, German soil, 20 o C

Senozoan clay loam, 1.04 % OC, French soil , 20 o C Half

- lives

2.7 days (parent) 39 days (methyl triclosan)

11 days (p arent) Stable (methyl triclosan)

2.5 days (parent) 97 days (methyl triclosan)

3.3 days ( parent ) 153 days (methyl triclosan) Adam, 2007 ; Guideline study MRID 47261401 / Acceptable Unknown triclosan source, purity 99.3 % Methyl triclosan purity 99.6 %

Methyl Triclosan (Max of 13.4 % by 14 days, declining to 4.2 % by 124 days (end of study)

Max of 14.5 % by 61 days, declining to 13.3 % by 124 days

Max of 17.5 % by 28 days, declining to 12.5 % by 124 days

Max of 24 % by 28 days, declining to 17.3 % by 124 days Loam soil, Study conducted at 22 o C 18 days in non

- sterile loam soil Stable in sterile loam soil Ying et al., 2007 ; MRID 49197201 / SUPPLEMENTAL / /

Triclosan from Fluka Chemicals, unknown purity No degradate analysis

Loam soils, Temperature not specified 5.9 and 8.9 days in WWTP

exposed and non

- WWTP exposed loam soils Stable in sterile loam soil Carr et al., 2011 ; MRID 49197202 / S UPPLEMENTAL/ Triclosan from Sigma Aldrich Labs, >98 % pure No degradate analysis

Loamy sand, sandy loam, silty clay, and silt loam Study conducted at 20 + 2 o C 13.6, 14.2, 12.7, and 15.7 days Loamy sand, sandy loam, silty clay, and silt loam

35.4 days in sterile loamy sand 20 days in non

- sterile loamy sand Xu et al., 2009 ; MRID 49159303 / S UPPLEMENTAL/

No degradate analysis

Anaerobic Soil Metabolism (835.4200, 162

- 2)

Loam soil, Study conducted at 22 o C Stable in non

- sterile and sterile anaerobic loam soil Ying et al., 2007 ; MRID 49197201 / SUPPLEMENTAL/ Triclosan from Fluka Chemicals, unknown purity No degradate analysis

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Page 67 of 130 Parameter Half

- life of Triclosan (unless specified) Source (Open literature unless specified) / Study Classification/ Comments Loam soil, Temperature not specified 28.8 and 15.3 days in WWTP

exposed and non

- WWTP exposed loam soils Stable in sterile anaerobic loam soil Carr et al., 2011 ; MRID 49197202 / SUPPLEMENTAL/ Triclosan from Sigma Aldrich Labs, >98 % pure No degradate analysis Anaerobic Aquatic Metabolism (OPPTS 835. 4 4 00 ) Waived Waived because Carr (2011) and Ying (2007) studies in soil support conclusion of stability in anaerobic aquatic sediment. Aerobic Aquatic Metabolism (OPPTS 835.4400)

Pond Water

Pond Sediment

Pond System

River Water

River Sediment

River System 1.4 days (parent) No significant degradates

56 days (parent) Formation decline analysis based on sorption to sediment

58 days (parent) Whole system

1.2 days (parent) No significant degradates

56 (parent) No significant degradates Formation decline analysis based on sorption to sediment

41 days (parent) Whole system Adam, 2006 ; Guideline study MRID 4726140 2

, / Acceptable Study conducted at 20 + 2 o C Unknown triclosan source, purity 99.3 % Methyl triclosan purity 99.6 % Methyl triclosan formed at 3.4

- 4.8 % of applied triclosan No significant degradates formed ( > 10 % of applied parent triclosan)

Soil respiration (OECD 217) No effect of triclosan treatments up to 2 ppm Volkel, 2006 , Guideline study/ MRID 47261403 Supplemental but no additional data expected to be required Soil nitrification (OECD 216) No effect of triclosan
treatments up to 2 ppm Volkel, 2007 ; Guideline study

, MRID 47261404 / Supplemental but no additional data expected to be required /



### Ionization of Triclosan and Environmental pHs

Like most compounds with an acid ionizable functional group, triclosan will exist in both an un

ionized (protonated) and ionized (non

- protonated) forms depending on the environmental pH range. The pH at which triclosan exists in even amounts (50 %) of bot h un

- ionized and ionized forms is the pKa, which for triclosan is 8.14 at 20 o 

### C. While temperature variations can affect the amount of ionization by pH, 20 o 

### C is a representative environmental temperature and is relevant

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Page 68 of 130 for environmental risk assessment. At pH values that are one, two, and three units below the pKa, 90, 99, and 99.9 % of triclosan is expected to be in the un

- ionized (protonated form). At pH values that are above the pKa, 90, 99, and 99.9 % of triclosan is expected to be in the ionized (non

- protonated) state. The absence or presence or ionization is calculated by the Henderson

Hasselback Equation ( http://chemistry.about.com/od/acidsbase1/a/hendersonhasselbalch.htm ). Typical soil pH values range from pH 5 to 7 in more humid areas, while soils in more arid areas can range up to pH 9. Therefore, 90

- 99 % of triclosan in soil is expected to be present in the

non

- ionized form in more humid areas and up to 90 % may be present in the ionized form in arid areas. Table 17 below provides information on the extent of non

- ionization/ionization of triclosan by pH.

Table 17

- Effect of pH on the Ionization of Triclosan at 20 o 

### C

pH Non

- Ionized Triclosan (%) Ionized Triclosan (%)

5.14 99.9 0.1 6.14 99 1 7.14 90 10 8.14 (pKa) 50 50 9.14 10 90

Leaching

- Adsorption

- Desorption (835.1230)

The a gency is aware of three open literature leaching

- adsorption

- desorption studies for triclosan (Xu et al., 2009; Cha and Cupples, 2010; Duran

- Alvarez et al., 2012)

. The Xu et al (2009 ) study was reviewed and classified as supplemental information. The results indicate that paren t triclosan is strongly sorbed to soil. T he remaining stud ies by Cha and Cupples ( 2010 ) and Duran

- Alvarez et al

., (2012) have not been reviewed but the a gency anticipates reviewing these studies prior to the risk assessment

.

Table 1 8 below contains the leaching and adsorption

- desorption data for triclosan. The extent of sorption to soil in the presence of water will depend on the environmental pH and the degree of

non

- ionization/ionization of triclosan (Thompson and Goyne, 2012) . Th e hydroxyl functional group of triclosan will carry a neutral charge in more humid areas with lower pH values and a negative charge in arid areas with high pH values. Because soil has a negative charge, sorption will decrease as the pH of the soil increas es.

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Page 69 of 130 Table 18

- Leaching and Adsorption

- Desorption of Triclosan to Soil and Sediment

Parameter Value Source (Open literature study unless specified) / Study Classification/ Comments Leaching

- Adsorption

- Desorption (OPPTS 835.1230, 163

- 1) Kd values of 9.7, 133, 273, and 52 ml/g Koc values of 2,188, 23,988, 8,709, and 3,631 ml/g in loamy sand, sandy loam, silty clay, and silt loam soils Xu et al., 2009 ; MRID 49159303
SUPPLEMENTAL/ Study conducted at 20 + 2 o C

Kd values of 33, 55, and 51 ml/g in loamy sand, sandy loam, and sand soils Koc values of 5,613, 6,310, and 3,968 ml/g Cha and Cupples, 2010 ; No MRID assigned / Quality unknown, study not formally reviewed /

Sorption coefficients (Kd) for triclosan in the smectite

- based (shrink

- swell) silty clay topsoil and clay subsoil

Kd values for triclosan were 64.9 ml/g and 19.2 ml/g, respectively. Triclosan

so r ption was irreversible.

The organic carbon content of the soils and sludge were 2.5, 1.8, and 181 mg/g with a pH
range of 8.0

- 8.1 for soil and 7.6 for sludge. The pre

existing triclosan concentrations were 9.7, 6.3, and 1,401 ng/g or ng/l, respectively. Duran

- Alvarez et al., 2012 ; No MRID assigned / Quality unknown, study not formally reviewed.



### Terrestrial Field Dissipation, Leaching, Runoff, and Crop Uptake (835.6100)

Triclosan has been commonly detected in sewage sludge both in the United States and in other countries . As a result triclosan may potentially be applied to agricultural fields as a contaminant of s ewage sludge land applications. Triclosan input from EPA registered pesticidal use patterns is expected to be primarily from industrial uses in textile manufacturing and would therefore have limited geographic impact. The geographically

- widespread nature of the detections in the environment indicate s that that while the EPA registered antimicrobial uses may potentially contribute to the exposure in some localized areas with industrial sources, the primary

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Page 70 of 130 contribution is expected to be from the personal care product uses . The a gency is aware of 1 4 field dissipation studies from the open literature; these are listed in Table 1 9 . None of these studies have been reviewed by the a gency, but they will be reviewed during the risk assessment ph ase to determine their usefulness in the risk assessment. Some of the studies appear more than once in the table because they contain information on overall environmental fate and not just dissipation.

Table 19

- Terrestrial Fie ld Dissipation, Surface Runoff, Leaching, and Crop Uptake

Parameter 

### Value Source (Open literature study unless specified) / Study Classification/ Comments

Degradation in sewage

sludge amended soils (no guideline number) Half

- lives of 0.4

- 12.5 and 0.6

- 7 days in sandy loam soil Degradation faster in liquid municipal biosolids than in de

watered municipal biosolids Al

- Rajab et al., 2009/ No MRID assigned Quality unknown, study not formally reviewed.
Canada No characterization of significant non

extractable residues

Half

- lives of 13.6, 14.2, 12. 7, and 15. 7 days in loamy sand, sandy loam silt loam, and silty clay soils Xu et al., 2009 / No MRID assigned Quality unknown, study not formally reviewed. No degradate analysis

Half

- lives of 29

- 83 days for loamy sand, sandy loam, and sandy soils After 100 days, 21

- 25, 16

- 43, and 20

- 45 % of triclosan remained Cha and Cupples, 2010 / No MRID assigned Quality unknown, study not formally reviewed. No degradate analysis
Half

- life and 90 % dissipation of 23 and 77 days LOQ was reached by 111 days Topp et al., 2008/ No MRID assigned Quality unknown, study not formally reviewed. Ontario, Canada
Silt loam soil with wheat stubble No degradate analysis Triclosan at up to 100 mg/kg (ppm) did not affect the degradation of estrogen molecules
The half

- lives for 10 and 100 mg/kg triclosan were about 14

- days but 1,000 ppm rate did not reach half

- life Total degradation of estrogens by 14 days at 10

- 100 mg/kg triclosan Limited degradation of estrogens at 1,000 mg/kg triclosan Shareef et al., 2009/ No MRID assigned Quality unknown, study not formally reviewed.
Australia Sandy soil

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Page 71 of 130 Parameter 

### Value Source (Open literature study unless specified) / Study Classification/ Comments

Topp et al., 2008 / No MRID assigned Quality unknown, study not formally reviewed. Australia Sandy soil

Surface runoff from treated soil Runoff concentrations of 26 and 258 ng/l from injected and surface

applied liquid sludge / No MRID assigned Quality unknown, study not formally reviewed.

Tile drainage concentrations Triclosan present in water for 9 months

. Maximum concentration of 230 ng/l in tile water. Sewage concentrations of 240

- 3,680 ng/l in 2005 and 2006 Bester and Schafer, 2009
/ No MRID assigned Quality unknown, study not formally reviewed.K d of 160 ml/g

Triclosan Maximum concentration of 14,000 ng/g in treated soil
reached 74 ng/l in tile water. There was no measurable crop uptake in wheat. Edwards et al., 2012 / Edwards et al., 2009b No MRID assigned Quality unknown, study not formally reviewed.

Field dissipation, leaching, and crop uptake Triclosan reached 74 ng/l in tile drainage at 3,676 ng/l from surface application
There was no measurable crop uptake in tiles Lapen et al., 2012 No MRID assigned Ontario, Canada Quality unknown, study not formally reviewed.

Leaching in sludge

- treated fields (no guideline) Triclosan detected in tile drainage at 150 ng/l Up to 2.2 % of applied triclosan in leachate (max in sandy loam soil) Lapen et al., 2010 / 2.1 % OC, Clay loam No MRID assigned Quality unknown, study not formally reviewed.

No degradate analysis
Soil columns from MexicoTriclosan concentrations in UK. Up to 2.2 % of applied triclosan in leachate (max in sandy loam soil) Gibson et al., 2012 / No MRID assigned Quality unknown, study not formally reviewed.Soils in Mexico treated with sludge repeatedly for 10

- 90 years and cropped

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Page 72 of 130 Parameter 

### Value Source (Open literature study unless specified) / Study Classification/ Comments

Sorption coefficients (Kd) for triclosan present in top 10 cm as either parent compound or methyl triclosan were 64.9 ml/g and 27

- 42 % methyl triclosan).

The organic ca rbon content of the soils and sludge were 2.5, 1.8, and 181 mg/g with a pH range of 8.0

- 8.1 for soil and 7.6 for sludge. The pre

existing triclosan concentrations were 9.7, 6.3, and 1,401 ng/g or ng/l, respectively. Butler et al., 2012 / No MRID assigned Q uality unknown, study not formally reviewed.

Sandy clay loam Half

- life of 182

- 193 days Detectable residues (>56 ng/g) up to 858 days in outdoor pots Walters et al

., 2010 / No MRID assigned

Quality unknown, study not formally reviewed
U.S. soils with h igh treatment rate



### Environmental Monitoring Studies for Triclosan

Triclosan has been detected in surface water and sediment. The geographically

- widespread nature of the detections in the environment indicates that that while the EPA uses may contribute

to the exposure in some localized areas with industrial sources, the main contributor is the personal care product uses in most areas without industrial sources 21 

### . Surface water and sediment exposure most likely result from the effluent from WWTPs which contains small amounts of triclosan relative to the portion that is sorbed onto sewage sludge. The studies cited below in Table 20 demonstrate that triclosan is typically found in water in the ng/l (parts

- per

trillion, ppt) concentration range and in sediment in the ng/g (parts

- per

- billion, ppb) concentration range. There were 17 articles for surface water occurrence, five for finished reclaimed wastewater and gr ound water, and one for bottom sediment. The higher detections in surface water and bottom sediment and the lower concentrations in the landfill leachate and wells are consistent with the fact that triclosan has a limited water solubility (12 mg/l) and a ppears to be strongly sorbed to soils and sediments. The Buth (2010) article also contains information on

21 According to the 200

- 2005 Kline Report around 120,000 pounds of triclosan are used annually for antimicrobial pesticidal uses ; this makes up less than 1% of the overall annual production of triclosan in the U

. S

. of around 10 million pounds ( Kline , 20 05 ).

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Page 73 of 130 the relative amounts of the chlorinated triclosan transformation products formed in the environment. None of these studies have been formally review ed, but will be reviewed during Registration Review to determine their usefulness in risk assessment.

Table 20

- Environmental Monitoring Studies for Triclosan

Medium Range Unit Average Median No. Samples No. Detections Percent Detection References (Open literature study unless specified)/ Study Classification/ Comments

Surface Water 0.01

- 2.3 ng/l 0.19 0.05 85 45 53 Barnes et al., 2002 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Various streams in U.S.

