### Docket Number: EPA-HQ-OPP-2012-0811

Page 2 of 116 Triclosan Registration Review Team

Human Health William Hazel 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 Lance Wormell

Office of General Counsel Philip Ross Andrea Medici

### Docket Number: EPA-HQ-OPP-2012-0811

Page 3 of 116 

## Table of Contents

1 Introduction .................................................................................................................. ........... 6

1.1 Statutory and Regulatory Authority ................................................................................. 6

1.2 Case Overview ................................................................................................................. 8

1.3 Chemical Identification and Properties ............................................................................ 8

1.4 Use/Usage Description ................................................................................................... 10

1.4.1 Summary of Regist ered Uses .................................................................................. 10

1.4.2 Usage Information .................................................................................................. 12

1.5 Regulatory History ......................................................................................................... 13

1.5.1 Recent/Pending Regulatory Actions ....................................................................... 14

1.5.2 Tolerance Information ............................................................................................ 16

1.6 Incidents ..................................................................................................................... .... 17

1.6.1 Human Health ......................................................................................................... 17

1.6.2 Ecological ............................................................................................................... 17

2 Anticipated Data Needs ........................................................................................................ 17

3 Human Health Risk Assessment ........................................................................................... 21

3.1 Existing Toxicological Endpoints .................................................................................. 21

3.2 Dietary Exposure ............................................................................................................ 2 2

3.3 Occupational and Residential Exposures ....................................................................... 23

3.3.1 Occupational Handler Exposures ............................................................................ 23

3.3.2 Residential Handler Exposures ............................................................................... 23

3.3.3 Residential Post-Applic ation Exposures ................................................................. 23

3.4 Aggregate and Cumulative Exposure ............................................................................. 24

3.4.1 Aggregate Exposures .............................................................................................. 24

3.4.2 Cumulative Exposures ............................................................................................ 25

4 Environmental Risk Assessment........................................................................................... 25

4.1 Environmental Conceptual M odel Exposure Pathways ................................................. 26

4.2 Ecological Effects Assessment ....................................................................................... 28

4.2.1 Mechanism of Action .............................................................................................. 28

### Docket Number: EPA-HQ-OPP-2012-0811

Page 4 of 116 4.2.2 Measures of Effect (Ecotoxicology Endpoints) ...................................................... 29

4.3 Exposure Analysis Plan .................................................................................................. 31

4.3.1 Aquatic and Terrestrial Wild life Exposure Estimates ............................................ 31

4.3.2 Textile Manufacturing Monitoring Data ................................................................. 31

4.4 Effects Analysis Plan ..................................................................................................... 33

5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 34

6 Guidance for Commenters .................................................................................................... 35

6.1 Preliminary Work Plan ................................................................................................... 35

6.1.1 Trade Irritants .......................................................................................................... 35

6.1.2 Water Quality .......................................................................................................... 35

6.1.3 Environmental Justice ............................................................................................. 36

6.1.4 Structure Activity Relationships ............................................................................. 36

6.1.5 Additional Information ........................................................................................... 37

7 Next Steps .................................................................................................................... ......... 37

8 References .................................................................................................................... ......... 38 APPENDIX A: Toxicology Profile .............................................................................................. 3 9

APPENDIX B: Environmental Fate ............................................................................................. 54 APPENDIX C: Ecotoxicology Profile .......................................................................................... 72

APPENDIX D: Web-ICE and ECOSAR Results ....................................................................... 107 APPENDIX E: For Ecological Assessment- Dioxi ns of Concern and Equivalency Factors ..... 115

List of Tables

Table 1 - Summary of Anticipated Ri sk Assessments and Data Needs ......................................... 7 Table 2 - Anticipated Registration Review Schedule ..................................................................... 7 Table 3 - Chemical Identification of Triclosan ............................................................................... 8 Table 4 - Physical-Chemical Properties for Triclosan .................................................................... 9 Table 5 - Triclosan Antimicrobial Use Summary ......................................................................... 10 Table 6 – Studies Anticipated as Needed for Registration Review of Triclosan .......................... 18 Table 7 –Data Needs Required by the Da ta Call-In for the Triclosan RED ................................ 19 Table 8 - Toxicological Endpoints Used for the Triclosan RED .................................................. 21 Table 9 - Occupational Handler Expo sure Scenarios for Triclosan ............................................. 23 Table 10 - Effects Endpoints for the Ecologi cal Risk Assessment of Triclosan .......................... 29 Table 11—Textile Facility Characteristics Du ring the Triclosan Monitoring Studies ................. 32

### Docket Number: EPA-HQ-OPP-2012-0811

Page 5 of 116 Table 12—Triclosan and Methyl Triclosan Moni toring Data from Two Textile Manufacturing Facilities .................................................................................................................... .................... 33 Table 13 - Acute Toxicity Profile for Triclosan ........................................................................... 39 Table 14 - Non-Acute Toxicity Studies for Triclosan .................................................................. 40 Table 15 - Abiotic Degradation of Tr iclosan and Degradate Formation ...................................... 57 Table 16 - Metabolism of Triclosan w ith Formation of Degradates ............................................ 60 Table 17 - Effect of pH on the Ionization of Triclosan at 20 o 

### C ................................................... 62 Table 18 - Leaching and Adsorption-Desorption of Triclosan to Soil and Sediment .................. 62 Table 19 - Terrestrial Field Dissipation, Surf ace Runoff, Leaching, and Crop Uptake ............... 63 Table 20 - Environmental Monitori ng Studies for Triclosan ........................................................ 66 Table 21 – Biological Field Monito ring of Aquatic Organisms ................................................... 69 Table 22 - Textile Monitoring Facility Characteristics ................................................................. 71 Table 23 - Textile Triclosan and Methyl Tr iclosan Monitoring Concentrations .......................... 71 Table 24 - Toxicity of Triclosan to Birds ..................................................................................... 72 Table 25 - Acute Toxicity of Triclosan to Aquatic Animals from Submitted Studies and Reviewed Open Literature ...................................................................................................... ...... 77 Table 26 - Acute Toxicity of Triclosan to Aqua tic Animals from Open Literature Provided by OW ............................................................................................................................ .................... 80 Table 27 - Chronic Toxicity of Triclosan to Aquatic Animals from Submitted Studies and Reviewed Open Literature ...................................................................................................... ...... 82 Table 28 - Chronic Toxicity of Triclosan to A quatic Animals from Open Literature Provided by OW ............................................................................................................................ .................... 84 Table 29 - Toxicity of Triclosan to Sediment Benthos from Submitted Studies .......................... 85 Table 30 - Toxicity of Triclosan to Aquatic Plants from Submitted Studies ................................ 86 Table 31 - Toxicity of Triclosan to Aquatic Plan ts from Open Literature Reviewed by OW ...... 87 Table 32 - Other Chronic Data on the Effects of Triclosan on Aquatic Organisms from Open Literature Reviewed by OW ..................................................................................................... .... 88 Table 33 - Acute Toxicity of Me thyl Triclosan to Aquatic Organisms from Open Literature Provided by OW ................................................................................................................ ........... 93 Table 34 - Dioxin Congeners of Toxicological Concern; Toxicity equivalency factors for mammals, birds and fish associated with each isomer are from U.S. EPA 2008b ..................... 115

List of Figures

Figure 1 - Conceptual Model for Environmenta l Exposure from Treatment of Textiles with Triclosan ..................................................................................................................... .................. 27 Figure 2 - Conceptual Model for Environmental Exposure from In-Service Use of Triclosan in Plastic Agricultural Film and Mulch ........................................................................................... .. 28

### Docket Number: EPA-HQ-OPP-2012-0811

Page 6 of 116 

## 1 Introduction

This document is the Environmen tal Protection Agency’s (EPA or “the Agency”) Preliminary Work Plan (PWP) for triclosan. The PWP documen t explains what EPA's Office of Pesticide Programs knows about triclosan, highlighting antic ipated data and assessment needs, identifying the types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timelin e for completing triclosan’s review.

The registration review process was designed to include a publi c participation component to solicit input from interested stak eholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about triclosan and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on triclosan. The Agency encourages all interested stakeholders to review the PWP and to provide comments and additional information that will he lp the Agency’s decision-making process for this chemical.