, USGS

<3

- 10 ng/l NA NA NA NA NA Bester (2005) ; No MRID assigned/ Quality unknown, study not formally reviewed /

Ruhr River Catchment in Germany

1.6

- 29 ng/l 10.9 12.4 29 21 72 Boyd et al, 2004 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Stormwater canals and Bayou St. John in New Orleans

60

- 80 ng/l 70 70 3 2 66 Coogan et al, 2007 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Denton, TX

0.398

-

1.02 ng/l 0.627 NA 2 2 100 DeLorenzo et al, 2008 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Toxicity of triclosan and formation of methyl triclosan in estuarine systems

, USGS

.

4.9

- 13.7 ng/l 7.5 NA 13.7 13.7 100 Fair et al, 2009 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Estuarine water in Charleston Harbor

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Page 74 of 130 Medium Range Unit Average Median No. Samples No. Detections Percent Detection References (Open literature study unless specified)/ Study Classification/ Comments

0.021

- 1 (RL=1) ng/l 0.89 (includes

ND) 1 5 47 10.6 Focazio et al., 2008 ; No MRID assigned/ Quality unknown, study not formally reviewed /

49 locations
18 states and Puerto Rico Unfiltered samples USGS

110

- 640 ng/l NA 200 and 110 for 1 st and second down

stream locations 10 for each location 6 7 60

- 70 Glassmeyer et al., 2005 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Downstream of 10 WWTPs

, USGS

2,300 (maxi

mum) ng/l 176 50 145 90 62 Kolpin et al, 2002 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Streams with minimal dilution Unfiltered water samples

, USGS

10

- 4,010 ng/l 193 186 36 36 100 Lishman et al., 2006 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Thames River, Canada 12 WWTP plants in Canada with 1,215

- 105,000 m3/day treated input. Lagoon, activated sludge, and activated sludge/ filtration treatments
35

- 100 % residential

70

- 650 ng/l NA NA NA NA NA Poiger et al., 2003 and Linstrom et al., 2002 ; No MRID assigned/ Quality unknown, study not formally /

34

- 92 % removal p. 172 of Australia Report

12 ng/l 12 12 3 1 33 Vanderford and Snyder, 2006 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Stream with >90 % treated wastewater 4 o treatment

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Page 75 of 130 Medium Range Unit Average Median No. Samples No. Detections Percent Detection References (Open literature study unless specified)/ Study Classification/ Comments

0.4

- 85

(dry weight) ng/g N/A N/A 24 24 (>0.4 ng/l) 100 Venkatesan et al., 2010 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Sediment in Minnesota freshwater bodies 58 % of samples downstream of WWTPs were greater than upstream

1

- 9

26 ng/l

ng/g 3 water

26 sedi

ment NA 41 water

12 sedi

ment 12 NA Wilson et al, 2009 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Lower Hudson River Estuary

1,130 (maxi

mum) ng/l NA NA 14 9 64 Young et al, 2008 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Baltimore City and County watersheds 9

- 60 % removal

193 ng/l NA NA 4 1 25 Yu and Chu, 2009 ; No MRID assigned/ Quality unknown, study not formally reviewed

West Prong Litt l e River, East Tennessee

Finished Reclaimed

Waste Water and

Ground Water 0.021

- 1 (RL=1) ng/l 0.89 (includes

ND) 1 47 5 10.6 Barnes et al., 2008 ; No MRID assigned/ Quality unknown, study not formally reviewed /

25 samples in 12 states and Puerto Rico 441 wells sampled

, USGS

<1.0 NA NA NA 5 3 60 Buszka et al, 2009 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Leachate from landfills in GW in Indiana , USGS

No detection

s NA NA NA 11 0 0 Katz and Griffin, 2008 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Compounds in Karst water in Florida

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Page 76 of 130 Medium Range Unit Average Median No. Samples No. Detections Percent Detection References (Open literature study unless specified)/ Study Classification/ Comments

280

- 2,110 ng/l 1,430 NA 6 3 50 Loraine and Pettigrove, 2006 ; No MRID assigned/ Quality unknown, study not formally reviewed /

Reclaimed wastewater in California

Bottom Sediment 4

- 10

13

- 14 ng/g 10 (1998) 4 (2008)

13.5 (1998

- 2003) 10 (1998) 4 (2008)

13.5 (1998

- 2003) 2 2 100 Buth et al., 2010 ; MRID 49159302/ Quality unknown, study not formally reviewed /

Concentrations of 4

- chloro triclosan, 6

- chloro triclosan, and 4,6

- dichloro triclosan reached 1

- 80 pg/g in Mississippi River (most<20 pg/g )
50

- 85 pg/g for 2,8

- DCDD Up to 4 pg/g for others in Lake Pepin

.

Triclosan Mississippi River sediment in Minnesota , and Lake Pepin sediment triclosan concentrations , respectively



### Bioconcentration in Fish (835.1730) and other Aquatic Organisms

Triclosan and its transformation product methyl triclosan have been detected in fish, snails, dolphins, and algae in both freshwater and brackish/salt water (Table 21) . Acceptable studies for bioconcentration in fish (850.1230) and in oysters (850.1710) are still needed because none have been submitted to the a gency and in general the information in the open literature appears to be correlative in nature but do not pro vide a bioconcentration values which can be used in a quantitative risk assessment. T he a gency required the bioconcentration in fish and oyster studies as part of the post

- RED DCI

. Triclosan and methyl triclosan are likely to accumulate in aquatic organisms because the log P (log Kow) values are 4.76 and 5.2 (>3, level of concern for bioconcentration and bioaccumulation), respectively, and both compounds will need to be addressed i n eac h study. The field monitoring studies in Table 21 will be reviewed to gain any additional information that may be used for risk characterization.

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Page 77 of 130 Table 21

– Biological Field Monitoring of Aquatic Organisms

Parameter Value Source (Open literature study unless specified) / Study Classification/ Comments BCF (ratio of organism concentration to
water concentration) (OPPTS 850.1730, 165

- 4) Concentration range of 10,687

- 16,492 and 51,041

- 92,504 ng/g for triclosan and methyl triclosan, respectively. Triclosan detected in few fish samples
Concentration in bream has increased since 1990’s Methyl triclosan detected in all. Boehmer et al., 2004 ; No MRID assigned Quality unknown, study not formally reviewed /

Methyl triclosan studied German Rivers

Triclosan detected at 0.24

- 4.4 ug/g in fish upstream of STP
35

- 120 ug/g in caged fish in sewage waste
Triclosan detected at 14

- 80 ug/ml of bile
No evidence of estrogenic activity Houtman et al., 2004 ; No MRID assigned / Quality unkno wn, study not formally reviewed/

Netherlands No degradates analyzed Bottlenose dolphins ( Tursiops truncatus ) 0.12

- 0.27 ng/g (mean of 0.18 ng/g) with 31 % detection frequency at Charleston

. Influent and effluent concentrations of 2,800

- 3,400 and 190 ng/l at Charleston, SC.

Bottlenose dolphins ( Tursiops truncatus ) 0.025

- 0.11 ng/g (mean of 0.072) with 23 % detection in Florida. Charleston estuarine concentrations wer e 4.9

- 14 ng/l (7.5 ng/l average)

. Fair et al., 2009 ; No MRID assigned / Quality unknown, study not formally reviewed /

United States No degradates analyzed

Methyl triclosan was detected in all 29 male common carp ( Cyprinus carpio ) from Las Vegas Bay with a mean concentration of 596 ng/g wet weight. The halogenated analogs were detected less frequently (21%

– 76%) and at much lower concentrations (<51 μg/g ww) Leiker et al., 2008 ; No MRID assigned / Quality unknown, study not formally reviewed /

United States

, USGS Methyl triclosan

BCF value of 1.7X in Mediterranean mussel ( Mytilus galloprovincialis )
30

- day concentration of 461 ng/g dry weight of triclosan in 300 ng/l Depuration half

- life of 12 days

— slower than uptake rates Gatidou et al., 2010 ; No MRID assigned / Quality unknown, study not formally reviewed.

Greece

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Page 78 of 13 0 Parameter Value Source (Open literature study unless specified) / Study Classification/ Comments

Bioconcentration in snails and algae (no guideline) Triclosan concentrations of 112, 59,000, and 162,000 ppt in water, snails, and algae BCF values of 500 and 1,400 in snails and algae

.

Methyl triclosan concentrations of 0.041, 50, and 50 ppb in water, snails, and algae BCF values of 1,200 in snails and algae Methyl triclosan concentrations of 4.2

- 365 ng/g lipid in different fish (most <100 ng/g) Coogan and LaPoint, 2008 ; No MRID assigned / Quality unknown, study not formally reviewed /

United States Methyl triclosan
Dissertation at: http://digital.library.unt.edu/ark:/67531/metadc 3986/m2/1/h igh_res_d/dissertation.pdf



### Wastewater Treatment Studies

Activated Sludge, Respiration Inhibition

The a gency is anticipating requiring a ctivated s ludge r espiration i nhibition (ASRI) data because of the potential for triclosan to be discharged to WWTPs and affect the microbial components of WWTPs receiving effluent from textile and fabric materials preservative uses

. ASRI data allows the agency to evaluate the potential hazard to such systems from triclosan loading.

Activated Sludge, Sorption Isotherm

The a gency is assuming a removal of 80 % for parent triclosan by sorption to activated sludge based on the results of Lee et al. (2003). This literature study measured triclosan concentrations in water in WWTPs before and after sludge sorption, and averag e percent removal was 80 %.

Bio tic D egradation

The a gency has received data for the dissipation of triclosan under WWTP conditions. The acceptable guideline WWTP guideline studies for the environmental fate of triclosan ( Christensen 1994a and 1994b) d emonstrate the degradation of triclosan under aerobic conditions with a half

- life of 5.2 days in aerobic sludge, but also demonstrate the lack of degradation under anaerobic conditions. The unreviewed Behera (2010) literature study on sorption to activate d carbon may be representative of the sorption to activated sludge, and the appropriateness and usefulness of the study will be addressed prior to risk assessment. Table 22 contains the results of WWTP studies for triclosan.

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Page 79 of 130 Table 22 WWTP Studies for Triclosan

Parameter Half

- life of Triclosan (unless specified) Source (Open literature unless specified) / Study Classification/ Comments Simulation Tests to Assess the Primary and Ultimate Biodegradability of Chemicals Discharged to Wastewater (O CPPS 835.3280 ) Stable in anaerobic sludge Christensen, 1994a ; Guideline study

, MRID 47261406 / Acceptable

Simulation Tests to Assess the Primary and Ultimate Biodegradability of Chemicals Discharged to Wastewater (O CPP S 835.3280 ) 5.2 days in aerobic sludge Christensen, 1994b ; Guideline study

, MRID 47261407 / Acceptable /

57.1 % CO 2 evolution by 57 days 10.2 % organic volatiles by 57 days Sorption to Activated Carbon (no test guideline) Freundlich K f values of 1.13

- 3.03 million Behera et al., 2010 ; No MRID assigned / Quality unknown, study not formally reviewed /



### Environmental Exposure from Textile Impregnation Facilities

The a gency as part of the post

- RED DCI required field monitoring studies ( sent on October 5, 2011, # GDCI 054901

- 30197) ) for EPA registered uses in plastic and textile manufacturing facilities. The technical manufacturing label was modified to limit use in plastic manufacturing

to those where the plastic does not come into contact with water during manufacturing. Based on this label change there should be no environmental exposure from use at plastic manufacturing facilities and the field monitoring requirement was dropped. The r egistrants submitted an acceptable textile monitoring study in response to the post

- RED DCI (MRID 48858101)

. Two textile facilities were chosen to collect data on the concentrations of triclosan and methyl triclosan present in their effluent wastewaters a fter triclosan was applied to textiles using the exhaustion process (Table 2 3 ). This process uses a jet machine to apply triclosan and other ingredients to textiles at high temperature. At the two facilities selected the spent or remaining solution from the exhaustion process is discharged to the on

- site wastewater treatment plants before the resulting effluent is discharged to surface waters. Monitoring specifically at facilities that have their own treatment facilities allows better identification of t riclosan attributable to its material preservative use from FDA uses. The discharge to surface waters at these facilities is conducted under National Pollutant Discharge Elimination System (NPDES) permits.

In order to obtain good sample regimes, it was determined that for facility 1, stable operations could possibly be achieved in 2 to 3 weeks following the initiation of the production run. It was

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Page 80 of 130 further noted that stable effluent concentration of the active attained peak concentration in 7 day cyclic fashion consecutively.

For facilit ies 1 and 2, the best sample regime was obtained through a 5 consecutive, 24 hour composite effluent samples.

In all 22 samples were analyzed for presence and quantification of triclosan and methyl triclosan for both facilities. The average and maximum triclosan and methyl triclosan concentrations in effluent and in

- stream under 7Q10 conditions are listed in Tabl e 23

Table 23

- Textile Monitoring Facility Characteristics Application/ Parameter/ Characteristics Facility # 1 Facility # 2 Comments

Use pattern Intermittently used Constantly used

- Number of days each facility was processing textiles in study period 

### 327 pounds 636 pounds

-

WWTP effluent flow
rates (MGD) Min: 0.09, A v g: 0.21, M ax:0.7 Min:1.04, A v g : 1.47, Max: 1.81 - Hydraulic retention time (days) Min: 13, A v g : 43, Ma x: 100 Min:6, A v g: 7, M ax: 1 0

- Aeration lagoon volume (MG) 2.25 2 EQ Basin for Fac#2 Aeration lagoon MLSS 2500 mg/L 3.8 Aeration lagoon 1 & 2 Clarifier volume (MG) 0.147 MG 0.021 MG Mixed/Floc tank
Polishing pond volume (MG) 6.5 0.542 Clarifier 1
Polishing pond depth 4 ft 0.542 MG Clarifier 2 Polishing pond area 5 acres each 0.033382 MG Post Aeration Avg: average; MG: million gallons; MGD: million gallons per day; Min: minimum; Max: maximum

Table 24

- Textile Triclosan and Methyl Triclosan Monitoring Concentrations Analyte Average (μ g/L) Maximum (μ g/L ) Triclosan Facility 1 0.099 0.190 Triclosan Facility 2 Triclosan Facility 1 IWC 0.0032 0.0061 Triclosan Facility 2 IWC 0.033 1 0.043 2 Methyl triclosan: Facility 1 and Facility 2 <0.0018 <0.0018

IWC: in

- stream waste concentration (based on NPDES 7Q10 flow).