### 1.1 Statutory and Regulatory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the U.S. Environmental Protection Agency (USEPA, EPA, or the Agency ) based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The regist ration 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 th e statutory standard of no unreas onable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency pe riodically reevaluates pesticides to make sure that as change occurs , products in the marketpl ace can be used safely. Information on this program is provided at http://www.epa.gov/oppsrrd 1/registration_review/.

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing regi stration review begin at 40 CFR 155.40. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registrati on review decision. After reviewing and responding to comments and data received in the docke t during this initial comment period, the Agency will develop and commit to a final work plan and schedule for the Triclosan Case (PC Code 054901) (Case Number 2340). Documents associated with this registration review can be viewed at www.regulations.gov in docket EPA-HQ-OPP-2012-0811. Below is a summary of the issues releva nt to this registra tion review case.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 7 of 116 Table 1 - Summary of Anticipated Risk Assessments and Data Needs

Risk Assessment Assessment 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 PostApplication – Incidental Oral and Dermal Yes 1 2008 Updated None

Residential PostApplication – 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 and mollusk; daphnid, mysid and fish life cycle tests; Post-RED ecotox data; leaching from agricultural film and mulch 2

1 Dietary (food and drinking water) and reside ntial exposure are part of the general popul ation biological monitoring data from NHANES and will be accounted for in th e anticipated aggr egate assessment.

2 EPA has received a request to terminate the use of triclosan in agricultural films and mulches. If the cancellation order becom es 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: Openin g the Docket Open Docket and 60-Day Public Comment Period for Preliminary Work Plan 2013-03 2013-03-27

Close Public Comment Period 2013-05 Phase 2: Case Development
Issue Final Work Plan 2014-09 Issue Data Call-In (DCI) 2015-09
Receive Data to be Considered in Risk Assessment 2017-09 Open 30-Day Public Comment Period for Proposed Decision 2019-03
Close Public Comment Period 2019-04 Phase 3: Registration Review Decision and Implementation

### Docket Number: EPA-HQ-OPP-2012-0811

Page 8 of 116 Open 60-Day Public Comment Period for Proposed Decision 2020-09
Close Public Comment Period 2020-11
Issue Final Decision 2020-03 Begin Post-Decision Follow-up 2020 Total (years) 7

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



### 1.2 Case Overview The triclosan case (case #2340) contains one ch emical, 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 fi rst registered by the United States on June 19, 1969 as a bacteriostat. Presently, there are 9 registered products under PC Code 054901. There are no approved inert uses for triclosan. Triclosa n is registered for use as a bacteriostat and fungistat in plastics, po lymers, and textile products during th e manufacturing process to impart antibacterial properties. It is also registered for use on hard non-porous surfaces of heating, ventilation and air conditioning (HVAC) excha nge coils as a bacteriostat, fungistat and mildewstat. The Agency completed a Reregist ration Eligibility Decision (RED) Document for triclosan in September 2008.



### 1.3 Chemical Identification and Properties

The chemical identification information for triclosa n is listed in Table 3. Triclosan 5-Chloro-2- (2,4-dichlorophenoxy) phenol(PC Code 054901) is a substituted di phenyl ether compound containing chlorine atoms in the 2, 4, and 4’ position. It includes both phenol and ether functional groups.

Table 3 - Chemical Identi fication of Triclosan

Common Name Triclosan
Chemical Name 5-Chloro-2-(2,4-dichlorophenoxy) phenol Classification Diphenyl ether; Polychloro phenoxy phenol
PC Code 054901 CAS No. 3380-34-5 Molecular Formula C 12 H 7 Cl 3 O 2 Molecular Weight 289.541

### Docket Number: EPA-HQ-OPP-2012-0811

Page 9 of 116 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. Details 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 solubl e 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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 10 of 116 

### 1.4 Use/Usage Description The products containing triclosan as the activ e ingredient (ai) include ready-to-use, pelleted/tableted, emulsifiable concentrate, and soluble concentrate formulations and impregnated materials. Concentrations of tr iclosan in these products range widely from 0.69%

to ≥ 99%.

1.4.1 Summary of Registered Uses Table 5 presents a summary of the registered uses of triclosan. There ar e currently 6 registrants and a total of 9 registered products. Triclosa n is currently register ed under FIFRA as a bacteriostat, fungistat, and mildew stat for use as a material pres ervative of products used in residential, public access, commercial, institutional and industrial premises.

Except for the HVAC use product, triclosan is inco rporated into or coated onto materials at manufacturing facilities by liqui d 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 is not availa ble for use by home owners. There are no EPA registered products containing tric losan that can be applied dir ectly by the homeowner; however, articles treated with triclosan are used by cons umers and have the poten tial for post-application residential exposure. Triclosan- treated articles that may routin ely be used in the residential market include, but are not limited to, material preservative uses in mattresses, clothing, bibs, tooth brush bristles, plastic t oys, plastic cutting boards, ga rbage bags, paper, playground equipment, sponges, furniture, carpeting, rugs, floor ing, floor waxes and seal ers, and footwear.

Table 5 - Triclosan Antimicrobial Use Summary

Use Application Method (liquid pour, solid/powder pour ) Product Application Rate 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.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 11 of 116 Feathers & Down Incorporation 0.8-1.5 % Apparel: aprons, athletic shirts, bibs, dresses, footwear (including socks & Innersoles), 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 %

42182-1 Floor coverings: carpets, rugs, mats, sealer/wax components. Incorporation 0.1-1.00 % Home furnishings: blankets, cloths, countertops, curtains, draperies, furniture & fabric s, 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, br ushes, buckets, carts, closure gaskets, conveyer belts, countertops (& covers), earplugs, garbage cans, hosing (non food; non-potable water transfer), janitorial supplies, mops, respirator mask components, tabletops, trays, wipes. Incorporation 0.1-1.00 %

Ice making equipment (water pans, piping, tubing, guards) Incorporation 0.1-0.5 % 42182-1
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 % 42182-1

Textiles and Fabrics; Apparel trimmings and linings, Aprons (food service, home), Athletic Wear, Awnings (Indoor and outdoor), Bibs, Blanket bags, Blankets, Brushes, Carpets and Rugs, Conveyor belts, Covers for counter tops, Covers for table tops, Cubicle curtains, Door and floor mats, Dresses, Incorporation 0.1-2.00 % 86110-1

2 EPA has received a request to terminate the use of triclo san in agricultural films and mulches. If the cancellation order becomes effective and all product labels are ame nded to remove the use, this table will be updated accordingly.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 12 of 116 Exercise equipment, Floor co verings, Food Services wipes(towels), Furniture fabrics, Garment bags, Gloves (nonmedical), 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, Mops, Paper mulch, Pillow and mattress stuffing, Quilt fabric, Running apparel, Uniforms, Shoes, shoe inner soles and linings, Shower curtains, Silage wraps, Sporting team uniform s, Sportswear, Sweatshirts/tshirt, Table clothes, napkins, Tooth brush bristles, Uniforms, Wall Coverings, Wet Suits, Wi ndow 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, component, fibers, & coatings of urethane, epoxy etc. ), Floral containers, Food distribution carts, Food service trays, Furniture coverings, Furniture foam cushions, Garbag e bags and trash can liners, Garbage cans, Grease traps, Medical & dental trays, Menu materials, 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 handles, 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 handles, serving utensils, bed pans, and floor drains Incorporation 0.1-1.00%

Industrial Processes and Water Systems

HVAC coils Airless sprayer Not listed 82523-1



### 1.4.2 Usage Information According to the Kline Biocides Report fo r 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 es timated U.S. consumption of specialty biocides in plastics by volume and 6 per cent by value. The consumption in plastics was forecasted to grow at an annual rate of 1.5% through 2009.