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Page 81 of 130 

# APPENDIX C : Ecotoxicity Profile

Terrestrial Organisms

Birds

The requirement for acute oral toxicity data for triclosan is satisfied. An acute oral toxicity study using the technical grade of the active ingredient (TGAI) is used to establish the toxicity of triclosan to birds. The preferred test species is either the mallard ( Anas platyrhynchos ) or the northern bobwhite ( Colinus virginianus ). Three studies have been submitted ( Table 24) . One study each with the mallard and northern bobwhite with TGAI categorize triclosan as being slightly to practically nontoxic to birds (LD 50 

### values = 825 and >2150 mg ai/kg bw/day, respectively). A formulation containing 3.89% ai was found to be practically nontoxic (northern bobwhite LD 50 

### >2000 mg ai/kg bw/day).

The requirement for subacute dietary toxicity data for triclosan i s satisfied. A subacute dietary study using the TGAI is required on a case

- by

- case basis depending on the results of lower

- tier ecological studies and pertinent environmental fate characteristics in order to establish the toxicity of a chemical to avian s pecies. The results of two subacute dietary toxicity studies, submitted for triclosan, are provided in Table 24 , one with triclosan (99.7% ai) and one a formulation of triclosan (3.89%). An LC 50 

### of greater than 5000 ppm ai categorizes triclosan as practi cally nontoxic to birds on an acute dietary basis.

For the triclosan use patterns chronic exposure is not considered likely, so an avian reproductive study is not expected to be required at this time.

Table 25

- Toxicity of Triclosan to Birds

Species Chemical, % Active Ingredient (ai) Endpoint Toxicity Category Study Classification/ Source/ Comments

Mallard duck ( Anas platyrhynchos ), 19 weeks old 

### Triclosan 99.7% LD 50 >2143 mg ai/kg

- bw

NOAEL > 2143 mg ai/kg

- bw Relatively nontoxic Acceptable/ Pedersen and Helsten, 1993a MRID 43022603/

- 14

- day test duration
Bobwhite quail ( Colinus virginianus ), 21 weeks old Triclosan 99.7% LD 50 = 822 mg ai/kg

- bw

NOEL = <147mg ai/kg

- bw (diarrhea, lethargy) Slightly toxic Acceptable/ Pedersen and Helsten, 1993b MRID 43022602/

- 14

- day test duration

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Page 82 of 130 Species Chemical, % Active Ingredient (ai) Endpoint Toxicity Category Study Classification/ Source/ Comments

Bobwhite quail ( Colinus virginianus ), adults Triclosan (Issue Plus II) 3.89% LD 50 > 77.8 mg ai/kg

- bw ( LD 50 > 2000 mg f/kg

- bw)

NOAEL >77.8 mg ai/kg

- bw (NOAEL > 2000 mg f/kg

- bw) No mortality or sublethal effects Formulation is Relatively

nontoxic Acceptable for formulated product/ Terrell, 1989a MRID 41008910/

Bobwhite quail ( Colinus virginianus ), 13 days old Triclosan 99.7% LC 50 (diet) > 4985 ppm ai (LC 50 (diet) > 5000 ppm f) (at highest treatment 40% mortality, 95% CI 12.1

– 73.8% mortality)

NOAEC = 1246 ppm ai (mortality) Relatively nontoxic Supplemental/ Pedersen and Helsten, 1993c MRID 43022604/

- 8

- day test duration (5 days exposed, 3 days post exposure)

Bobwhite quail ( Colinus virginianus ), 7

- 10 days old Triclosan (Issue Plus II) 3.89% LC 50 (diet) > 194 ppm ai (LC 50 (diet) > 5000 ppm f)

NOAEC = N.R. No mortality or sulblethal effects at limit dose Formulation is Relatively

nontoxic Acceptable/ Terrell, 1989b MRID 41008911/

- 8

- day test duration (5 days exposed, 3

post

- exposure)



### Mammals

Wild mammal testing is higher tier effects testing and is not typically required by the a gency. In most cases, rat toxicity values obtained from studies conducted to support data requirements for human health risk assessments substitute for wild mammal testing. Acute oral toxicity and two

generation rat reproduction data are available for tr iclosan. Refer to Appendix A , Toxicology Profile, of this document for a description of laboratory mammalian toxicity data. Information about triclosan’s potential as an endocrine disruptor is also described in Appendix A

.

Based on submitted mammalian da ta triclosan is considered practically nontoxic to mammals on an acute basis (rat LD 50 

### : >5000 mg ai/kg

- bw; MRID 432069

- 01). The reproductive/developmental NOAEL is l000 ppm (50 mg ai/kg

- bw/day; MRID 406237

- 01 ). No additional mammalian data are expected to be required at this time to conduct a risk assessment for mammalian wildlife.

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Page 83 of 130 Nontarget Beneficial Terrestrial Insects

The triclosan use patterns are not expected to result in exposure of nontarget beneficial terrestrial insects. Data are not expected to be required for the triclosan uses. 

## Toxicity to Aquatic Receptors

In the water column triclosan is highly acutely toxic to freshwater fish and invertebrates, and also has a detrimental impact on reproduction in the parts per billion range (T able 25) . One available subchronic sediment toxicity study indicates that triclosan does not adversely impact survival, emergence or development rate of freshwater benthic invertebrates (Table 25) . Acute and chronic data are lacking for estuarine/marine fish and crustaceans but are needed for risk assessment. Prediction models were run to obtain estimates of triclosan toxicity for estuarine/marine fish and a shrimp. Acute data is also lacking for an estuarine/marine mollusk. A study is expected to be re quire d

. Freshwater Fish and Amphibians

- Triclosan

For triclosan, material preservative uses, an acute toxicity study with a coldwater and a warm water species

, and a chronic test using the TGAI is used to establish the toxicity of triclosan to freshwater fish . The preferred acute test species are rainbow trout ( Oncorhynchus mykiss ) and bluegill sunfish ( Lepomis macrochirus ). B ecause there is potential for endocrine effects

, a fish full life cycle rather than an early life stage is used to establish chronic reproductive effects from triclosan . Acute toxicity for the species tested in the fish full life cycle test is used in the calculation of an acceptable acute

- to

- chronic ratio (ACR) to extrapolate the chronic value for the
most acutely sensitive fish species. Effects data for fish are generally used as surrogate data for amphibians. When amphibian data is available it is used within the risk assessment. For triclosan because it can exist in unionized and ionized states at environmentally relevant pHs (pKa is around 7.9

- 8.1), a relationship of toxicity with pH is desirable which means testing of the same species under different pH conditions. However as an alternative, studies conducted under pH conditions that optimize the unionized state, which is generally considered the more bioavailable and toxic state, would be conservatively used to represent toxicity at higher more alkaline conditions under which the ionized form would dominate.

A rainbow trout (cold water species) and a fathead minnow (warm water species) study with technical grade triclosan were submitted to the a gency to support registration (Table 25) . Both studies are classified as Supplement al information. The rainbow trout study was originally classified as an Acceptable study but upon further examination of the stability of triclosan it declined by over 50% during the exposure period which is not sufficiently stable. From other similar st udies triclosan needs frequent replacement such as flow

- through conditions to ensure stable exposure concentrations. Values based on nominal or average measured concentrations potentially underestimate sensitivity to triclosan.

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Page 84 of 130 There are several acute fre shwater fish and amphibian studies in the open literature, a preliminary list of public literature obtained by the Office of Water and provided to AD is provided in Table 26

. The a gency has started but not completed the review of these data for use in per forming the risk assessment. As discussed in Section 4.4 Effects Analysis Plan, a search of the public literature for triclosan effect studies and a review of the relevant studies found is planned as part of the risk assessment phase. There are a limited number of open literature studies that have been reviewed at this point. Public literature that has previously been reviewed are studies looking at endocrine effects using Japanese medaka, a non

- native North American species and these results are summari zed in Table 25 . In the Foran, Bennett, and Benson (2000) study the control results are not reported and without this information the study quality cannot be verified and is therefore Unacceptable at this time. In the other reviewed study, Ishibashi et a l (2004), the reported triclosan concentrations were not sufficiently stable (decline >30%) over the renewal period. Acute toxicity values range for the Supplemental studies from 260 μg ai/L for the fathead minnow ( Pimephales promelas ) to 602 μg ai/L for the Japanese medaka. While there is uncertainty in the use of this data because of the instability of triclosan, the measured concentrations at the end of the renewal period can be used to provide a reasonable lower bound so at this time no additional acu te data is being required.

A number of the studies in the open literature in Table 26 are identified as conducted under static conditions with no analytical measurements of triclosan concentrations and are therefore not suitable for use in a risk assessmen t.

Three additional acute studies were conducted with a triclosan formulation, Issue Plus II, one study with Zebrafish which was found to be Unacceptable and one study each with rainbow trout and bluegill sunfish.

No chronic data have been submitted by the registrant. There are several early life stage freshwater fish studies in the open literature, a preliminary list of public literature obtained by the Office of Water and provided to AD is provided in Table 28

. The agency has started but not completed t he review of these data for use in performing the risk assessment

. In this case to establish chronic toxicity, a fish full life cycle test is used to address endocrine effect concerns on reproduction.

As discussed in Section 4. 4 , the Effects Analysis Pl an, a search of the public literature for triclosan effect studies and a review of the relevant studies found is planned as part of risk assessment phase of registration review. There are two open literature studies looking at the potential for endocrine effects that have been reviewed and these are listed in Table 27 . Both studies were conducted using Japanese medaka ( Oryzias latipes ). The first study reported was with Japanese 2 day post

- hatch medaka fry ( Oryzias latipes ) which were exposed for 14 days to triclosan (1, 10, 100 ppb) (Foran, Bennett, and Benson, 2000). While there was a solvent control included in the experimental design there was no negative control so effects of the solvent on study results cannot be dis counted. No significant effects on sex ratio or on female phenotypic sex characteristics as measured by sexually dimorphic fin shape and size were observed up to the

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Page 85 of 130 highest concentration tested, 100 ppb (nominal). There was a significant increase in fin size in males at the highest concentration tested. Foran, Bennett, and Benson (2000) concluded that while there was no statistically significant effect on sex ratio there appeared to be a weak trend of increasing males with increasing triclosan concentra tion and taken with the increased male fin length at the highest concentration suggested that triclosan could be weakly anti

- estrogenic/ androgenic. There are statistical tests that can better evaluate the existence of a trend than the tests used. The da ta in the journal article are insufficient to independently conduct such an analysis. Additionally triclosan was toxic at 100 ppb, significantly reducing the number of animals as compared to lower treatment levels. The later work with mature Japanese med aka by Ishibashi et al . (2204) also showed that triclosan has high toxicity on the early life stages (100% mortality (96

- h LC 50 

### 399 ppb, nominal; NOAEC for 156 ppb for hatching success and time

- to

hatch). When the medaka were exposed to triclosan at 20, 1 00 and 200 ppb nominal (8.3, 46.4, 112 ppb average measured concentrations, respectively, prior to renewal at 24 hours), there was a significant reduction in the length of F 0 

### females relative to control. A metabolite of triclosan may be a weak estrogenic compound with the potential to induce vitellogenin in male medaka but with no adverse effect on reproductive success and offspring (Ishibashi, et. al ., 2004). None of the studies are full life cycle tests and a fish full life cycle study is expected to be required.

Freshwater Invertebrates

- Triclosan

For triclosan, material preservative uses, an acute and chronic toxicity study with Daphnia

magna or Daphnia pulex using the TGAI, is used to establish the toxicity of triclosan to freshwater invertebrates . Th ree acute studies with D. magna using technical triclosan (>98% ai) have been submitted. One of the studies upon review was classified as unacceptable because measured triclosan concentrations were highly erratic and therefore actual exposure concentratio ns were not evident (MRID 42322102)

. The other two studies are classified as supplemental (MRID 43046002 and 43740701). Both of these two studies were conducted as static tests. Because in one of these studies triclosan was not measured at all treatment levels, a definitive EC 50 

### could not be reasonably determined (MRID 43740701). For this study the test only establishes a 48

- h EC 50 

### as >139 ppb ai from measured data, which is not an acceptable limit

test ( i.e ., >100,000 ppb ai or limit of triclosan solub ility whichever is lower). In the remaining study (MRID 43046002)

, ) measured concentrations showed triclosan was not stable and while a 48

- h EC 50 

### of 390 ppb ai based on nominal concentrations was reported

, use of this value will underestimate sensitivity and risk. A value based on measured data will be developed from the data and used within the assessment unless alternative data from the open literature is found to be acceptable and more sensitive. The data categorize the TGAI (99.7% ai) as being highly toxic to invertebrates (48

- h EC 50 

### = 390 μg ai/L).

There is no acceptable chronic data submitted for invertebrates. A life cycle study is expected to be required

.

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Page 86 of 130 For triclosan because it can exist in un

- ionized and ionize d states at environmentally relevant pHs (pKa is around 7.9

- 8.1), a relationship of toxicity with pH is desirable which means testing of the same species under different pH conditions. However as an alternative, studies conducted under pH conditions that optimize the unionized state, which is generally considered the more bioavailable and toxic state, would be conservatively used to represent toxicity at higher more alkaline conditions under which the ionized form would dominate.

Table 26

- Acute Toxicity of Triclosan to Aquatic Animals from Submitted Studies and Reviewed Open Literature

Species % Purity Test Type/ Temp/

pH/ Hardness

or Salinity b Endpoint (ug ai/L) a Toxicity Category Study Classification/ Source/ Comments

FRESHWATER

Fathead minnow ( Pimephales promelas ), 0.04 g, 15 mm Triclosan 99.7% S, U/ 22

o C/ 7.5 / 46 96

- h LC 50 = 260 96

- h NOAEC = 100 Highly toxic Supplemental Bowman, 1990, 1994 MRID 43046001 and 43295601/ Triclosan concentration were not measured

Rainbow Trout ( Oncorhynchus mykiss ), 0.44 g, 34 mm Triclosan 99.3% S, M/ 12

o C/ 6.8

– 8.1/ 130

- 160 96

- h LC 50 = 288

96

- h NOAEC = 100 Probit Slope = NA Highly toxic Supplemental/ Sword et al ., 1996 MRID 43969301/ Triclosan concentrations were not stable throughout the test

Japanese medaka ( Oryzias latipes ), 2 day post

- hatch fry 

### Triclosan pharma

ceutical grade %
NR SR/ 25 o C/

NR/ NR 48

- h LC 50 = 352 Highly toxic Unacceptable Foran, Bennett, Benson 2000 Control results were not

reported, insufficient

raw data provided to independently evaluate result, spread between concentrations is too large, solvent concentration not reported

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Page 87 of 130 Species % Purity Test Type/ Temp/

pH/ Hardness

or Salinity b Endpoint (ug ai/L) a Toxicity Category Study Classification/ Source/ Comments

Japanese medaka ( Oryzias latipes ), <24

- hr

post

- fertilized embryos Triclosan >98.0% SR, M/ 25 o C/

NR/ NR 96

- h LC 50 = 399 (nominal) Highly toxic Supplemental Ishibashi et al ., 2004 Triclosan concentrations

were not sufficiently stable over the renewal

period, not clear if nominal or measured values were used but believe nominal, pH not reported, solvent concentration too high

Japanese medaka ( Oryzias latipes ), 24

- hr

old larvae Triclosan >98.0% S, M/ 25 o C/

NR/ NR 96

- h LC 50 = 602 (nominal) Highly toxic Supplemental Ishibashi et al ., 2004 Triclosan concentrations

were not sufficiently stable over the renewal

period, not clear if nominal or measured values were used but believe nominal, pH not reported, solvent concentration too high

Rainbow Trout ( Oncorhynchus mykiss) , 2 g Triclosan (Issue Plus II) 3.89% S, U/ 17

o C/ 6.3

– 6.8 /NR 96

- h LC 50 = 910 (96

- h LC 50 = 23,400 f)

96

- h NOAEC = 700 (96

- h NOAEC = 18,000 f)

Probit Slope = 13.303 ai basis Highly

toxic Supplemental/ Terrell, 1988a MRID 41008912/ Acceptable formulation test for a spray drift event but triclosan would not be expected to be stable under

these exposure

conditions

Bluegill sunfish ( Lepomis macrochirus ), 2 g Triclosan (Issue Plus II) 3.89% S, U/ 22 o C/

NR/ NR 96

- h LC 50 = 1,450 (96

- h LC 50 = 37,200 f)

96

- h NOAEC = 18,000 (96

- h NOAEC = 700 f)

Probit Slope = 7.794 ai basis Moderatel

y toxic Supplemental/ Terrell, 1988b MRID 41008913/ Acceptable formulation

test for a spray drift event but triclosan would not be expected to be stable under these

exposure conditions

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Page 88 of 130 Species % Purity Test Type/ Temp/

pH/ Hardness

or Salinity b Endpoint (ug ai/L) a Toxicity Category Study Classification/ Source/ Comments

Zebrafish ( Brachydanio rerio ), 127 days old, 0.24 g, 30 mm Triclosan (Issue Plus II) 3.89% S, M/ 21.4

- 24.1 o C/ 7.8

– 8.4/ NR -- -- Unacceptable/ Bottcher, 1990 MRID 42322101 Triclosan concentrations

not stable throughout study, no solvent control

Water flea ( Daphnia
magna ), <24 h old Triclosan 99.7% S, M/ 20

- 21

o C/ 7.9

– 8.5/ 160 48

- h EC 50 = 390

48

- h NOAEC = 100 Highly toxic Supplemental/ Forbis and Muckeman, 1990 MRID 43046002/ Nominal concentrations,

triclosan measured but results highly erratic, shown not to be stable in

some studies, at study pH conditions > half would be in an ionized form versus the more bioavailable nonionized
state

Water flea ( Daphnia
magna ), <24 h old Triclosan >99.0% S, M/ 19.5

– 22.4 o C/ 8.2

– 8.9/

256

– 278 c 48

- h EC 50 > 139 Supplemental Wuthrich, 1990b MRID 43740701/ triclosan analytical confirmation design was inadequate, stability not demonstrated, does not

meet conditions for a limit test and does not

result in a definitive EC 50 value

Water flea ( Daphnia
magna ), <24 h old Triclosan Technical S, M/ 20.0

– 20.5 o C/ 8.0

– 8.4/ NR -- -- Unacceptable/ Wuthrich, 1990a MRID 42322102/ Measured concentrations were highly erratic

therefore actual exposure concentration unknown

Water flea ( Daphnia
magna ), <24 h old Triclosan (Issue Plus II) 3.89% S, U/ NR/ NR/ NR 48

- h EC 50 = 16.3 (48

- h EC 50 = 420 f)

48

- h NOAEC = 9.34 (48

- h NOAEC = 240 f) Highly toxic Supplemental/ Terrell, 1988c MRID 41008914/ lack of pH and DO measurements, triclosan not measured

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Page 89 of 130 Species % Purity Test Type/ Temp/

pH/ Hardness

or Salinity b Endpoint (ug ai/L) a Toxicity Category Study Classification/ Source/ Comments

Water flea ( Daphia
magna ), egg

carrying adults of various ages (first offspring were discarded) Pharma

ceutical grade Triclosan % NR SR, U/ 25 o C/

8.4/ NR 6

- d LC 50 > 100 ppb

6

- d NOAEC > 100 ppb (survival and length of

adults and neonates, ephippium production, fecundity, and proportion of male broods produced) Unacceptable Flaherty and Dodson 2005 Control results were not provided, triclosan was not measured, water not frequently enough given

its instability. only 3 concentrations were tested and spacing is that

of a range

- finding test (1, 10, and 100 ppb). f = formulation; S = Stat ic; SR = static renewal; SS = spiked sediment; M = measured concentration; NA = Not applicable; NR = not reported; U = unmeasured, nominal concentrations

a Except where noted in the table.

b Water hardness as mg/L calcium carbonate (CaCO 3 ) for freshwater t ests and salinity as parts per thousand (ppt) for estuarine/marine tests.

c Converted from the German degrees hardness (dH) value to U.S. units, where 1 dH = 17.8 mg/L CaCO 3 . 

### Table 27

- Acute Toxicity of Triclosan to Aquatic Animals from Open Literature Provided by OW

Species Method 1 Chemical Purity Endpoint pH Effect Conc. (μg/L) Reference/ Comments

FRESHWATER Cladoceran (<24 hr), Ceriodaphnia dubia R, M ≥96.1% 48

- h EC 50 6.8

- 7.0 130* (120* union.) Orvos et al. 2002/ fed Cladoceran (<24 hr), Ceriodaphnia dubia R, M ≥96.1% 48

- h EC 50 7.4

- 7.6 175* (140* union.) Orvos et al. 2002/ fed Cladoceran (<24 hr), Ceriodaphnia dubia R, M ≥96.1% 48

- h EC 50 8.0

- 8.2 235* (130* union.) Orvos et al. 2002 fed Cladoceran (<24 hr), Ceriodaphnia dubia R, M ≥96.1% 48

- h EC 50 8.2

- 8.5 410* (115* union.) Orvos et al. 2002 fed

Cladoceran (<24 hr), Daphnia magna R, M ≥96.1% 48

- h EC 50 390 Orvos et al. 2002* AD believes study is the same as MRID

43046002 Cladoceran, Daphnia magna S, U

- 48

- h EC 50 260 Harada et al. 2008
Crustacean (<24 hr), Thamnocephalus platyurus 96

- h LC 50 - 470 Kim et al. 2009 Excessive solvent
Rainbow Trout, Oncorhynchus mykiss 96

- h LC 50 350 Ciba 1998**

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Page 90 of 130 Species Method 1 Chemical Purity Endpoint pH Effect Conc. (μg/L) Reference/ Comments

Fathead minnow, Pimephales promelas S, U ≥96.1% 96

- h LC 50 260 Orvos et al. 2002 AD believes study is the same submitted as MRID 43046001 Bluegill, Lepomis macrochirus S, U ≥96.1% 96

- h LC 50 370 Orvos et al. 2002
Japanese medaka (adult), Oryzias latipes R, U 96

- h LC 50 1700 Nassef et al. 2009

Japanese Medaka (2dph), Oryzias latipes 48

- h LC 50 - 352 Foran et al. 2000 Duration insufficient
Japanese Medaka (24hpf), Oryzias latipes 96

- h LC 50 - 399 Ishibashi et al. 2004 Excessive solvent
Japanese Medaka (24 hr), Oryzias latipes 96

- h LC 50 - 602 Ishibashi et al. 2004 Excessive solvent
Japanese Medaka (24 hr), Oryzias latipes 96

- h LC 50 - 600 Kim et al. 2009 Excessive solvent
Zebrafish (embryos), Danio rerio S,U ≥97% 96

- h LC 50 7.0 420 Oliveira et al. 2009
Zebrafish (adults), Danio rerio R,U ≥97% 96

- h LC 50 7.0 340 Oliveira et al. 2009
Southern leopard frog (Gosner stage 30), Rana sphenocephala S,U

- 96

- h LC 50 - 562 Palenske 2009

Southern leopard frog (Gosner stage 36), Rana sphenocephala S,U

- 96

- h LC 50 - 476 Palenske 2009

Woodhouse’s toad (Gosner stage 30), Bufo woodhousii woodhousii S,U

- 96

- h LC 50 - 152 Palenske 2009

Woodhouse’s toad (Gosner stage 36), Bufo woodhousii woodhousii S,U

- 96

- h LC 50 - 433 Palenske 2009

Blanchard’s cricket frog (Gosner stage 22), Acris crepitans blanchardii S,U

- 96

- h LC 50 - 265 Palenske 2009

Blanchard’s cricket frog (Gosner stage 30), Acris crepitans blanchardii S,U

- 96

- h LC 50 - 367 Palenske 2009

South African clawed frog, Xenopus laevis S, U

- 96

- h EC 50 820 Harada et al. 2008

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South African clawed frog (Gosner stage 22), Xenopus laevis S,U

- 96

- h LC 50 - 343 Palenske 2009

South African clawed frog (Gosner stage 30), Xenopus laevis S,U

- 96

- h LC 50 - 259 Palenske 2009

South African clawed frog (Gosner stage 36), Xenopus laevis S,U

- 96

- h LC 50 - 443 Palenske 2009

South African clawed frog (Gosner stage 46), Xenopus laevis S,U

- 96

- h LC 50 - 664 Palenske 2009

SALTWATER Brown mussel (embryo), Perna perna S, U

- IC 50 7.87

- 8.03 Sl=35ppt 135 Cortez et al. 2012

Brown mussel (sperm), Perna perna S, U 60 min IC 50 7.87

- 8.03 Sl=35ppt 490 Duration insufficient Effect measured fertilization inhibition

1 F = flowthrough; R = static renewal; S = static; M = measured concentrations used; U = unmeasured (nominal) concentrations used; Sl = salinity * Estimated from Figure 3 found in Orvos et al. 2002. **Reported in Palenske 2009. ( i.e. , total triclosan versus unionized (union) triclosan).



### Table 28

- Chronic Toxicity of Triclosan to Aquatic Animals from Submitted Studies and Reviewed Open Literature

Species % Purity Test Type/ Temp/ pH/ Hardness or Salinity a Endpoint (ug ai/L) a Study Classification/ Source/ Comments

FRESHWATER

Japanese medaka ( Oryzias latipes ), <24 h post

fertilized embryos Triclosan >98.0% SR, M/ 25 o C/

NR/ NR ELS NOAEC = 156 (nominal) (time

- to

- hatch, hatching success) Supplemental Ishibashi et al ., 2004 Triclosan concentrations were not sufficiently stable over the renewal period; growth of surviving larvae

was not determined

- insufficient exposure duration for growth and survival endpoints in an early life

stage guideline study, nominal concentrations used rather t han measured

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Page 92 of 130 Species % Purity Test Type/ Temp/ pH/ Hardness or Salinity a Endpoint (ug ai/L) a Study Classification/ Source/ Comments

Japanese medaka ( Oryzias latipes ), mature, 300 mg, 30 mm Triclosan >98.0% SR, M/ 25 o C/

NR/ NR 21

- d NOAEC = 46.3 c (female F 0 total length)

NOEC > 112 c (F 0 body weight, female EROD and PROD activity,

number fecundity, fertility, F 1 time

- to

- hatch, last 24 h F 1 group

additional 90

- d survival, total length, body weight, sex ratio)

Significant decrease in hatching success at 8.3 c ppb but not at 46.3 c or 112 c ppb

21 d parental exposure, 90 d observation of hatched larvae collected from last 24 hr exposure

period, embryos were removed after fertilization and maintained in control water Supplemental Ishibashi et al ., 2004 Triclosan concentrations were not sufficiently stable over the renewal period; pH not reported, insufficient exposure (embryos not exposed)

Japanese medaka (Oryzias latipes), 2 day post

- hatch fry Triclosan pharma

ceutical grade %

NR SR, U/ 25 o C 14 day
exposure, 27 o C post/ NR/ NR NOEC > 100 (sex ratio)

NOEC = 10 (male fin length)

(Minimum significant difference (MSD) in proportion of change in

sex ratio was not provided or discussed) Supplemental Foran, Bennett, Benson 2000 14 days exposure 28 days post

- exposure triclosan was not measured, no negative control was included only a solvent control, unknown MSD, insufficient exposure duration and endpoints for a guideline fish early life stage study

Water flea (Daphnia magna), <24 h old Triclosan >99.0% SR, M/ 19.5

– 22.4

o C/ 8.2

– 8.9/ NR 21

- d NOEC < 139 Parent survival, hatch success and survival Supplemental/ MRID 437407

- 01 Growth not measured as a chronic endpoint, daily temperature unknown, triclosan analytical confirmation design was inadequate, stability not demonstrated

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Page 93 of 130 Species % Purity Test Type/ Temp/ pH/ Hardness or Salinity a Endpoint (ug ai/L) a Study Classification/ Source/ Comments

Water flea (Daphnia magna), 1st instar Pharma

ceutical

grade Triclosan

% NR SR, U/ NR/ NR NR Significant increase in production of males in first brood, 72% over 31% in controls at 10 ppb

32

- d NOEC >100 ppb survival and length of adults, survival of neonates, fecundity Unacceptable Flaherty and Dodson 2005 Control results were not provided, triclosan was not measured, specific concentrations tested were

not reported, water not refreshed frequently enough (renewed every 3 days) given triclosan instability, raw data insufficient for independent verification of results. NOAEC not provided, dose

response unkown. Production of males in control in standard life cycle test invalidates the study.

a Water hardness as mg/L calcium carbonate (CaCO 3 ) for freshwater tests and salinity as parts per thousand (ppt) for

es tuarine/marine tests.

b GSI: gonadosomatic index; HSI: heptosomatic index; VTG: vitellogenin

c Based on mean measured concentrations taken at 24 h prior to renewal



### Table 29

- Chronic Toxicity of Triclosan to Aquatic Animals from Open Literature Provided by OW

Species Test Type Chemical (% purity) pH Chronic Limits (NOAEC

- LOAEC) ( μ g/L) Reference/ Comments

FRESHWATER

Cladoceran, Ceriodaphnia dubia LC ≥96.1% 7.0 6

- 12 (total) Reproduction (5.6

- 11.2 union.) Orvos et al. 2002

Cladoceran Ceriodaphnia dubia LC ≥96.1% 8.5 182

- 344 Reproduction (51.8

- 97.9 union.) Orvos et al. 2002

Cladoceran Ceriodaphnia dubia LC ≥96.1% 7.0 50

- 108 Survival Orvos et al. 2002

Cladoceran (<24 hr), Ceriodaphnia dubia LC ≥96.1% 8.5 339

- >339 Survival Orvos et al. 2002

Cladoceran, Daphnia magna LC ≥96.1% 8.2

- 8.6 40

- 200 Reproduction (18

- 88 union.) Orvos et al. 2002

Rainbow trout, Oncorhynchus mykiss ELS ≥96.1% 8.2 34.1

- 71.3 Survival (15.1

- 31.6 union.) Orvos et al. 2002

Northern leopard frog, Rana pipiens ELS

- 23

- 230 Survival Fraker and Smith 2004

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Page 94 of 130 Species Test Type Chemical (% purity) pH Chronic Limits (NOAEC

- LOAEC) ( μ g/L) Reference/ Comments
Northern leopard frog Rana pipiens ELS

- 230

- >230 Growth Fraker and Smith 2004

North American bullfrog Rana catesbeiana ELS ≥ 97% 7.7 1.2

- 16.6 Growth Veldhoen et al. 2006
S. African clawed frog, Xenopus laevis 21 d 7.0

- 7.3 32.3

- >32.3 Survival and growth Fort et al. 2010

ELS = early life stage; LC = full life cycle MATC = maximum allowable toxicant concentration which is the geometric mean of the NOAEC and LOAEC



### Table 30

- Toxicity of Triclosan to Sediment Benthos from Submitted Studies

Species % Purity Test Type/ Temp/ pH/ Hardness or Salinity b Endpoint (ug ai/L) a Study Classification/ Source/ Comments

Chironomus riparius, midge, 2

- 3 day old

- 1st instar larvae Triclosan 95% 14C

99.6% SS, S, M/ NR/ NR/ NR 28

- d NOAEC > 100 mg/kg

sediment (Survival, Emergence Ratio, Development Rate) Supplemental MIRD 475866

- 01 Developmental study. No growth
measurements (length/weight) made on the larvae

, no reproduction effect
measurements



### Estuarine/Marine Fish and Invertebrates

- Triclosan

For triclosan, material preservative uses, an acute toxicity study with an estuarine/marine fish, a mollusk 22 

### , and a shrimp 23 

### and a chronic test with the shrimp using the TGAI are used to establish the toxicity of triclosan to estuarine/marine animals. To establish a saltwater ACR, the acute shrimp value is divided by its chronic value. No acute or chronic toxicity data have been

su bmitted for estuarine/marine fish. In a preliminary list of public literature obtained from the Office of Water and provided to AD ( Table 26 ), no estuarine/marine fish or shrimp data are listed. There is one acute mollusk study. The study will be review ed as part of the risk assessment phase of registration review. An acute mollusk and mysid (shrimp) study were held in reserve in the RED

. A chronic test with the mysid is expected to be required for registration review.