The Kline Report also notes that: “The exceptional growth previously exp ected for triclosan over the last five years has not rea lized due to several factors, including the EPA’s ruling on public health claims. This “Treated Articles Exempti on” only allows for claims that biocides protect

### Docket Number: EPA-HQ-OPP-2012-0811

Page 13 of 116 the integrity of the plastic, and disallows antimic robial claims, for instance for an antimicrobial cutting board or countertop, unless that consumer product itself is registered with the EPA”



### 1.5 Regulatory History The most recent comprehensive risk assessmen t performed by OPP on triclosan was conducted in support of the 2008 Reregistra tion Eligibility Deci sion (RED). As part of the RED, OPP performed a comprehensive review of the hazards, exposures and risks to human health and the environment resulting from the registered pesticid al 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 Nutr ition Examination Survey (NHANES) biological monitoring data collected by the Center for Dis ease Control and Prevention (CDC). NHANES is a program designed to assess the he alth and nutritional st atus of adults and children in the United States by examining a nationally representati ve sample of about 5,000 persons each year (http://www.cdc.gov/nchs/nhanes/ about_nhanes.htm). The aggreg ate risk assessment took all post-application exposures to tr iclosan into account including bot h 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 Agency concluded that total exposure to triclosan from all sources did not presen t risks of concern for human health.

The agency conducted a qualitative environmenta l risk assessment as part of the RED using existing ecotoxicity studies, USGS monitored levels of tr iclosan found in waterways and consumer product environmental modeling. Th e Agency 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 Agency issued a post-RED Data Call-In (DCI) requiring monitoring data on the effluent of manufacturing f acilities using triclosan. These m onitoring data, along with effects data anticipated to be needed for the registrati on 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 triclosan as a material preservative in paint was found ineligible. The registrant requested vol untary cancellation; the paint uses for triclosan will be removed from product labels prior to risk assessment, see section 1.5.1.)

In response to the research on human health effects (US EPA / Office of Research and Development) that was ongoing at the time of the RED and public concern regarding triclosan, the Agency has decided to undertake another comprehensive review of triclosan under the Registration Review Program beginning in Fiscal Year 2013, ten years earlier than originally planned. Since 2008, OPP has engaged in several key e fforts that will ensure that our review of triclosan is timely, scientifically sound and transparent, with a ppropriate public participation.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 14 of 116 In the RED, the Agency acknowledg ed scientific literat ure suggesting potential endocrine effects of triclosan and committed to examining the endocrine interactions of triclosan further. Since 2008, the Office of Pesticide Programs has collaborat ed with the EPA’s Office of Research and Development (ORD) on the conduct of additional studi es to investigate the endocrine effects of triclosan. In particular, ORD investigated the effects on th e androgen, estrogen, and thyroid hormone systems using a variety of experimental approaches. The Agency presented some of this information as part of a case study duri ng the “Integrated Appro aches to Testing and Assessment strategies (IATA): Use of New Computational and Mol ecular Tools” FIFRA Scientific Advisory Panel (SAP ) consultation in May, 2011. The tr iclosan case study presented to the SAP was not a full risk assessment.

As background information for the case study presen ted at the SAP, the Agency also released an updated draft exposure assessment for triclosan that incorporat ed NHANES data that became available after the completion of the 2008 RE D. The draft exposure assessment included NHANES data for ’05-’06 and ’07-’08 in addition to the ’03-’04 data that the Agency utilized for the RED risk assessment. The Agency has no t developed any new conc lusions 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 NHANES data will be taken into account during the comprehensive human hea lth risk assessment that will be performed as part of the registration review of triclosan. Documents rela ted to the SAP can be found at regulations.gov in docket EPA-HQ-OPP-2011-0284.

1.5.1 Recent/Pending Regulatory Actions In March 2013 the Agency received a request to amend triclosan labels for EPA registration numbers 42182-1 and 42182-7 to terminate the us e in agricultural films and mulches. EPA intends to publish a notice in the Federal Register in the near future announcing th e receipt of the request pursuant to FIFRA section 6(f). In 2012 and 2013 the EPA published Cancellation Orders for EPA Registration Nu mbers 2829-139, 2829-145, 4822-429, 3090-165, 5383-127 and 10466-24 as a result of requests for voluntar y cancellation. EPA Registration Number 83884-7 was cancelled in 2012 due to non-payment.

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 Agency (EPA). The petition specifically requested that the Agency take the fo llowing steps under each of the following statutes:

FIFRA and FFDCA: (1) reopen th e Reregistration Eligibility Decision (RED) (2) issue a notice of cancellation of the registrations of all products containing triclosan and (3)

### Docket Number: EPA-HQ-OPP-2012-0811

Page 15 of 116 concurrently issue an emergency order to immediately suspend the existing triclosan registrations;

CWA: (1) impose technology-based effluent lim itations, (2) establish health-based toxic pollutant water quality pretreatment require ments 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 a nd (2) engage in consultation with the Secretary of the Interior a nd 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-HQ-OPP-2010-0548. Th e Agency’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 proce ss initiated with this PWP. However, the petitioners, along w ith the public in general, will have multiple opportunities to participate in the registration review when they can contribute to the discussion of any scientific issues in relation to data devel oped since the RED, as well as any data that are submitted as part of this registration review.

Assessments by Other Regulatory Agencies

In 2012, Health Canada and Environment Canada jointly published a prel iminary assessment of the human health effects and environmental toxicity of triclosan (available at: http://www.chemicalsubstanceschimiques.gc.ca/ plan/approach-approche /triclosan-eng.php). In Canada, triclosan is subject to regulation under the Pest Control Products Act (PCPA) (Canada 2002), the Food and Drugs Act (Canada 1985) and the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada 1999). In that preliminar y 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 text iles and food contact materials, such as cutting boards and countertops ), drinking water contaminated with triclosan, breast milk, and contaminated household dust. E xposure of the general p opulation to triclosan was characterized using the available biomonito ring 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 char acterize the exposure of children under the age of 6 years to triclosan. Environmental exposures were assessed using measured data for

### Docket Number: EPA-HQ-OPP-2012-0811

Page 16 of 116 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 th at constitute or may constitute a danger in Canada to human life or health. However, it was c oncluded that with respect to the environment, triclosan “is entering or may enter the environm ent in a quantity or concentration or under conditions that have or may have an immediate or long-term ha rmful effect on the environment or its biological diversity.” U nder the PCPA, Health Canada c oncluded that the use of pest control products 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 triclosa n treated products (e.g., tr eated plastics, textiles, leather, paper and rubber), pest control products are not expected to c ontribute significantly to the risks to aquatic organisms.

In 2009, the National Industrial Chemicals No tification and Assessment Scheme (NICNAS) within the Australia Government Department of Health and Ageing published a full risk assessment on the public health, occupational hea lth and safety, and environmental effects of industrial uses of triclosan (available at: http://www.nicnas.gov.au/Pub lications/CAR/PEC/PEC30/ PEC_30_overview_PDF.pdf). Triclosan is not manufactured in Australia but is imported for use in the formulation of personal care and cosmetic products; therapeu tic products; cleaning agents; in the treatment of textiles and in plastics manufacture; in the formulation of some oil-based paints; and in grouting material

. That assessment concluded that under normal c onditions of exposure for occupational workers and under normal conditions of use for residentia l populations, the risk of adverse effects from exposure to triclosan was low. It was acknowle dged that repeated us e of cosmetic products containing triclosan could lead to increased levels of exposure and thus to increased risk. With regard to environmental risk, it was conclude d that there was no evidence that the use of triclosan was leading to developm ent of triclosan-resi stant bacterial populati ons or any increased risk to humans regarding antibiotic resistance. The assessment identified that triclosan is highly toxic to a number of freshwater aquatic orga nisms, with freshwater algae being the most sensitive species. The major environmental 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 aqua tic plants are at worst ‘marginal,’ but that adverse effects on algae could result from current levels in the environment. The application of biosolids contai ning triclosan to fields was identi fied as an area of concern for which more study of the effect of triclosan on microbial soil populations was identified.

1.5.2 Tolerance Information There are no tolerances or tolerance exemptions for triclosan. The n eed for tolerances or tolerance exemptions will be revisited during registration review.

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### 1.6 Incidents

1.6.1 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 re ported incidents, only one incident is considered triclosan-specific. The incident was reported to th e Agency in January of 2011 and involved symptoms in an indivi dual who had hand washed a sma ll amount of clothing with an anti-bacterial hand soap contai ning 0.15% triclosan. The indivi dual reported symptoms including allergic reactions, headache, chemical taste in the mouth, complete loss of appetite, muscle twitches, and atrophy. The individua l also reported that he had de veloped a full blown chemical sensitivity to triclosan. These symptoms were re ported by the individual a nd no further details of the symptoms were provided, nor were these sy mptoms verified by a doctor or other health professional. The specific amount of triclosan to which the individual was exposed could not be determined from the description provided.

1.6.2 Ecological
No incidents involving triclosan we re reported in the following da tabases as of February 7, 2013: Ecological Incident Information System, versi on 2.1.1, the Aggregate Incident Data System, and the Avian Incident Monitoring System (AIMS) 3



### .



## 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 , the following studies as listed in Table 6 are expected to be needed for the registration revi ew of Triclosan. Ta ble 7 outlines the data requirements required by the post-RED DCI issu ed on October 5, 2011. The Agency anticipates reviewing any data received in response to the po st-RED DCI as well as data requested for this registration review prior to conducting the regist ration review risk assessments for triclosan.

3 http://www.abcbirds.org/abcprograms/policy/toxins/aims/aims/index.cfmDocket Number: EPA-HQ-OPP-2012-0811Page18of116Table 6 – Studies Anticipated as Neededfor Registration Review of TriclosanGLNStudy NameTest SubstanceTime Frame(Measured inmonths fromDCI Receipt)Risk Assessment(s)Data Will SupportUse Site(s) Triggering AnticipatedData RequirementApplicableExposure ScenarioSpecialStudy1,2Leaching from plasticagricultural mulchTGAI 24Environmental Fate,EcologicalPlastic/polymer agriculturalmulch/filmIn-service use850.10252,4or 850.1055Acute mollusk TGAI 12 EcologicalTextile application, plastic/polymeragricultural mulch/filmEffluent dischargeand in-service use,respectively850.10352,4Mysid acute TGAI 12 EcologicalTextile application, plastic/polymeragricultural mulch/filmEffluent dischargeand in-service use,respectively850.13002,4,5Daphnid Life CyclestudyTGAI 12 EcologicalTextile application, plastic/polymeragricultural mulch/filmEffluent dischargeand in-service use,respectively850.13502Mysid life cycle TGAI 12 EcologicalTextile application, plastic/polymeragricultural mulch/filmEffluent dischargeand in-service use,respectively850.15001,2,4,5Freshwater fish fulllife cycleTGAI 24 EcologicalTextile application, plastic/polymeragricultural mulch/filmEffluent dischargeand in-service use,respectively875.1200Indoor Exposure,DermalMP; EP 24 Occupational HVAC coils Airless sprayer875.1400Indoor Exposure,InhalationMP; EP 24 Occupational HVAC coils Airless sprayer1The anticipated DCI will require that a protocol be submitted tothe Agency for review and approval prior to conduct of the study.2EPA has received a request to terminate the use of triclosanin agricultural films and mulches. If the cancellation order becomes effective and all product labelsare amended to remove the use, this anticipated data requirement should no longer be needed.3This study, previously held in reserve in the RED, is expected to be required for registration review (see Appendix C).4Study held in reserve in the RED pending the outcome of textile and plastic manufacturing studies.5An acute value is expected to be required for the same species used in the fish full life cycle test to allow calculation of an acute-to-chronic ratio (ACR) for usein predicting a chronic value for the mostacutely sensitive freshwater species.Docket Number: EPA-HQ-OPP-2012-0811Page19of116Table 7 –Data Needs Required by the Data Call-In for the Triclosan REDGLNStudy NameTest SubstanceTime Frame(Measured inmonths fromDCI Receipt)Risk Assessment(s)Data Will SupportUse Site(s) Triggering DataRequirementApplicable ExposureScenario850.1730 Fish BCF PAIRA; TGAI 12Environmental Fate,EcologicalResidential and public accesspremises; materials preservatives;aquatic non-food industrial use850.1710 Oyster BCF PAIRA; TGAI 12 EcologicalResidential and public accesspremises; materials preservatives;aquatic non-food industrial use850.18501Aquatic Food ChainTransferPAIRA; TGAI 24 EcologicalResidential and public accesspremises; materials preservatives;aquatic non-food industrial use835.4400Anaerobic AquaticMetabolismPAIRA; TGAI 24 Environmental FateResidential and public accesspremises; materials preservatives;aquatic non-food industrial useSS-1Surface WaterMonitoring (textile,plastic manufacturing)MP; PAI; TGAI 24 EcologicalResidential and public accesspremises; materials preservatives;aquatic non-food industrial useSS-2Chronic SedimentToxicityMP; PAI; TGAI 24 EcologicalResidential and public accesspremises; materials preservatives;aquatic non-food industrial use875.1200Indoor Exposure,DermalMP; EP 24 Occupational Materials preservatives Powder pour875.1400Indoor Exposure,InhalationMP; EP 24 Occupational Materials preservatives Powder pour875.1600Application ExposureMonitoring DataReportingALL 24Occupational andResidentialMaterials preservatives; aquaticnon-food industrial useLiquid pour studyresults875.1700Product UseInformationALL 12 All All AllDocket Number: EPA-HQ-OPP-2012-0811Page20of116875.2300Indoor SurfaceResidue DissipationEP 24 ResidentialMaterial preservative use inplastics (toys)Mouthing plastic toys875.2700Product UseInformationALL 12 All All All875.2800Description of HumanActivityALL 12 All All All875.2900DataReporting/CalculationsALL 24 ResidentialMaterial preservative use inplastics (toys)Surface residue study(plastic toy) resultsSource of post-RED DCI: EPA Docket EPA-HQ-OPP-2007-0513-0066, GDCI 054901-301971Study held in reserve in the RED pending the outcome of surfacewater monitoring studies, the fish bioconcentration factor, andthe oyster bioconcentrationfactor studies.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 21 of 116 

## 3 Human Health Risk Assessment

3.1 Existing Toxicological Endpoints

The endpoints listed in Table 8 were used in the human health risk assess ments for the Triclosan RED. All information, including existing toxicol ogy studies, valid scientif ic literature and the studies that are expected to be required for regist ration review will be considered in the final risk assessment for OPP.

Summary information on the interaction of tr iclosan with the endocrine hormone system, including interaction with the thyroid, estroge n, and androgen hormone sy stems, was included in the 2008 RED. As part of the registration review, these data about interact ion of triclosan with the endocrine system will be incl uded in the risk assessment.

With respect to human health risk assessments, th e petition raised the issue of whether triclosan may result in human exposure to dioxins. The Agen cy will evaluate available information to determine the extent to which this registrati on review will address pot ential 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

Short-Term/IntermediateTerm 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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 22 of 116 Exposure Scenario Dose Used in Risk Assessment Uncertainty factors for Risk Assessment Study and Toxicological Effects
Dermal (shortterm) 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 (longterm) 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.

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 phosphatase Cancer (oral) In accordance with the EPA Final Guid elines 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 [s pecial 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 = margin of expo sure, LOC = level of concern, NA = Not Applicable



### 3.2 Dietary Exposure

The use of products containing triclosan ma y result in indirect dietary exposure, i.e. exposure to food as a result of the use of triclosan in paper, adhesives, countertops, cutting boards, icemaking equipment, and conveyor belts. Thes e uses were assessed in the 2008 RED and no dietary risks of concern were id entified. Potential secondary (or indirect) dietary exposure for this registration review will be included in the aggregate assessment (see 3.4.1) based on the National Health and Nutrition Examination Su rveys (NHANES) biological monitoring data because these data refl ect all exposures.

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### 3.3 Occupational and Residential Exposures

Representative occupational handler exposures were assesse d 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 Ma nufacturers Association (CMA) Antimicrobial Exposure Study (USEPA, 1999) and the Pesticide Handlers Exposure Database (PHED; USEPA, 1999) were used to assess handler risk. Use of tric losan as a material pres ervative in paint was found ineligible. The registrant re quested voluntary cance llation. The paint uses for tricosan 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.