In the interim, w here acute data for saltwater fish and mysid were missing, values were modeled using Web

- ICE (see Appendix E ) and ECOSAR as alternative sources of data. Web

- ICE v3.1 

### results were considered the most reasonable and result in estimates of a 96

- h LC 50 

### of 716 ppb f or Sheepshead minnow ( Cyprinodon variegatus ) and a 96

- h LC 50 

### of 1 52 ppb for the mysid, Americamysis bahia

.

22 Embryo

- larvae or shell deposition
23 Penaeidae or Mysidacea

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Page 95 of 130 Benthic Invertebrates

For triclosan, material preservative uses, chronic s ediment toxicity studies are used because triclosan and methyl

- tr iclosan are expected to adsorb to aquatic sediments (K oc 

### = 8417

- 23,380 ml/g) and the half

- life in sediment is greater than ten days . One developmental study ( MRID 47586601 ) but no chronic reproduction study has been submitted for triclosan. No adverse impacts on midge larva emergence or development rate occurred at sediment concentrations up to 100 mg ai/kg sediment

. Chronic testing is required for three species, two freshwater species (a midge and an amph ipod ( Hyallela azteca ) and an estuarine/marine amphipod). These studies were already required as part of the post

- RED DCI (GDCI 054901

- 30197 Docket EPA

- HQ

OPP

- 2007

- 0513

- 0066) and n o sediment testing in addition to these is anticipated to be required for r egistration review

. Aquatic Plants

For triclosan, material preservative uses, testing with four nonvascular species (a freshwater diatom 24 

### , a marine diatom 25 

### , a green algae 26 

### , and a cyanobacterium 27 

### ) and one vascular species (duckweed) using TGAI are used to establish toxicity of triclosan to aquatic plants. ). The registrant submitted an acceptable duckweed ( L. gibba ) study and three acceptable nonvascular species studies (freshwater diatom, Navic ula pelliculosa ; marine diatom, Skeletonema costatum ; blue

- green algae, Anabaena flos

- aquae ) but did not submit an acceptable green algae (Pseudokerscheneria subcapitatum [formerly Selanastrum capricornutum ]) study. However, acceptable green algae ( Scened esmus subspicatus ) data was obtained from open literature Orvos et al. ( 2002). Collectively these studies indicate that nonvascular aquatic p lants, especially green algae (I C 50 

### = 0 .7 μg ai/L) and cyanobacteria (I C 50 

### = 1.2 μg ai/L) are highly suscep tible to triclosan. Duckweed (I C 50 

### >62.5 μg ai/L) is much less susceptible than algae. No additional aquatic plant data are expected to be needed for triclosan.

Table 31

- Toxicity of Triclosan to Aquatic Plants from Submitted Studies

Species % Purity Test Type/ Temp/ pH/ Hard b Endpoint (ug ai/L) Study Classification/ Source/ Comments Pseudokirchneriella subcapitata , Green algae (or Raphidocelis subcapitata ) 99.5 S 96

- h IC 50 = 3.4 ppb NOEC = 2.5 ppb Acceptable MRID 444228

- 01

24 Navicula pelliculosa
25 Skeletonema costatum
26 Pseudokerscheneria subcapitatum [formerly Selanastrum capricornutum ]
27 Anabaena flos

- aquae

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Page 96 of 130 Species % Purity Test Type/ Temp/ pH/ Hard b Endpoint (ug ai/L) Study Classification/ Source/ Comments Anabaena flos

aquae , freshwater cyanobacteria 99.5 S 96

- h IC 50 = 1.2 ppb NOEC < 0.5 ppb Acceptable MRID 444228

- 01

Navicula pelliculosa

, freshwater diatom 99.5 S 96

- h IC 50 = 16 ppb NOEC < 0.5 ppb Acceptable MRID 444228

- 01

Skeletonema

costatum , Marine diatom 99.5 S 96

- h IC 50 > 66 ppb NOEC < 12 ppb Acceptable MRID 444228

- 01

Lemna gibba

, Duckweed 99.5 S 7

- d IC 50 > 62.5 ppb NOEC < 12,5 ppb Acceptable MRID 444228

- 01



### Table 32

- Toxicity of Triclosan to Aquatic Plants from Open Literature Reviewed by OW

Species Purity Method
1 Study Duration

(days) Effect Measured pH NOEC (μg/L) LOEC (μg/L) ICx (μg/L) Reference

FRESHWATER

Green alga Closterium ehrenbergii >97% S, U 4 Growth rate (asexual reproduction) 7.5 250 500 Ciniglia et al. 2005

Green alga Closterium ehrenbergii >97% S, U 4 IC 50 Growth rate (asexual reproduction) 7.5

- - 620 Ciniglia et al. 2005

Green alga Closterium ehrenbergii >97% S, U 4 Zygospore production (sexual reproduction) 7.5 625 937.5 Ciniglia et al. 2005 Green alga Pseudokirchneriela subcapitata ≥96.1% S, U 4 IC 25 (growth) 7.3

- 7.7 - - 2.44 Orvos et al. 2002
Green alga Pseudokirchneriela subcapitata ≥96.1% S, U 4 IC 50 (growth) 7.3

- 7.7 - - 4.46 Orvos et al. 2002
Green alga Pseudokirchneriela subcapitata - S, U 4 IC 50 (growth) - - - 12 Harada et al. 2008
Green alga, Pseudokirchneriella subcapitata Analyti

cal grade S, U 3 IC 25 (Growth) - - - 3.4 Tatarazako et al. 2004
Green alga Pseudokirchneriella subcapitata Analyti

cal grade S, U 3 IC 50 (Reduced growth) - - - 4.7 Tatarazako et al. 2004
Green alga, Pseudokirchneriella subcapitata 98% S, U 3 IC 50 (growth) (biomass via optical density) 7.7

- 8.7 0.53 Yang et al. 2008

Green alga, Pseudokirchneriella subcapitata 98% S, U 3 Growth Inhibition (biomass via optical density) 7.7

- 8.7 0.20 0.40 Yang et al. 2008

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Page 97 of 130 Species Purity Method
1 Study Duration

(days) Effect Measured pH NOEC (μg/L) LOEC (μg/L) ICx (μg/L) Reference

Green alga Pseudokirchneriela subcapitata 99.5% S, U 3 IC 50 (growth

- biomass via

optical density) 7.0

- - 2.50 Yang et al. 2011
Green alga Scenedesmus S ubspicatus ≥96.1% S, M 4 IC 50 (growth

- biomass) 7.5

- 7.8 - - 0.7 Orvos et al. 2002
Green alga Scenedesmus S ubspicatus ≥96.1% S, M 4 Growth

– biomass 7.5

- 7.8 0.5 1.2 Orvos et al. 2002
Green alga Scenedesmus S ubspicatus ≥96.1% S, M 4 IC 50 (growth

- biomass) 7.5

- 7.8 - - 1.4 Orvos et al. 2002
Green alga Scenedesmus S ubspicatus ≥96.1% S, M 4 Growth

– biomass 7.5

- 7.8 0.69 1.5 Orvos et al. 2002
Green alga Scenedesmus S ubspicatus ≥96.1% S, M 3 IC 50 (growth rate) 7.5

- 7.8 - - 2.8 Orvos et al. 2002
Green alga Scenedesmus S ubspicatus ≥96.1% S, M 3 Growth rate 7.5

- 7.8 0.5 1.2 Orvos et al. 2002
Green alga Scenedesmus vacuolatus 99.8% S, U 1 IC 50 (reproductive inhibition) < 7.0 1.9 Franz et al. 2008

Blue

- green alga Anabaena flos

aquae ≥96.1% S, M 4 IC 25 (growth) 7.5

- - 0.67 Orvos et al. 2002

Blue

- green alga Anabaena flos

aquae ≥96.1% S, M 4 IC 50 (growth) 7.5

- - 0.97 Orvos et al. 2002

Blue

- green alga Anabaena flos

aquae ≥96.1% S,U 4 IC 50 (growth

– biomass) 7.5

- - 1.6 Orvos et al. 2002

Blue

- green alga Anabaena flos

aquae ≥96.1% S,U 4 Growth

– biomass) 7.5 0.81 1.6 Orvos et al. 2002

Diatom Navicula pelliculosa ≥96.1% S, U 4 IC 25 (growth) 7.2

- 7.7 - - 10.7 Orvos et al. 2002
Diatom Navicula pelliculosa ≥96.1% S, U 4 IC 50 (growth) 7.2

- 7.7 - - 19.1 Orvos et al. 2002
Duckweed Lemna gibba ≥96.1% S, U 7 IC 25 and IC 50 (growth) 7.7

- 8.7 - - >62.5 Orvos et al. 2002 Duckweed Lemna minor >99% S, U 7 IC 50 (growth) - - - 26.3 Küster et al. 2007

SALTWATER

Diatom Skeletonema costatum ≥96.1% S, U 4 IC 25 and IC 50 (growth) 8.2

- 8.5 - - >66.0 Orvos et al. 2002

1 F = flowthrough; R = static renewal; S = static; M = measured concentrations used; U = unmeasured (nominal) concentrations used

2 MATC = maximum allowable toxicant concentration which is the geometric mean of the NOAEC and LOAEC

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Page 98 of 130 Table 33

- Other Chronic Data on the Effects of Triclosan on Aquatic Organisms from Open Literature Reviewed by OW

Species Purity Duration Effect Measured pH NOEC (μg/L) LOEC (μg/L) MATC (μg/L) Reference/ Comments PLANTS Green alga, Selenastrum sp. - 14 d Growth 7.8 10 >10 >10 Lawrence et al. 2009 Only 3 concs Green alga, Ulothrix sp. - 14 d Growth 7.8 10 >10 >10 Lawrence et al. 2009 Only 3 concs Green alga, Ankistrodesmus falcatus - 14 d Growth 7.8 100 >100 >100 Lawrence et al. 2009 Only 3 concs
Green alga Closterium ehrenbergii >97% 4 days Cell size and viability 7.5 250 500 353.6 Ciniglia et al. 2005 Endpoint
Green alga, Dunaliella tertiolecta - 4 day EC 50 (Growth

– cell density) - - - 3.55 DeLorenzo and Fleming 2008 Excessive solvent
Green alga, Dunaliella tertiolecta - 4 day Growth

– cell density - 1.6 4.9 2.8 DeLorenzo and Fleming 2008 Excessive solvent Green alga Scenedesmus S ubspicatus - 4 d ? ? 2.6 >2.6 >2.6 Ferrari et al. 2002 Details
Green alga Scenedesmus quadricauda - 14 d Growth 7.8 1 10 3.16 Lawrence et al. 2009 Only 3 conce

Diatom, Nitzchia palea 99.8% 24 hr EC 50 Photosynthesis

inhibition (biofilm) ≤ 7.0

- - 430 Franz et al. 2008 Biofilm

Diatom, Nitzchia palea 99.8% 24 hr EC 50 Photosynthesis

inhibition (suspension) ≤ 7.0

- - 390 Franz et al. 2008 Suspension

Diatom, Synedra sp. - 14 d Growth 7.8 100 >100 >100 Lawrence et al. 2009 Only 3 concs Duckweed, Lemna minor >99% 24 hr Fluorescence inhibition EC 50 1,692 Küster et al. 2007 Duration Macrophyte, Elodea canadensis >97% 72 hr Chlorophyll

- a 8.8

- 9.0 <3 3 <3 Heilman 2008 Duration Macrophyte, Potamogeton perfoliatus >97% 72 hr Chlorophyll

- a 8.8

- 9.0 300 3,000 948.7 Heilman 2008 Duration

Macrophyte, Eclipta prostrata - 28 d Growth

– biomass (fresh weight) - 8.9 55 22.12 Stevens et al. 2009 Deionized water as dilution
water Macrophyte, Sesbania herbacea - 28 d Growth

– biomass (fresh weight) - 55 396 147.58 Stevens et al. 2009 Deionized water as dilution
water Macrophyte, Bidens frondosa - 28 d Growth

– biomass (fresh weight) - 396 >396 >396 Stevens et al. 2009 Deionized water as dilution
water INVERTEBRATES Rotifer, Brachionus calyciflorus - 2 d NR

- 50 >50 >50 Ferarri et al. 2002
No Endpoint Zebra mussel (20 mm), Dreissena polymorpha 97% 96 hr Increased DNA damage 7.5 <0.29 0.29 <0.29 Binelli et al. 2009a Fed

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Page 99 of 130 Species Purity Duration Effect Measured pH NOEC (μg/L) LOEC (μg/L) MATC (μg/L) Reference/ Comments
Zebra mussel (20 mm), Dreissena polymorpha 97% 96 hr Destabilization of lysosomal membranes 7.5 0.58 0.870 0.71 Binelli et al. 2009a Fed
Midge (12 d), Chironomus dilutes ≥ 97% 10 d EC 50 , Growth 8.4

- - 280 Dussault et al. 2008 Excessive solvent Midge (12 d), Chironomus dilutes ≥ 97% 10 d EC 50 , Survival 8.4

- - 400 Dussault et al. 2008 Excessive solvent
Cladoceran (<24 hr), Ceriodaphnia dubia Analytical grade 7 days IC 25 Reproduction (Fecundity) 7.0

- 7.5 - - 170 Tatarazako et al. 2004 Unmeasured short

- term chronic test
Cladoceran (<24 hr), Ceriodaphnia dubia Analytical grade 7 days IC 50 Reproduction (Fecundity) 7.0

- 7.5 - - 220 Tatarazako et al. 2004 Unmeasured short

- term chronic test
Cladoceran, Ceriodaphnia dubia - 7 days NR (assumed survival and reproduction) - 4 >4 >4 Ferarri et al. 2002 No Endpoint