3.3.1 Occupational Handler Exposures

EPA anticipates the need to conduct an occupa tional exposure assessment on the HVAC use and on open 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 expect ed to occur, a residential handler exposure assessment is not anticipated fo r this registration review.

3.3.3 Residential Post-Application Exposures Residential post-application expos ure 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 mi gration 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 uses such as toothpas te, hand soaps, and deodorants.

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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 24 of 116 For the 2008 RED, EPA conducted the residentia l post-application expo sure assessment for triclosan using the biomonitoring data availabl e through NHANES. This approach was adopted by EPA because of the need to assess aggregat e 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 expos ures to daily use products. In the case of triclosan, population-based biologic al monitoring data are available to assess the co-occurrence of uses to develop an aggregate exposure assessm ent for ages 6 years and older. The populationbased biological monitoring data are the best predictor of a ggregate exposure because not only are the data triclosan specific, they are also ba sed on actual consumer use of the various triclosan products as they co-occur in practice and would include drinking water exposures as well. EPA intends to use the latest available NHANES biom onitoring data for assessment of residential post-application exposures to triclosan in the registration 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 nonoccupational ( i.e. residential) pesticid e exposures. An aggregate exposure assessment for triclosan was presented as part of the background docum entation for the 2011 FIFRA SAP meeting using the NHANES database.

For this registration review, EPA plans to conduct an aggreg ate assessment to account for exposure to triclosan from diet ary and residential post-applica tion exposures. The aggregate assessment will estimate risk based on the aggreg ated exposure of EPA and FDA uses using the NHANES biological monitoring data. The NHANES databases are a series of U.S. national surveys of the health and nutrition status of the non-institu tionalized civilian population conducted by the Centers for Disease Contro l and Prevention (CDC). EPA believes the NHANES dataset provides the most comprehens ive data on exposure to triclosan from all sources (dietary and non-dietary as well as both EP A- and FDA-registered uses) and is the best dataset for estimating aggregate ri sk to triclosan. These data ac count for both indirect dietary exposures and exposures through drinking water mo re effectively than the standard models normally used by the Agency 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 regu lated 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 data were available for triclosan only for the 2003- 2004 survey cycle. Subsequently, CDC has re leased 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 triclosan exposure.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 25 of 116 Although the aggregate exposures presented using the NHANES data are considered to include all triclosan exposures, it does not include exposures to childre n under the age of 6 years old. Children under the age of 6 year s exhibit unique activities that do not occur at older ages. Therefore, a separate estimate for children under 6 years old will be includ ed in the registration review risk assessment.

3.4.2 Cumulative Exposures Unlike other pesticides for which EPA has fo llowed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for triclosan and any other substances. For the purpose s of this registration review, therefore, EPA has not assumed that triclosan has a common mech anism of toxicity with other substances. For information regarding EPA’s efforts to determ ine which chemicals have a common mechanism of toxicity and to evaluate th e cumulative effects of such chem icals, see the policy statements released by EPA’s Office of Pesticide Program s concerning common mechanism determinations and procedures for cumulating effects from s ubstances 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 onl y addressed acute risk to freshw ater fish and aquatic plants. Exposure to aquatic organisms was based on monito ring data reported in th e published literature, including U. S. Geological Survey (USGS) mon itoring data for U. S. waterways, and from down-the-drain modeling. However, the waterw ay concentrations in clude all sources of triclosan, not just antimicrobial uses. To eval uate 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 sp ecifically designed to monitor the pesticidal textile and plastic manufacturing uses were called-in as pa rt of the post-RED DCI (GDCI 054901-30197, October 5, 2011).

The Agency has not conducted a risk assessmen t that supports a complete endangered species determination for triclosan. The ecological risk assessment planned duri ng registration review will allow the Agency to determine whether uses of triclosan have 'no effect' or 'may affect' federally listed threatened or endangered specie s (listed species) or their designated critical habitats. When an assessment concludes that a pe sticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will c onsult with the U.S. Fish and Wildlife Service and/or National Marine Fi sheries Services (the Services), as appropriate.

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### 4.1 Environmental Conceptual Model Exposure Pathways The triclosan use scenarios with potential fo r environmental exposures of concern include material preservative uses which result in disc harge to waste water trea tment plants such as application to textiles. No environmental exposure from the application of triclosan to plastic is expected because the label prohib its use in processes which would result in contact and transfer of triclosan with process water that would be di scharged 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. The conceptual models for uses with potential environmental exposure are in Figure 1 and Figure 2 4



### .

4 EPA has received a request to terminate the use of triclo san in agricultural films and mulches. If the cancellation order becomes effective and all product labels are amended to remove the use, these conceptual models will be adjusted accordingly.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 27 of 116 Figure 1 - Conceptual Model fo r Environmental Exposure from Treatment of Textiles with Triclosan

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 TreatedTextiles

Washing/Leaching

### Docket Number: EPA-HQ-OPP-2012-0811

Page 28 of 116 Figure 2 - Conceptual Model for Environmenta l 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 di rect and indirect effect s to biological receptors. Acute and chronic toxicity data from studies submitted by pesticide registrants along with the available open literature will be used to evalua te the potential direct and indirect effects of triclosan to aquatic and terrestri al receptors. Current select ed ecotoxicological endpoints are summarized in Table 10. A more detailed descripti on of the ecotoxicity studies is provided in Appendix C.

4.2.1 Mechanism of Action IFDA (2008) identifies that triclosan has two me chanisms of action. One mechanism is via insertion into bacterial cell membranes and disr uption of membrane activities without causing leakage of intracellular component s. The second mechanism of ac tion is inhibition of bacterial fatty acid synthesis at the enoyl-acyl carrier protein reductase ste p. Fatty acid synthe sis is critical for building of cell membranes and reproduction. This enzyme is found in bacteria, fungi, and

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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 29 of 116 some plants. In algae triclosan has been obs erved to compromise lipid biosynthesis, cell membrane integrity and photosynthesis.

4.2.2 Measures of Effect (Ecotoxicology Endpoints) Current selected ecotoxicologica l endpoints for conducting the risk assessment are provided in Table 10. All available ecotoxicity endpoints from studies submitted by registrants are tabulated in Appendix C. The Agency rec ognizes that there are addition al data available on triclosan effects in the open literature. Part of the analysis plan includes a literatu re search and review of such data for inclusion in the risk assessment as needed. The Agency uses the most sensitive acceptable toxicity values for a ssessing risk to each receptor group. Endpoint data gaps are indicated.

No endpoints were selected for dioxin or met hyltriclosan transformation products. From a preliminary examination of which dioxins are form ed from triclosan in chlorinated waters (2,7- dibenzodichloro- p -dioxin; 2,8-dichloro- p -dioxin; 1,2,8- and 2,3,7-tr ichlorodioxins and 1,2,3,8- tetrachlorodioxin), they are not among congeners of toxicological con cern (see Appendices B and E) and no endpoints were selected for the as sessment. Additionally, methyltriclosan was not detected in effluent monitoring studies for te xtiles and therefore no endpoints are included.

Table 10 - Effects Endpoints for the Ec ological 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 = 288 a μg ai/L 43969301

Rainbow
trout Chronic Fish full life cycle data 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 required Plan to modelfrom acute-tochronic ratios (ACRs). Estuarine/marine Shrimp or Acute Data required

### Docket Number: EPA-HQ-OPP-2012-0811

Page 30 of 116 Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Comment Reference/ Study Classification invertebrates oyster Chronic Data required
Estuarine/marine benthic invertebrates Chronic Data not required NA

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 44422801

NOAEC Not determined

Birds Mallard Acute LD 50 = 822 mg ai/kg bw 43022602
Chronic Not required NA

Mammals Rat Acute LD 50 >5000 mg/kg 43206901

Chronic NOAEC = 50 mg ai/kgbw/day 40623701
Nontarget insects Acute Not required N/A

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

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### 4.3 Exposure Analysis Plan

4.3.1 Aquatic and Terrestrial W ildlife Exposure Estimates In order to address the risk hypot hesis, estimates of environmen tal exposure based on the textile and the in-service use of agricultural mulch conceptual models will be estimated. For in-service use of agricultural mulch impregnated with triclosan, PRZM/EXAMS will be used to estimate runoff and loading to surface water from agricult ural fields covered with agricultural mulch impregnated with triclosan and fate in surface water 5 

### . No information on the leach rate from plastic agricultural mulch is available for use in PRZM modeling. Cons ervative estimates of triclosan leaching from plastic, such as 100% leaching, will be used unless information on leaching from plastics is submitted or found from ope n literature to refine estimates of leaching. In the RED, monitoring data was used to character ize risk from pesticidal uses but it was also recognized that the available monitoring data wa s not specifically desi gned to identify exposure specifically from pesticidal ( e.g ., material preservative) uses but was more likely to reflect FDA permitted uses. Monitoring data specific to material preservative 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 assessme nt. This monitoring data will be used to characterize exposure for use in the registration re view. 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 in th e re-registration requirements for triclosan, EPA required 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-d ischarging (holding valid NPDES Permits) textile manufacturi ng facilities, using triclosan as a material preservative, were used to determine the concentration of triclosan in textile manufacturing effluent. Environmental International Corporation on behalf of Microba n International, Ltd conducted monitoring in 2012. Two textile facilities were chosen to collec t data on the concentrat ions of triclosan and methyl triclosan present in their effluent afte r 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 te mperature. The spent or remaining solution from the exhaustion process is discharged to on-site wastewater treatment plants be fore the resulting effluent is discharged to surface waters. The discharge to surface waters at these facilities is conducted under National Pollutant Discharg e Elimination System (NPDES) permits. Sampling intervals and frequencies were determined based on faci lity production operations, wastewater treatment operations, and the hydraulic reten tion times for the unit processes, ensuring that the effluent

5 EPA has received a request to terminate the use of triclo san in agricultural films and mulches. If the cancellation order becomes effective and all product labels are ame nded to remove the use, this section will be updated accordingly.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 32 of 116 samples would be representative of facility effl uent during triclosan-impregnation operations. Additional WWTP process parame ters collected during the sa mpling periods provided support that WWTPs were operating normally during samp ling periods. The triclosan use pattern and WWTP characteristics for these two facilities ar e summarized in Table 11. Results from the monitoring, which are summarized in Table 12 wi ll be used to charac terize discharge and 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 (specifically 7Q10 flow 6 

### ).

Table 11—Textile Facility Characteristics Du ring the Triclosan Monitoring Studies

Characteristic Facility # 1 Facility # 2 Notes Triclosan application pattern during study Intermittently used Constantly used -- Number of operating days during study triclosan was used 15 11

Amount (lbs) of triclosan applied during 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 (nutrientsdehydrated) 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

6 "The streamflow that occurs over 7 consecutive days and has a 10-year recurrence inte rval period, or a 1 in 10 chance of occurring in any one year. Daily streamflow s in the 7Q10 range are gene ral indicators of prevalent drought conditions which normally cover large areas. 7Q10 va lues are also used by the State for regulating water withdrawals and discharges into streams." (USGS)

### Docket Number: EPA-HQ-OPP-2012-0811

Page 33 of 116 Characteristic Facility # 1 Facility # 2 NotesAeration lagoon mixedliquor 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: milli on gallons per day; Max: maximum; Min: minimum; NR: not reported; WW: wastewater (1) 

### Biological treatment stage

Table 12—Triclosan and Methyl Triclosan Monitoring Data from Two Textile Manufacturing Facilities

Facility Triclosan Concentration (ng/L) Methyl Triclosa n (ng/L) Whole Effluent (1) 

### Effluent Supernatant (2) 

### In-Stream 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 (1.8- 1.9) No. 2 138 180 130 88.8 110 84 33.1 43.2 ND (1.8)
(1) 

### Collected from effluent channel. Facility #1: five consecutive, 24- hour composite effluent samples. (2) 

### Supernatant from sample subject ed to centrifugation at 100,000 ms -2

(3) 

### In-stream wastewater concentration (IWC) f actor 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.



### 4.4 Effects Analysis Plan Open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database 7



### , which employs a literature search engine for lo cating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The ECOTOX databa se will be searched when the risk assessment

7 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.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 34 of 116 for triclosan is prepared. Endpoi nts more sensitive than those al ready selected will be reviewed for use in the risk assessment.



## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its reregistration decision for triclo san, 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 subject to the endocrine screening part of the Endocrine Disruptor Screenin g Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must scre en all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredie nts. Triclosan is not among the group of 58 pesticide active ingredients on the in itial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call-ins, requiring the submission of EDSP screening assays for triclosan. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 scr eening battery, please visit our website: http://www.epa.gov/endo/.

### Docket Number: EPA-HQ-OPP-2012-0811

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## 6 Guidance for Commenters

6.1 Preliminary Work Plan

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

6.1.1 Trade Irritants

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any tr ade irritant issues resulting from lack of Maximum Residue Limits (MRLs) or disparitie s between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the na ture of the concern.

6.1.2 Water Quality

Triclosan is not identified as a cause of impairme nt for any water bodies li sted as impaired under section 303(d) of the Clean Water Act, based on information provided at the Agency’s National Pesticides Cause of Impairment of Wa ters website (searched February 22, 2013) 8,9 

### . In addition, no Total Maximum Daily Loads (TMDL) have been developed for triclosan, based on information provided at the Agency’s National Pe sticide TMDL web site (searched February 22, 2013) 10 

### . More information on impaired water bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/. The Agency invite s submission of water quality data for this pesticide. To the extent possible, data should co nform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclus ion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Revi ew Risk Assessment and Management Process (see: http://www.epa.gov/oppsrrd1/regist ration_review/water_quality_sop.htm) , in order to ensure the data can be used quantitatively or qualit atively in pesticide risk assessments.

From a preliminary examination of which dioxins 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 co ngeners of toxicological concern (see Appendices B and E). Dioxin conge ners considered of environmen tal toxicological concern are listed in Table 34. Because the dioxin congeners ar e not those of concern, a search of impaired waters due to dioxins of environmental concern was not performed for triclosan.

8 . http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885
9 http://iaspub.epa.gov/waters10/attains_na tion_cy.control?p_report_type=T#causes_303d
10 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant _group_name=PESTICIDES

### Docket Number: EPA-HQ-OPP-2012-0811

Page 36 of 116 6.1.3 Environmental Justice

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to triclosa n compared to the gene ral population. Please comment if you are aware of any sub-populatio ns that may have atypical, unusually high exposure compared to th e general population.

6.1.4 Structure Activity Relationships

EPA must rely upon information of appropriate qu ality and reliability for each decision made by the Agency. In the Office of Pesticide Program s (OPP), the evaluation process for a pesticide chemical traditionally begins with the applicant’ s submission of a set of studies conducted with the specific pesticide chemical of interest. The us e of the results of such testing (measured data) is a logical, scientifically rigorous proce ss that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

Today, there is significant intere st in alternative techniques, i.e. , techniques other than data generation that could significantly inform the Agency’s decision-making process. Recently, OPP has made increasing use of stru cture activity relationship (SAR ) as part of its regulatory decision-making process. In the SAR process, a ch emical's molecular structure is compared to that of other chemicals for which data are availabl e. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties. Thus, the chemical’s physical, chemical, and biol ogical properties are a f unction of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a selected set of measured da ta on a single physical, chemical, or biological property is used to derive a model (an equatio n) to predict the valu e of that property.

Since SAR assessments and QSAR modeling are anothe r set of tools that are available to Agency scientists, OPP has begun a proce ss shift that envisions shifting from the current study-by-study approach to an approach in which the use of pr edicted data, generated us ing validated models, is considered along with information from open litera ture and studies specifically generated under Part 161 requirements. All relevant information w ould be considered as pa rt of a weight-of-theevidence evaluation.

At this time, EPA believes that for certain e ndpoints, especially physi cal/chemical and fate properties, that SAR and QSAR might be effect ively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals. When considering biological prope rties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is appropriate because the risk assessment for lo wer toxicity chemicals can be stream-lined, i.e. , a

### Docket Number: EPA-HQ-OPP-2012-0811

Page 37 of 116 screening-level assessment procedure rather than multiple tiers of assessments with progressively more data requirements.