Cladoceran (adult with eggs), Daphnia magna Analytical grade 6 days LC 50 Survival 8.4 100 >100 >100 Flaherty and Dodson 2005 Duration; Unmeasured subchronic test Cladoceran (adult with eggs), Daphnia magna Analytical grade 6 days Growth (length) 8.4 100 >100 >100 Flaherty and Dodson 2005 Duration; Unmeasured subchronic test Cladoceran (adult with eggs), Daphnia magna Analytical grade 6 days Resting egg production 8.4 100 >100 >100 Flaherty and Dodson 2005 Duration; Unmeasured subchronic test Cladoceran (adult with eggs), Daphnia magna Analytical grade 6 days Fecundity 8.4 100 >100 >100 Flaherty and Dodson 2005 Duration; Unmeasured subchronic test

Cladoceran (adult with eggs), Daphnia magna Analytical grade 6 days Sex ratio (proportion of male broods produced) 8.4 100 >100 >100 Flaherty and Dodson 2005 Duration; Unmeasured subchronic test
Cladoceran (<24 hr), Daphnia magna Analytical grade 30 days LC 50 Survival 8.4 10 >10 >10 Flaherty and Dodson 2005 Unmeasured schronic test Cladoceran (<24 hr), Daphnia magna Analytical grade 30 days Growth (length) 8.4 10 >10 >10 Flaherty and Dodson 2005 Unmeasured chronic test Cladoceran (<24 hr), Daphnia magna Analytical grade 30 days Resting egg production 8.4 10 >10 >10 Flaherty and Dodson 2005 Unmeasured chronic test Cladoceran (<24 hr), Daphnia magna Analytical grade 30 days Fecundity 8.4 10 >10 >10 Flaherty and Dodson 2005 Unmeasured chronic test Cladoceran (<24 hr), Daphnia magna Analytical grade 30 days Sex ratio 8.4 1 10 3.162 Flaherty and Dodson 2005 Unmeasured chronic test Cladoceran (<24 hr), Daphnia magna ≥96.1% 21 days Survival

- 200 1000 447.2 Orvos et al. 2002 Unmeasured chronic test Amphipod (7

- 14 d), Hyalella azteca ≥ 97% 10 d LC 50 7.7

- - 200 Dussault et al. 2008 Excessive solvent Amphipod (7

- 14 d), Hyalella azteca ≥ 97% 10 d EC 50 , Growth 7.7

- - 250 Dussault et al. 2008 Excessive solvent
FISH Japanese medaka (24hpf), Oryzias latipes 98% 21 days Growth (females) - 60.8 136.9 83.24 Ishibashi et al. 2004 Excessive solvent
Japanese medaka (24hpf), Oryzias latipes 98% 14 days Decreased hatchability of fertilized eggs - - 313 313 Ishibashi et al. 2004 Excessive solvent
Japanese medaka (24hpf), Oryzias latipes 98% 14 days Time to hatching - - 313 313 Ishibashi et al. 2004 Excessive solvent

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Page 100 of 130 Species Purity Duration Effect Measured pH NOEC (μg/L) LOEC (μg/L) MATC (μg/L) Reference/ Comments Japanese medaka (24hpf), Oryzias latipes 98% 21 days Growth

- 136.9

- >136.9 Ishibashi et al. 2004 Excessive solvent
Japanese medaka (mature), Oryzias latipes 98% 21 days Increased hepatic vitellogenin - - 12.8 12.8 Ishibashi et al. 2004 Excessive solvent, endpoint
Japanese medaka (2 dph), Oryzias latipes - 14 days Dorsal and anal fin lengths - 10 100 31.62 Foran et al. 2000 Duration

Japanese medaka (2 dph), Oryzias latipes - 14 days Gender development

(sex ratio) - 100 >100 >100 Foran et al. 2000 Duration
Japanese medaka (eggs), Oryzias latipes Analytical grade 14 dph IC 25 Survival 7.0

- - 290 Tatarzako et al. 2004 Duration
Japanese medaka (eggs), Oryzias latipes Analytical grade 14 dph IC 50 Survival 7.0

- - 400 Tatarzako et al. 2004 Duration
Zebrafish (eggs), Danio rerio Analytical grade 9 dph IC 25 Survival 7.0

- - 160 Tatarzako et al. 2004 Duration Zebrafish (eggs), Danio rerio Analytical grade 9 dph IC 50 Survival 7.0

- - 220 Tatarzako et al. 2004 Duration
Zebrafish, Danio rerio - 10 dph NR (assume hatchability and survival) - 200 >200 >200 Ferarri et al. 2002 Duration
Zebrafish (embryos), Danio rerio ≥ 97% 72 hr Decreased hatchability 7.0 300 500 387.30 Oliveira et al. 2009 Duration
AMPHIBIANS
North American bullfrog (Gosner stage 31

- 33) Rana catesbeiana ≥97% 96 hr Reduced growth (Weight loss) 7.7 0.13 Veldhoen et al. 2006 Fed

North American bullfrog (Gosner stage 31

- 33) Rana catesbeiana ≥97% 11 days Increased hindlimb development 7.7 0.13 Veldhoen et al. 2006 Fed

North American bullfrog (Gosner stage 31

- 33), Rana catesbeiana >97% 18 days Hindlimb development 16.6 >16.6 >16.6 Veldhoen et al. 2006 Duration

North American bullfrog (Gosner stage 31

- 33), Rana catesbeiana >97% 11 days Abundance of TR α , TRß & PCNA mRNA 7.7 16.6 >16.6 > 16.6 Veldhoen et al. 2006 Duration; Endpoint
Southern leopard frog (Gosner stage 30) Rana catesbeiana - 96 hr Decreased metabolic rate - 280 561 396.33 Palenske 2009 Endpoint
Southern leopard frog (Gosner stage 30) Rana catesbeiana - 96 hr Increased heart
rate - 31 47 38.17 Palenske 2009 Endpoint, U

- shaped curve
Southern leopard frog (Gosner stage 36) Rana catesbeiana - 96 hr Decreased heart rate - 63 125 88.74 Palenske 2009 Endpoint
Northern leopard frog (Gosner stage 26), Rana pipiens - 24 days Activity level

- - 0.23 0.23 Fraker and Smith 2004 Duration; Endpoint

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Page 101 of 130 Species Purity Duration Effect Measured pH NOEC (μg/L) LOEC (μg/L) MATC (μg/L) Reference/ Comments Northern leopard frog (Gosner stage 26), Rana pipiens - 24 days Startle
response - 23 230 72.73 Fraker and Smith 2004 Duration; Endpoint Blanchard’s cricket frog (Gosner stage 22) Acris crepitans blanchardii - 96 hr Heart rate

- 375 >375 >375 Palenske 2009 Endpoint

Blanchard’s cricket frog (Gosner stage 30) Acris crepitans blanchardii - 96 hr Heart rate

- 375 >375 >375 Palenske 2009 Endpoint

Blanchard’s cricket frog (Gosner stage 30) Acris crepitans blanchardii - 96 hr Metabolic rate

- 367 >367 >367 Palenske 2009 Endpoint

American toad (Gosner stage 26), Bufo americanus - 14 days Increased activity level 8.5

- 230 230 Smith and Burgett 2005 Endpoint, high control

mortality (18.75%) Woodhouse’s toad (Gosner stage 30) Bufo woodhousii woodhousii - 96 hr Metabolic rate

- 152 >152 >152 Palenske 2009 Endpoint

Woodhouse’s toad (Gosner stage 30) Bufo woodhousii woodhousii - 96 hr Increased heart
rate - 31 47 38.17 Palenske 2009 Endpoint

Woodhouse’s toad (Gosner stage 36) Bufo woodhousii woodhousii - 96 hr Decreased heart rate - - 31 31 Palenske 2009 Endpoint

South African clawed frog (Gosner stage 22), Xenopus laevis - 96 hr Increased heart
rate - - 47 47 Palenske 2009 Endpoint, U

- shaped curve (decreased at 375)

South African clawed frog (Gosner stage 30), Xenopus laevis - 96 hr Increased heart
rate - 250 375 306.19 Palenske 2009 Endpoint

South African clawed frog (Gosner stage 36), Xenopus laevis - 96 hr Decreased heart rate - 63 94 76.95 Palenske 2009 Endpoint, U

- shaped curve

South African clawed frog (Gosner stage 36), Xenopus laevis - 96 hr Increased heart
rate - 250 375 306.19 Palenske 2009 Endpoint

South African clawed frog (Gosner stage 22), Xenopus laevis - 96 hr Metabolic rate

- 343 >343 >343 Palenske 2009 Endpoint, U

- shaped curve (decreased at 375)

South African clawed frog (Gosner stage 30), Xenopus laevis - 96 hr Metabolic rate

- 443 >443 >443 Palenske 2009 Endpoint

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Page 102 of 130 Species Purity Duration Effect Measured pH NOEC (μg/L) LOEC (μg/L) MATC (μg/L) Reference/ Comments South African clawed frog (Gosner stage 36), Xenopus laevis - 96 hr Metabolic rate

- 664 >664 >664 Palenske 2009 Endpoint, U

- shaped curve

South African clawed frog (Gosner stage 36), Xenopus laevis - 96 hr Decreased metabolic rate - - 130 130 Palenske 2009 Endpoint

South African clawed frog (male, 50

- 60 g), Xenopus laevis >98% 14 days Growth (weight) - 200 >200 >200 Matsumura et al. 2005 Duration; Unmeasured chronic

South African clawed frog (male, 50

- 60 g), Xenopus laevis >98% 14 days Growth (weight) - 200 >200 >200 Matsumura et al. 2005 Duration; Unmeasured chronic

South African clawed frog, Xenopus laevis - 21 days Survival, growth, and metamorph. 7.0

- 7.3 - 32.3 32.3 Fort et al. 2010 details



### Aquatic Organisms

- Methyl Triclosan

For methyl triclosan, a potential reaction product under certain environmental conditions, there is a lack of ecological toxicity data. There is one aquatic plant study for methyl

- triclosan and it shows methyl triclosan as being less toxic to algae than t he parent material. One study was also submitted for a daphnid . However, an EC 50 

### was not established because of the poor solubility of triclosan at concentrations exceeding 180 μg ai/L. No mortality or immobilization was observed at test concentrations less than or equal to 55 μg ai/L; one of 20 daphnids was reported to be immobile at the end of the 48

- h test at 180 μg ai/L. No chronic data are available. No methyl triclosan was detected in effluent from textile manufacturing and is therefore not consi dered a concern for the uses being assessed. Monitoring demonstrated a lack of methyl triclosan formed in effluent from textile plants; therefore, it is not considered a transformation product of concern at this time and n o additional data are expected to be required

.

Table 34

- Acute Toxicity of Methyl Triclosan to Aquatic Organisms from Open Literature Provided by OW

Species % Purity Test Type/ Temp/ pH/ Hard Endpoint (ug ai/L) Toxicity Category Study Classification/ Source/ Comments

Water flea ( Daphnia
magna ), <24 h old Methyl Triclosan

99.6% S, U/ 20 o C/ 7.8

– 7.9/ 250 48

- h EC 50 > 180 48

- h NOAEC > 180 Supplemental/ MRID 475866

- 03 Poor solubility, not measured, total not soluble concentration

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Page 103 of 130 Scenedesmus subspicatus

, freshwater green algae Methyl Triclosan S, M/ 23

– 24 o C/

8.0

– 8.9 72

- h IC 50 = 120 ppb

72

- h NOAEC = 40 ppb Supplemental/ MRID 475866

- 02 Several deviations with significant ones including: insufficient

exposure duration, insufficient vessel volume, species not a standard test species

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Page 104 of 130 

# APPENDIX D : Environmental Fate and Ecotoxicity Data for Appendices B and C

Adolfsson

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- 10): 1485

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Aranami, K. and J.W. Readman. 2007. Photolytic degradation of triclosan in freshwater and seawater. Chemosphere 66( 6): 1052

- 1056.

Balmer, M.E., T. Poiger, C. Droz, K. Romanin, P.A. Bergqvist, M.D. Muller and H.R. Buser. 2004. Occurrence of methyl triclosan, a transformation product of the bactericide triclosan, in fish from various lakes in Switzerland. Environ. Sci. T echnol. 38(2): 390

- 395.

Balmer, M.E., H. Buser, M.D. Muller and T. Poiger. 2005. Occurrence of some organic UV filters in wastewater, in surface waters, and in fish from Swiss lakes. Environmental Sci. Technol. 39(4): 953

- 962.

Barber, L.B., S.H. Keefe, R.C. Antweiler, H.E. Taylor and R.D. Wass. 2006a. Accumulation of contaminants in fish from wastewater treatment wetlands. Environ. Sci. Technol. 40(2): 603

- 611.

Barber, L.B., S.F. Murphy, P.L. Verplanck, M.W. Sandstrom, H.E. Taylor and E.T. Furlong. 2006b. Chemical loading into surface water along a hydrological, biogeochemical, and land use gradient: A holistic watershed approach. Environ. Sci. Technol. 40(2): 475

- 486.

Barnes, K.K., D.W. Kolpin, M.T. Meyer, M.E. Thurman, E.T. Furlong, S .D. Zaugg and L.B. Barber. 2002. Water

- quality data for pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999

- 2000. U.S. Geological Survey Open

- File Report 02

- 94.

Bätscher, R. 2006a. Methyl

- triclosan: Acute toxicity to Daphnia magna in a 48

- hour immobilization test. RCC Ltd. Environmental Chemistry & Pharmanalytics, Itlingen, Switzerland. Study Number A34931.

Bätscher, R. 2006b. Methyl

- triclosan: Toxicity to Scenedesmus subspicatus in a 72

- hour algal growth inhibition te st. RCC Ltd. Environmental Chemistry & Pharmanalytics, Itlingen, Switzerland. Study Number A34918. 448 Priority Existing Chemical Assessment Report No. 30.

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Page 105 of 130 Behera, S., S. Oh, and H. Park. 2010. Sorption of triclosan onto activated carbon, kaolinite and

m ontmorillonite: Effects of pH, ionic strength, and humic acid. Journal of Hazardous Materials 179 (684

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Bendz, D., N.A. Paxeus, T.R. Ginn and F.J. Loge. 2005. Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Hoeje River in Sweden. J. Hazard. Materials 122(3): 195

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Bester, K. 2005. Fate of triclosan and triclosan

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Binelli, A., D. Cogni, M. Parolini, C. Riva and A. Provini. 2009a. In vivo experiments for the evaluation of genotoxic and cytotoxic effects of triclosan in zebra mussel hemocytes. Aquat. Toxicol. 91(3): 238

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Binelli, A., D. Cogni, M. Parolini, C. Riva and A. Provini. 2009b. Cytotoxic and genotoxic effects of in vitro exposure to triclosan and trimethoprim on zebra mussel ( Dreissena polymorpha ) hemocytes. Comp. Biochem. Physiol. C. 150(1): 50

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Boyd, G.R., H. Reemtsma, D.A. Grimm and S. Mitra. 2003. Pharmaceuticals and personal care products (PP CPs) in surface and treated waters of Louisiana, USA and Ontario, Canada. Sci. Total Environ. 311(1

- 3): 135

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Boyd, G.R., J.M. Palmeri, S. Zhang and D.A. Grimm. 2004. Pharmaceuticals and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs) in stormwater canals and Bayou St. John in New Orleans, Louisiana, USA. Sci. Total Environ. 333(1

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Borgmann, U., D.T. Bennie, A.L. Ball and V. Palabrica. 2007. Effect of a mixture of seven pharmaceuticals on Hyalella azteca over multiple generations. Chemosphere. 66: 1278

- 1283.

Brain, R.A., M.L. Hanson, K.R. Solomon and B.W. Brooks. 2008. Aquatic plants exposed to pharmaceuticals: Effects and risks. Rev. Environ. Contam. Toxicol. 192: 67

- 115.

Brun, E.M., E. Bonet, R. Puchades and A. Maqui eira. 2008. Selective enzyme

- linked immunosorbent assay for triclosan. Application to wastewater treatment plant effluents. Environ. Sci. Technol: 42: 1665

- 1672.

Buth, J.M.; M. Grandbois; P.J. Vikesland; K. McNeill; W.A. Arnold. Aquatic photochemistry of chlorinated triclosan derivatives: potential source of poychlorodibenzo

- p

- dioxins. Environ. Toxicol. Chem

. 2009

, 2 8(12) , 2555

- 2563. MRID 49159301

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Page 106 of 130 Buth, J.M.; P.O. Steen; C. Sueper; D. Blumentritt; P.J. Vikesland; W.A. Arnold; K. McNeill. 2010. Dioxin photoproducts of triclosan and its chlorinated derivatives in sediment cores. Environ. Sci. Technol

. 4 4(1 2) , 4545

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Canesi, L., C. Ciacci, L.C. Lorusso, M. Betti, G. Gallo, G. Poiana and A. Marcomini. 2007. Effects of triclosan on Mytilus galloprovincialis hemocyte function and digestive gland enzyme activities: Possible modes of action on non target organisms. Comp. Bioch. Physiol. Part C: 145: 464

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Capdevielle M., R. Van Egmond, M. Whelan, D. Versteeg, M. Hofmann

- Kamensky, J. Inauen, V. Cunningham and D. Woltering. 2008. Consideration of exposure and species sensitivity of triclosan in the freshwater environment. Integ. Environ. Assess. Mgmt: 4(1): 15

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Carr, D.L., A.N. Morse, J.C. Zak, and T.A. Anderson. 20 11

. M icrobially Mediated Degradation of Common Pharmaceuticals and Personal Care Products in Soil under Aerobic and Reduced Oxygen Conditions. Water Air Soil Pollut. 216:633

- 642. MRID 49197202 Cha, J., and A. Cupples. 2010. Triclocarban and triclosan biode gradation at field concentrations and the resulting leaching potentials in three agricultural soils. Chemosphere 81(494

- 499).

Chalew, T.E.A. and R.U. Halden. 2009. Environmental exposure of aquatic and terrestrial biota to triclosan and triclocarban. J. A m. Water Resour. Assoc. 45(1): 4

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Chen, J., K.C. Ahn, N.A. Gee, S.J. Gee, B.D. Hammock and B.L. Lasley. 2007. Antiandrogenic properties of parabens and other phenolic containing small molecules in personal care products. Toxicol. Appl. Pharm. 221: 278

- 2 84.

Christensen, K. (1994) Triclosan

- Determination of Anaerobic Aquatic Biodegradation. Project Number: 93/12/5076. Unpublished study prepared by Springborn Laboratories Inc. 71 p. MRID 47261406

Christensen, K. (1994) Triclosan

- Aerobic Biodegradation in Water. Project Number: 93/4/4731. Unpublished study prepared by Springborn Laboratories Inc. 75 p. MRID 47261407

Ciba. 1998. Irgasan DP 300/Irgacare MP. Toxicological and ecological data. Ciba official registrations 2521. Ciba Specialty Chemicals I nc.
Ciniglia, C., C. Cascone, R.L. Giudice, G. Pinto and A. Pollio. 2005. Application of methods for assessing the geno

- and cytotoxicity of triclosan to C. ehrenbergii . J. Hazard. Materials. 122: 227

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Coogan, M.A. and T.W. LaPoint. 2008. Snail bioacc umulation of triclocarban, triclosan, and methyl

- triclosan in a North Texas, USA, stream affected by wastewater treatment plant runoff. Environ. Toxicol. Chem. 27(8): 1788

- 1793.

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Page 107 of 130 Coogan, M.A., R.E. Edziyie, T.W. LaPoint and B.J. Venables. 2007. Algal bioacc umulation of triclocarban, triclosan, and methyl

- triclosan in a North Texas wastewater treatment plant receiving stream. Chemosphere 67: 1911

- 1918.

Cortez, F.S., C.D.S. Pereira, A.R. Santos, A. Cesar, R.B. Choueri, G. A. Martini and M.B.Bohrer

- Morel. 2012. Biological effects of environmentally relevant concentrations of the pharmaceutical Triclosan in the marine mussel Perna perna (Linnaeus, 1758). Environ. Pollut. 168: 145

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Cuderman, P. and E. Heath. 2007. Determination of UV filters and antimicrobial agents in environmental water samples. Anal. Bioanal. Chem. 387(4): 1343

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DeLorenzo, M. E. and J. Fleming. 2008. Individual and mixture effects of selected pharmaceuticals and personal care products on the marine phytoplankton species Dunaliella tert iolecta . Arch. Environ. Contam. Toxicol. 54(2): 203

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DeLorenzo, M. E., J.M. Keller, C.D. Arthur, M.C. Finnegan, H.E. Harper, V.L. Winder and D.L. Zdankiewicz. 2008. Toxicity of the antimicrobial compound triclosan and formation of the metabolite meth yl

- triclosan in estuarine systems. Environ. Toxicol. 23(2): 224

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Duran

- Alvarez, J.C., B. Prado

- Pano, and B. Jiminez

- Cisneros. 2012. Sorption and Desorption of Carbamazepine, Naproxen, and Triclosan in a Soil Irrigated with Raw Wastewater: Estimation of the Sorption Parameters by Considering the Initial Mass of the Compounds in the Soil. Chemosphere 88 (2012) 84

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Dussault, E.B., V.K. Balakrishnan, E. Sverko, K.R. Solomon and P.K. Sibley. 2008. Toxicity of human pharmaceuticals and personal care products to benthic invertebrates. Environ. Toxicol. Chem. 27(2): 425

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European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC). 2007. Intelligent testing strategies in ecotoxicology: Mode of action approach for specifically acting chemi cals. Technical Report 102.

Fair, P. A., H.B. Lee, J. Adams, C. Darling, G. Pacepavicius, M. Alaee, G.D. Bossart, N. Henry and D. Muir. 2009. Occurrence of triclosan in plasma of wild Atlantic bottlenose dolphins ( Tursiops truncatus ) and in their environme nt. Environ. Pollut. 157(8

- 9): 2248

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Fang, J

- L., R.L. Stingley, F.A. Beland, W. Harrouk, D.L. Lumpkins, and P. Howard. 2010. Occurrence, Efficacy, Metabolism, and Toxicity of Triclosan. Journal of Environmental Science and Health, Part C: Environm ental Carcinogenesis and Ecotoxicology Reviews 28(3):147

- 171. DOI: 10.1080/10590501.2010.504978. http://www.tandfonline.com/doi/pdf/10.1080/10590501.2010.504978

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Page 108 of 130 Faust, M., R. A ltenburger, T. Backhaus, H. Blanck, W. Boedeker, P. Gramatica, V. Hamer, M. Scholze, M. Vighi and L.H. Grimme. 2001. Predicting the joint toxicity of multi

component s

- triazine muxtures at low

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Federle, T.W., S.K. Kaiser and B.A. Nuck. 2002. Fate and effects of triclosan in activated sludge. Environ. Toxicol. Chem. 21(7): 1330

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Ferarri, B., N. Paxeus, G. Pinto, A. Pollio, R. Andreozzi, R. Marotta, D. Vogna, G. Lyberatos and J. Garric. 2002. Fate and effect of triclosan in the aquatic ecosystems: Data for a risk assessment [poster]. In: Society of Environmental Toxicology and Che mistry Annual Meeting in Europe; 2002May 12

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Flaherty C.M. and S.I. Dodson. 2005. Effects of pharmaceuticals on Daphnia survival, growth, and reproduction. Chemosphere. 61: 200

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Focazio, M .J., D.W. Kolpin, K.K. Barnes, E.T. Furlong, M.T. Meyer, S.D. Zaugg, L.B. Barber and M. E. Thurman. 2008. A national reconnaissance for pharmaceuticals and other organic wastewater contaminants in the United States

— II) Untreated drinking water sources. Sci . Total. Environ. 402: 201

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non

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- mediated metamorphosis in Xenopus laevis

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- Based Acetochlor Class 2 Water Quality Standards for Minnesota. Compliance Services International.

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Page 109 of 130 Glassmeyer, S.T., E.T. Furlong, D.W. Kolpin, J.D. Cahill, S.D. Zaugg, S.L. Werne r, M.T. Meyer and D.D. Kryak. 2005. Transport of chemical and microbial compounds from known wastewater discharges: Potential for use as indicators of human fecal contamination. Environ. Sci. Tech. 39(14): 5157

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Halden, R.U. and D.H. Paull. 2005. Co

- occurrence of triclocarban and triclosan in U.S. water resources. Environ. Sci. Tech. 39(6): 1420

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Harada, A., K. Komori, N. Nakada, K. Kitamura and Y. Suzuki. 2008. Biological effects of PPC Ps on aquatic lives and evaluation of river waters affected by different wastewater treatment levels. Wat. Sci. Tech. 58(8): 1541

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Heidler J. and R.U. Halden. 2007. Mass balance assessment of triclosan removal during conventional sewage treatment. Che mosphere. 66: 362

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Heilman, K.E. 2008. Sublethal effects of triclosan on Potamogeton perfoliatus and Elodea canadensis . M.S. Thesis, Hood College, Frederick, MD. 57 p.

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Ishibashi, H., N. Matsumura, M. Hirano, M. Matsuoka, H. Shiratsuchi, Y. Ishibashi, Y. Takao and K. Arizono. 2004. Effects o f triclosan on the early life stages and reproduction of medaka Oryzias latipes and induction of hepatic vitellogenin. Aquat. Toxicol. 67: 167

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Kasprzyk

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Kim, J.W., H. Ishibashi, R. Yamauchi, N. Ichikawa, Y. Takao, M. Hirano, M. Koga and K. Arizono. 2009. Acute t oxicity of pharmaceutical and personal care products on freshwater

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Page 110 of 130 crustacean ( Thamnocephalus platyurus ) and fish ( Oryzias latipes ). J. Toxicol. Sci. 34(2): 227

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Kline, 200 5 . Specialty Biocides North America 200

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Kobayashi, N., S. Masunaga and J. Nakanishi. 2003. Source identification and behavior of PCDD/Fs and dioxin

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Kolpin, D.W., E.T. Furlong, M.T. Meyer, E. M. Thurman, S.D. Zaugg, L.B. Barber and H.T. Buxton. 2002. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999

- 2000: A national reconnaissance. Environ. Sci. Tech. 36(6): 1202

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Kolpin, D.W., M. Skopec, M.T. Meyer , E.T. Furlong and S.D. Zaugg. 2004. Urban contribution of pharmaceuticals and other organic wastewater contaminants to streams during differing flow conditions. Sci. Total Environ. 328(1

- 3): 119

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Küster A., K. Pohl and R. Altenburger. 2007. A fluoresc ence

- based bioassay for aquatic macrophytes and its suitability for effect analysis on non

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Latch, D.E., J.L. Packer, B.L. Stender, J. VanOverbeke, W.A. Arnold and K. McNeill. 2005. Aqueou s photochemistry of triclosan: formation of 2,4

- dichlorophenol, 2,8

- dichlorodibenzo

- p

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Lawrence, J.R., B. Zhu, G.D. Swerhone, J. Roy, L.I. Wassenaar, E. Topp and D.R. Korber. 2009

. Comparative microscale analysis of the effects of triclosan and triclocarban on the structure and function of river biofilm communities. Sci. Total Environ. 407(10): 3307

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Lee, H.B., K. Sarafin, T.E. Peart, and M.L. Svoboda. 2003. Acidic Pharmaceut icals in Sewage

— Methodology, Stability Test, Occurrence, and Removal from Ontario Samples. Water Qual. Res. J., Canada (38(4): 667

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Lee, C.J. and T.J. Rasmussen. 2006. Occurrence of organic wastewater compounds in effluent

dominated streams in Northea stern Kansas. Sci. Total Environ. 371(1

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Leiker, T.J., S.R. Abney, S.L. Goodbred and M.R. Rosen. 2009. Identification of methyl triclosan and halogenated analogues in male common carp ( Cyprinus carpio ) from Las Vegas Bay and semipermeable membr ane devices from Las Vegas Wash, Nevada. Sci. Total Environ. 407(6): 2102

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Lindstrom, A., I.J. Buerge, T. Poiger, P.

- A. Bergqvist, M.D. Muller and H.

- R. Buser. 2002.

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Page 111 of 130 Occurrence and environmental behavior of the bactericide triclosan and its methyl deri vative in surface waters and in wastewater. Environ. Sci. Tech. 36(11): 2322

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Page 119 of 130 

# APPENDIX E : Web

- ICE and ECOSAR Results

Saltwater Fish and Shrimp Predicted Values

The utility of ECOSAR v1.11 for predicting triclosan effect endpoints for saltwater fish and shrimp was checked by ex amining its success at predicting values for fresh water fish and the waterflea as compared to actual freshwater fish and daphnid data. In both cases ECOSAR values were less toxic than actual data (ECOSAR 96

- h LC 50 

### for fish = 476 ppb versus 260 ppb for fa thead minnow; ECOSAR 48

- hr EC 50 

### for daphnid = 469 ppb versus 390 ppb (which is an underestimate of toxicity) for actual Daphnia magna data), so in this case the ECOSAR model appears to underestimate triclosan toxicity to aquatic organisms. Therefore predi ctions using Web

- ICE v3.1 were examined as an alternative.

The most sensitive fish species was the fathead minnow (MRID 430460

- 01) 

### . The second most sensitive fish species was the rainbow trout ( MRID 439693

- 01 

### ). The utility of the Web

- ICE model using ra inbow trout for triclosan was checked by predicting the fathead minnow value using the rainbow trout. This species model resulted in a fathead minnow value ((95% lower confidence limit, mean) 514.8, 714.8) which underestimates toxicity (actual value (260 ppb)). Use of the fathead minnow as the surrogate species resulted in ecotoxicity values for other fish species that did not underestimate toxicity, therefore the fathead minnow value was used to predict a value for saltwater fish.

There are only four c hemical data points that Ceriodaphnia dubia (the more sensitive freshwater crustacean species) and Americamysis bahia have in common which means there is a high degree of uncertainty in estimates made using C. dubia . For the model predicting A. bahia from D.

magna there is 135 data points. Therefore the model using D. magna to predict A. bahia triclosan toxicity was used.