If stakeholders believe that submission of predic ted data can fulfill one of the data needs for the triclosan case, then the Agency invites submi ssion of this information. The submitter would be expected to supply a rationale describing th e utility of the information and provide documentation on the scientific va lidity of the information. The de termination that the predicted data fulfills the data requirement would be at the sole discretion of the Agency. Pre-submission consultation with the Agency is encouraged.

6.1.5 Additional Information

Stakeholders are also specifically asked to provid e available information a nd data that will assist the Agency in refining its risk assessments, including any species-spec ific ecological effects determinations. The Agency is interested in receiving the following information:

1. Confirmation on the following label information: A. Sites of application B. Formulations C. Application methods and equipment D. Maximum application rates E. Frequency of application, applicatio n intervals and maximum number of applications F. Geographic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non-agricultural uses ( e.g. , materials preservation) 5. Typical application interval 6. State or local use restrictions 7. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency 8. Monitoring data



## 7 Next Steps

After the close of the 60-day comment period in May 2013, the Agency will review and respond to any comments received in a timely manner, and then issue a Final Work Plan for the Triclosan

case.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 38 of 116 

## 8 References

Ellis DD et al ; Arch Environ Contam Toxicol 11: 373 - 82 (1982). Environmental Protection Agency. High Production Volume Information System (HPVIS). http://www.epa.gov/hpvis/

Miller et al ; Estogenic Activity of Phenolic Additives Determined by an In Vitro Yeast Bioassay, 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 Chemic als Associated with Estrogenic Activity, Journal of Biologi cal Chemistry, Volume 272, Issue 6, pp 3280- 3288, February 7, 1997.

Soto, AM et al : The E-Screen Assay as a Tool to Iden tify Estrogen - An Update on Estrogenic Environmental Pollutants, Environmental Health Perspectives,Vol. 103, Supplement 7, pp 113-122, October 1995

Tollefsen et al ; Estrogenicity of Alkylphe nols and Alkylated Non-Phe nolics in a Rainbow Trout ( Oncorhynchus mykiss ) Primary Hepatocyte Culture. Ecotoxicology and Environmental Safety 71, pp 370-383, 2008.

United States Food & Drug Administration (FDA) . 2008. Nomination Profile Triclosan [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 93-115, 2003.

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# APPENDIX A: Toxicology Profile

Hazard/Toxicity

Acute Toxicity for Product Labeling

A complete database of acute toxi city data for triclosan was available to the Agency 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 expe rimental animals with t echnical grade triclosan show that by the oral and dermal routes, triclosan is of low acute toxicity (Toxicity Category IV; MRIDs 43206501 and 94044). By the inhalation rout e 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 e xposures (MRID 42306902 and 43310501). Triclosan produces moderate irritation to the eyes (MRID 94045) and skin (MRID 42306903) with a Toxicity Category III assigned for both for acu te exposures. Triclo san was not a dermal sensitizer in guinea pigs usi ng 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 IrritationRabbit Triclosan (97% ai) 94045 moderately irritating II

870.2500

(§81-5) Primary Dermal IrritationRabbit Triclosan (% ai not provided) 42306903 PII: 3.5 at 72 hours III

870.2600

(§81-6) Dermal SensitizationGuinea Pig Triclosan (99.7% ai) 43206502 Not a Sensitizer NA

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Page 40 of 116 

### Non-Acute Toxicity

The toxicology database for the tr iclosan registration review case is comprised principally of studies that were available to the Agency when the RED was written in 2008. Additional published research on triclosan co mpleted after 2008 is also incl uded in the table below. These data were included as part of the bac kground 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 Discip linary Chapter in support of the RED in regulations.gov in docket number EPA-HQ-OPP-2007-0513-0036.

Table 14 - Non-Acute Toxicity Studies for Triclosan

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 (nonrodent) 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 Triclosan 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% 44389708Acceptable - NonGuideline 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% 44389710Acceptable - NonGuideline 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 NOAEL: 3.0 mg/animal/day

### Docket Number: EPA-HQ-OPP-2012-0811

Page 41 of 116 Guideline Number/ Study Type/ Test Substance (% ai) MRID Number (Year)/ Citation/ Classification/ Doses Results

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 Determined (> 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.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 42 of 116 Guideline Number/ Study Type/ Test Substance (% ai) MRID Number (Year)/ Citation/ Classification/ Doses Results

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)CarcinogenicityMouse 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 Triclosan 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.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 43 of 116 Guideline Number/ Study Type/ Test Substance (% ai) MRID Number (Year)/ Citation/ Classification/ Doses Results

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 ug/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 tester 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 3ug/mL (18-hour harvest) induced a doserelated 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 concentration 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.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 44 of 116 Guideline Number/ Study Type/ Test Substance (% ai) MRID Number (Year)/ Citation/ Classification/ Doses Results

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 effect 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, administration 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.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 45 of 116 Guideline Number/ Study Type/ Test Substance (% ai) MRID Number (Year)/ Citation/ Classification/ Doses Results

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 excretory 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); fecal 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 occurred 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 could 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.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 46 of 116 Guideline Number/ Study Type/ Test Substance (% ai) MRID Number (Year)/ Citation/ Classification/ Doses Results

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-fold within 24 hours. For dogs, somewhat greater blood t max values were observed but were variable (2-8 hours) for the two dogs tested. Timecourse analysis of tissues from mice given a single intravenous dose (10 mg/kg) of 14 Ctriclosan 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 elimination 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.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 47 of 116 Guideline Number/ Study Type/ Test Substance (% ai) MRID Number (Year)/ Citation/ Classification/ Doses Results

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 triclosan, 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 dose. 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.

Repeated 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 and a higher conjugating/metabolizing capacity at approximately 200 mg/kg, as compared to approximately 2 mg/kg.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 48 of 116 Guideline Number/ Study Type/ Test Substance (% ai) MRID Number (Year)/ Citation/ Classification/ Doses Results

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 three 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 postdosing. 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 unchanged triclosan. Up to 75% of the urinary radioactivity underwent spontaneous hydrolysis presumably due to endogenous urinary β -glucuronidase. 870.7600 Dermal Absorption rabbit 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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 49 of 116 Guideline Number/ Study Type/ Test Substance (% ai) MRID Number (Year)/ Citation/ Classification/ Doses Results

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 except 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 several biochemical parameters in the liverat the 6000 ppm dose level. Cytochrome P450 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 level 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 enzyme 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.

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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 50 of 116 Guideline Number/ Study Type/ Test Substance (% ai) MRID Number (Year)/ Citation/ Classification/ Doses Results

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 the 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 is 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 inferred 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), triclosan 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 estr ogen receptor of human MCF7 breast cancer cells by triclosan and inhi bition 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 shown to have anti-androgenic 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. Us ing a mouse mammary tumor cell line with a

### Docket Number: EPA-HQ-OPP-2012-0811

Page 51 of 116 stably-transfected androgen reporter gene (LTR -CAT), induction of CAT activity by testosterone was inhibited in the pres ence of triclosan at 10 -5 

### M and above. The prolifer ative response of these mouse mammary tumor cells to testoster one was also inhibited by triclosan.

Ahn et al . (2008) examined the biologi cal activity of triclosan in in vitro , cell-based, and nuclear receptor-responsive bioassays for the aryl hydr ocarbon (Ah), estrogen (E), and androgen (A) receptors. As reported in the study, tr iclosan at a concentration of 10 μ M induced luciferase expression to 40% of that seen with 2,3,7,8-te trachloro dibenzo-p-di oxin (TCDD), but it inhibited the induction of luciferase expr ession by TCDD by approximately 30%. These agonist/antagonist results are consistent with TCS being a partial agonist of the Ah receptor. In both the ER- and AR-responsive bioassays, triclosan exhibited antagonistic ac tivity in this study.