The ECOSAR and WEB

- ICE runs are provided at the end of this appendix:

ECOSAR Version 1.11 Results Page

SMILES : O(c(c(O)cc(c1)CL)c1)c (c(cc(c2)CL)CL)c2 CHEM : Phenol, 5

- chloro

- 2

- (2,4

- dichlorophenoxy)

- CAS Num: 003380

- 34

- 5 ChemID1: MOL FOR: C12 H7 CL3 O2 MOL WT : 289.55 Log Kow: 4.663 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: 4.76 (PhysProp DB exp value

- for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: 54.00 (deg C, PhysProp DB exp value for Wat Sol est, 54

- 57.3)

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Page 120 of 130 Wat Sol: 23.45 (mg/L, EPISuite WSKowwin v1.43 Estimate) Wat Sol: (User Entered) Wat Sol: 10 (mg/L, PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: 4.663 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 10 (mg/L, PhysProp DB exp value)

------------------------------------------------ Available Measured Data from ECOSAR Training Set

------------------------------------------------

No Data Available

-------------------------------------- ECOSAR v1.1 C lass

- specific Estimations

-------------------------------------- Phenols Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

========================== = ================== ======== ====== ========== Phenols : Fish 96

- hr LC50 0.476 Phenols : Daphnid 48

- hr LC50 0.469 Phenols : Green Algae 96

- hr EC50 1.665 Phenols : Fish ChV 0.071 Phenols : Daphnid ChV 0.089 Phenols : Green Algae ChV 0.756 Phenols : Fish (SW) 96

- hr LC50 0.131 Phenols : Earthworm 14

- day LC50 21.919 * Phenols : Lemna gibba 7

- day EC50 0.175

================ =========== ================== ======== ====== ========== Neutral Organic SAR : Fish 96

- hr LC50 0.965 (Baseline Toxicity) : Daphnid 48

- hr LC50 0.701 : Green Alga e 96

- hr EC50 1.443 : Fish ChV 0.126 : Daphnid ChV 0.136 : Green Algae ChV 0.653

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

------------------------------ Class Specific LogKow Cut

- Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut

- offs presented below, then no effects at saturation are expected for those endpoints.

Ph enols:

------- Maximum LogKow: 7.0 (Fish 96

- hr LC50, Daphnid LC50) Maximum LogKow: 6.4 (Earthworm, Lemna) Maximum LogKow: 7.0 (Green Algae EC50 Maximum LogKow: 8.0 (ChV) Maximum LogKow: 5.0 (Fish (SW) 96

- hr LC50, Mysid)

Baseline Toxicity SAR Limitations:

---------------------------------

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Page 121 of 130 Maximum LogKow: 5.0 (Fish 96

- hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)



### Web

- ICE

Surrogate Species Predicted Species Predicted Values Actual Value

Acute 95% C.L. df, R 2
Rainbow trout (288 ppb at pH 6.8

- 8.1 ) Fathead minnow 71 5 51 5, 992 79, 0.888 260 at pH 7.5

Fathead minnow (260 ppb at pH 7.5 ) Rainbow trout 141 97 , 206 79, 0.826 288 at pH 6.8

- 8.1

Fathead minnow (260 ppb at pH 7.5 ) Bluegill sunfish 188 121 , 293 66, 0.933 370 at pH

Ceriodaphnia dubia (235 ppb at pH 8.0

- 8.2 ) Daphnia magna 143 17 , 1196 6, 0.897 390 at pH 7.9

- 8.5

df = degrees of freedom ; R 2 = r

- squared or coefficient of determination

Surrogate Species Predicted Species Predicted Values Acute 95% C.L. df, R 2
Fathead minnow (260 ppb at pH 7.5) Sheepshead minnow 716 257, 1997 12, 0.537
Ceriodaphnia dubia (235 ppb at pH 8.0

- 8.2) Mysidopsis bahia 1 1 52 107, 216 135 , 0. 689

1 Name in model is former name, current nomenclature is Americamysis bahia



### Calculator

- Aquatic Species Surrogate Species: Rainbow trout ( Oncorhynchus mykiss ) Predicted Species: Fathead minnow ( Pimephales promelas )

Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

288 μg/L (2.45) 714.82 μg/L (2.85)

Select Confidence Interval: Lower Limit Upper Limit

95% 514.86 μg/L 992.45 μg/L
Model Information Intercept: 0.669768 Slope: 0.888200 Degrees of Freedom (N

- 2): 79 R 2 : 0.825954
p

- value: 0.000000

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Page 122 of 130 Average value of surrogate (log value): 1077.24 (3.03) Minimum value of surrogate (log value): 0.671479 (

- 0.172967) Maximum value of surrogate (log value): 9799999.99 (6.99) Mean Square Error (MSE): 0.372276 Sum of Squares (S xx ): 176.91 Cross

- validation Success (%): 82.71 Taxonomic Distance: 4

Surrogate Species: Fathead minnow (Pimephales promelas) Predicted Species: Rainbow trout (Oncorhynchus mykiss)

Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

260 μg/L (2.41) 141.46 μg/L (2.15)

Select Confidence Interval: Lower Limit Upper Limit

95% 97.28 μg/L 205.72 μg/L
Model Information Intercept:

- 0.095072 Slope: 0.929919 Degrees of Freedom (N

- 2): 79 R 2 : 0.825954
p

- value: 0.000000 Average value of surrogate (log value): 2307.11 (3.36) Minimum value of surrogate (log value): 1.18 (0.075366)

### Docket Number: EPA

- HQ

- OPP

- 2012

- 0811

Page 123 of 130 Maximum value of surrogate (log value): 10599999.99 (7.02) Mean Square Error (MSE): 0.389762 Sum of Squares (S xx ): 168.97 Cross

- validation Success (%): 87.65 Taxonomic Distance: 4

Surrogate Species: Fathead minnow (Pimephales promelas) Predicted Species: Bluegill (Lepomis macrochirus) Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

260 μg/L (2.41) 188.76 μg/L (2.27)

Select Confidence Interval: Lower Limit Upper Limit

95% 121.54 μg/L 293.17 μg/L

Model Information Intercept: 0.022235 Slope: 0.933218 Degrees of Freedom (N

- 2): 66 R 2 : 0.790938
p

- value: 0.000000 Average value of surrogate (log value): 1843.51 (3.26) Minimum value of surrogate (log value): 1.18 (0.075366) Maximum value of surrogate (log value): 10600000.00 (7.02) Mean Square Error (MSE): 0.475436 Sum of Squares (S xx ): 136.31 Cross

- validation Success (%): 80.88 Taxonomic Distance: 4

### Docket Number: EPA

- HQ

- OPP

- 2012

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Page 124 of 130 Calculator

- Aquatic Species Surrogate Species: Fathead minnow ( Pimephales promelas ) Predicted Species: Sheepshead minnow ( Cyprinodon variegatus ) Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

260 μg/L (2.41) 715.97 μg/L (2.85)

Select Confidence Interval: Lower Limit Upper Limit

95% 256.71 μg/L 1996.82 μg/L

Model Information Intercept: 1.62 Slope: 0.507579 Degrees of Freedom (N

- 2): 12 R 2 : 0.536675
p

- value: 0.002883 Average value of surrogate (log value): 2230.26 (3.34) Minimum value of surrogate (log value): 2.68 (0.428134) Maximum value of surrogate (log value): 186000.00 (5.26) Mean Square Error (MSE): 0.358983 Sum of Squares (S xx ): 19.36 Cross

- validation Success (%): 78.57 Taxonomic Distance: 4

### Docket Number: EPA

- HQ

- OPP

- 2012

- 0811

Page 125 of 130 Surrogate Species: Daphnid (Ceriodaphnia dubia) Predicted Species: Daphnid (Daphnia magna) Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

235 μg/L (2.37) 143.17 μg/L (2.15)

Select Confidence Interval: Lower Limit Upper Limit

95% 17.13 μg/L 1196.11 μg/L
Model Information Intercept: 0.309565 Slope: 0.778676 Degrees of Freedom (N

- 2): 6 R 2 : 0.804347
p

- value: 0.002535 Average value of surrogate (log value): 911.76 (2.95) Minimum value of surrogate (log value): 0.150395 (

- 0.822764) Maximum value of surrogate (log value): 8808000.00 (6.94) Mean Square Error (MSE): 1.06 Sum of Squares (S xx ): 43.42 Cross

- validation Success (%): 37.5 Taxonomic Distance: 2

### Docket Number: EPA

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- OPP

- 2012

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Page 126 of 130 Surrogate Species: Daphnid ( Ceriodaphnia dubia ) Predicted Species: Mysid ( Americamysis bahia ) Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

235 μg/L (2.37) 172.48 μg/L (2.23)

Select Confidence Interval: Lower Limit Upper Limit

95% 3.70 μg/L 8031.21 μg/L
Model Information Intercept: 0.090613 Slope: 0.905133 Degrees of Freedom (N

- 2): 2 R 2 : 0.964719
p

- value: 0.017798 Average value of surrogate (log value): 905.88 (2.95) Minimum value of surrogate (log value): 0.050000 (

- 1.30) Maximum value of surrogate (log value): 8097999.99 (6.90) Mean Square Error (MSE): 0.580494 Sum of Squares (S xx ): 38.74 Cross

- validation Success (%): 0.00 Taxonomic Distance: 5

### Docket Number: EPA

- HQ

- OPP

- 2012

- 0811

Page 127 of 130 Surrogate Species: Daphnid ( Daphnia magna ) Predicted Species: Mysid ( Americamysis bahia ) Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

260 μg/L (2. 59 ) 152.19 μg/L (2. 18 )
Select Confidence Interval: Lower Limit Upper Limit

95% 107.28 μg/L 215.89 μg/L
Model Information Intercept: 0.087748 Slope: 0.808413 Degrees of Freedom (N

- 2): 135 R 2 : 0.688969
p

- value: 0.000000 Average value of surrogate (log value): 375.54 (2.57) Minimum value of surrogate (log value): 0.070000 (

- 1.15) Maximum value of surrogate (log value): 839999.99 (5.92) Mean Square Error (MSE): 0.822216 Sum of Squares (S xx ): 376.22 Cross

- validation Success (%): 64.96 Taxonomic Distance: 5

### Docket Number: EPA

- HQ

- OPP

- 2012

- 0811

Page 128 of 130

### Docket Number: EPA

- HQ

- OPP

- 2012

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Page 129 of 130 

# APPENDIX F : For Ecological Assessment

Dioxins of Concern and Equivalency Factors

The term “dioxins” is used to represent polychlorinated dibenzo

- p

- dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). There are 210 different congeners of dioxins (75 PCDDs and 135 PCDFs); however, only 17 congeners are considered to be of toxicological concern (listed in Table 34 ). For t hese 17 congeners, evidence is sufficient to conclude that a common mechanism of action, involving binding of the chemicals to the aryl hydrocarbon receptor (AHR) as the initial step, underlies 2,3,7,8

- TCDD

- like toxicity elicited by these PCDDs, PCDFs, and Polychlorinated biphenyls (PCBs) (Van den Berg et al ., 1998, 2006; Hahn, 2002).

Another possible source of toxicity from the use of triclosan is the presence of dioxins from interaction with chlorinated water. Dioxin congeners that form from triclosan ar e 2,7

- dibenzodichloro

- p

- dioxin

, 2,8

- dichloro

- p

- dioxin

, 1,2,8

- and 2,3,7

- trichlorodioxins and 1,2,3,8

- tetrachlorodioxin in natural waters

. These congeners are not among the 17 (listed below) that are of toxicological concern for mammals, birds, and fish.

Table 35

- Dioxin Congeners of Toxicological Concern; Toxicity equivalency factors for mammals, birds and fish associated with each isomer are from U.S. EPA 2008b Congener* Mammal TEF Bird TEF Fish TEF
2378

- TCDF 0.1 1 0.05 12378

- PeCDF 0.03 0.1 0.05 23478

- PeCDF 0.3 1 0.5 123478

- HxCDF 0.1 0.1 0.1 123678

- HxCDF 0.1 0.1 0.1 234678

- HxCDF 0.1 0.1 0.1 123789

- HxCDF 0.1 0.1 0.1 1234678

- HpCDF 0.01 0.01 0.01 1234789

- HpCDF 0.01 0.01 0.01 OCDF 0.0003 0.0001 <0.0001 2378

- TCDD 1 1 1 12378

- PeCDD 1 1 1 123478

- HxCDD 0.1 0.05 0.5 123678

- HxCDD 0.1 0.01 0.01 123789

- HxCDD 0.1 0.1 0.01 1234678

- HpCDD 0.01 <0.001 0.001 OCDD 0.0003 0.001 <0.001 *Abbreviations are as follows: TCDD = tetrachlorodibenzodioxin; PeCDD = pentachlorodibenzodioxin; HxCDD = hexachlorodibenzodioxin; HpCDD = Heptachlorodibenzodioxin; OCDD = Octachlorodibenzodioxin; TCDF =

### Docket Number: EPA

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Page 130 of 130 Tetrachlorodibenzofuran; PeCDF = Pentachlorodibenzof uran; HxCDF = Hexachlorodibenzofuran; HpCDF = Heptachlorodibenzofuran; OCDF = octachlorodibenzofuran


### Research has been conducted to characterize the toxicities of PCDDs and PCDFs especially relative to each other, since these compounds are often present to gether in the environment. Demonstrated toxic effects of 2,3,7,8

- TCDD and other similar

- acting PCDD, PCDF and PCB congeners in fish, birds, and mammals include adverse effects on reproduction, development, and endocrine functions; wasting syndrome; immunot oxicity; and mortality in both laboratory and field settings (U.S. EPA 2008b). The EPA (U.S. EPA 2008b) and the World Health Organization (Van Den Berg et al. 1998 and 2006) have established toxicity equivalency factors (TEFs) for dioxins as they relate t o mammals, to birds and to fish ( Table 34 ). In the TEF approach, the toxicities of individual congeners are related to 2,3,7,8

- TCDD, which is the most toxic congener of dioxins to animals For each PCDD and PCDF, the concentration (or mass) of the chemical is multiplied by its TEF. The sum of the product for each PCDD and PCDF represents the toxicity equivalent (TEQ) concentration relative to 2,3,7,8

- TCDD (Equation 1; U.S. EPA 2008b).

Equation 1

. 

# ∑
=

n n n 

### TEF ion Concentrat TEQ *



### Dioxins, and HCB are both listed under the Stockholm Convention as Persistent Organic Pollutants (POPs). These chemicals are persistent, bioaccumulative and subject to long range transport. In general, chronic toxicity endpoints for mammals and birds exposed to pesticides are expressed in terms of mg pesticide/kg

- bw. The toxicity of 2,3,7,8

- TCDD is expressed in units of ng/kg

- bw, which indicates that this chemical is orders of magnitude more toxic than pesticides which are typically assessed by OPP. When using t he TEQ approach, the exposure concentration of each dioxin congener is adjusted relative to the toxicity of 2,3,7,8

- TCDD. Based on the dioxin congeners formed from triclosan, calculation of total TEQ is not required, as the congeners formed are not of tox icological concern.