Chen et al . (2007) examined the anti-andr ogenic potential of triclosa n using a cell-based stably transfected cell line lacking critical steroid me tabolizing enzymes. Triclosan alone exhibited no androgenic activity at con centrations up to 10 μM, but transcrip tional activity in the presence of 0.125 nM testosterone was inhibited by 10 μM triclosan by 92%, and by 38.8% at 1.0 μM triclosan.

Estrogenic Effects

Tamura et al . (2006) studied the androgen receptor (AR) activity of listed chemicals, so called SPEED 98, by the Ministry of the Environment, Japan, and structurally related chemicals was characterized 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 stru ctures were capable of disrupti ng the endocrine systems mediated 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 based on in vitro MDA-kb2 reporter gene assay.

Stoker et al . (2010) examined the potentia l estrogenic effect s of triclosan using the rat weanling uterotrophic assay, an assay for detection of uter ine 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 triclo san). However, there was a significant dosedependent increase in the mean uterine wet a nd blotted weight in th e 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 response by enhancing the activity of exogenously administered estrogen and not by a direct stimulation of the estrogen receptor, as triclosan doses as high as 300 mg/ kg without cotreatment with EE di d not alter uterine weight or histology.

Effects on Thyroid

### Docket Number: EPA-HQ-OPP-2012-0811

Page 52 of 116 Recent in vivo data from rats provides evidence th at 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 di scussed the possibility of more than one mechanism involved in the decrease of T4 leve ls 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.

The effect of triclosan on thyroid has also been investigated using the pubertal assay (US EPA, 2008). Weanling male rats were dosed by oral gava ge for 30 days starting on postnatal day 23 with 0, 3, 30, 100, 200 or 300 mg/kg/day of tric losan. 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 de creased at 200 mg/kg, wh ile thyroid stimulating hormone (TSH) levels were unaffect ed at any dose level. Thyroi d histology was also not altered at 100 and 200 mg/kg. Histology at 300 mg/kg is currently unde r examination. Mean liver weight of dosed male rats was increased si gnificantly at the 100 mg/kg dose and above, suggestive of hepatic enzyme induction and incr eased 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 leve ls observed in juvenile rats in this study was not investigated. Mean liver weig ht of dosed male rats was in creased 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 i nduction of liver UDP-glucu ronyl transferase 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 consecuti ve 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 le vels 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 resp ect to the pharmacodynamics of triclosan, the pharmacokinetics of triclosan, which has been studi ed in several animal species and in humans, shows similar half-life of elimination in experi mental animal species studied (rat, hamster, mouse) in comparison to humans. It has been ob served, however, that en terohepatic circulation of triclosan occurs in the rat, and that a si gnificant first-pass eff ect occurs in humans. Comparison of comparable oral doses administer ed to rats and humans shows smaller area under the curve (AUC) values for humans compared to rats, suggesting less overall systemic exposure. In addition, it is also known that the rat is a more sensitive spec ies than the human with respect

### Docket Number: EPA-HQ-OPP-2012-0811

Page 53 of 116 to perturbations in thyroid homeostasis, based on the shorter half-life of T4 in the rat (12-24 hours) compared to humans (5-9 days), and th e lack of the high affinity binding protein thyroxine binding globulin in rats (Capen, 1996).

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Page 54 of 116 

# APPENDIX B: Environmental Fate

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

Under aqueous conditions because triclosan ha s 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 nonionized state is generall y the more bioavailable and toxic form. As the pH of soil or water becomes higher or more basic, triclosan is more likely to be negativel y-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 aqua tic 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 wastew ater treatment is likely to remove more than 80% of triclosan and that under anae robic conditions concentrations in sludge can be expected to increase because the sludge is degrading faster than triclosan. The prim ary degradation products in chlorinated water treatment include 4-chloro triclosan, 6-ch loro triclosan, and 4,6-dichloro triclosan. These open literature studies will be formally reviewed by the Agency during registration review.

A detailed discussion of environmental fate prop erties of triclosan and its major transformation products methyl triclosan (methoxy triclosan), 2, 4-dichlorophenol, chlorinated triclosan (4- chloro-, 6-chloro-, and 4,6-dichloro-), a nd the predominant dioxins such as 2,7/2,8- dichlorodioxin based on these s ources is provided in this appe ndix. For exposure modeling, a total toxics residue approach will be used in the risk assessment. This means that estimates of exposure will include consider ation of both parent and it s major toxic degradates.

Methyl triclosan (methyoxy triclosan) is formed by microorganisms in the presence of oxygen. It has been observed to form at significant (> 10 %) of applied triclosan in aerobic soil (nonflooded top layer of soil) and in WWTPs to a lesser extent.

Chlorophenol compounds (2,4-dichloro, 4,6-dichlo ro-, 2,6-dichloro-, and 2,4,6-trichloro) are formed as a result of photodegradation in water (43022608, acceptable study) and the combination of photodegration in water and aqua tic metabolism (Buth, 2009). In the Buth (2009 article), dioxins were formed at approxima tely 1,000X less than th e parent triclosan concentration. The Buth (2009) article will be fo rmally reviewed in Registration Review.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 55 of 116 Chlorinated triclosan (4-chloro-, 6-chloro-, a nd 4,6-dichloro-) were form ed in the Buth (2009) study as a result of chlorination of wastewater. The Buth (2009) article will be formally 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-dichlo rodioxin, 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 formed in these studies, they are not among the congeners of c oncern for humans or ecological receptors ( i.e ., have no 2,3,7,8-tetrachlorodibenzo- p -dioxin (2,3,7,8-TCDD) toxicity equivalency factors 11



### , 12 

### . Appendix E contains a list of the 17 congeners of ecological concern.

To 

### refine estimates of exposure concentrations in surface waters from textile and plastic material preservative use sites, monitoring of textile and plastic material preserva tive 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 industrial pr ocess water. Such a lack of cont act means there is no environmental exposure pathway for aquatic and terrestrial wildlife. Because th ere are those plastic manufacturing processes where the plastic does come into contact with industrial process water, the label has been changed to limit the use of tr iclosan as a material preservative to plastic manufacturing that does not come into contact with process wate r. Monitoring at two textile facilities was recently completed and submitted to the Agency for review (MRID 48858101). The results of this study showed that average and maximum in-stream wastewater concentrations (IWC) for facility 1 were: 3.2 ng/L and 6.1 ng/L re spectively for triclosan and methyl-triclosan. The average and maximum IWC for facility 2 were: 33.1 ng/L and 43.2 ng/L respectively for triclosan and methyltriclosan. The study was found to be acceptable.

To eliminate unnecessary decimals in values, mo st concentration units in this document are expressed either as nanograms/lite r (ng/l) for liquids, nanograms/gram (ng/g) for solids (mostly sludge), or pg/g for solids (dioxins in sediments). These units translate to parts-per-trillion (ppt) for liquid [1 x 10 -10 

### %], parts-per-billion (ppb) for sewage sludge [1 x 10 -7 

### %], or parts-pertrillion for dioxin in sediments.

The physical-chemical properties of triclosan re veal that triclosan has relatively low water solubility (12 ppm or mg/l), a relatively low va por 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) significantly (criteria for non-volatility is vapor pressure <10 -6 

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

11 http://www.epa.gov/raf/files/tefs-for -dioxin-epa-00-r-10-005-final.pdf
12 http://www.epa.gov/raf/tefframework/index.htm

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Page 56 of 116 a chemically-neutral (non-electri cally-charged) form in acidic and neutral pH conditions and a charged state under more basic or alkalin e conditions because the pKa is 8.14 (MRID 42027904). At pH values equivalent to the pKa half of the triclosan is neut ral and half is in a charged state, as the pH drops below the pKa va lue 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 usually less toxic than the neutral state of a compound. As the pH of the soil increases, both the soil/sediment and tr iclosan become more ne gatively-charged and the like charges will lead to more association with water in the presence of soil and sediment.

The Agency has received and summarized numer ous peer-reviewed literature studies on the environmental fate of triclosan following the pub lication of the RED. Given the wide range of values and varying information, the Agency anti cipates reviewing critical environmental fate data before publication of the FWP.


## Abiotic degradation of Triclosan and Transformation Products

The Agency has received studies on hydrol ysis (835.2120) and photodegradation in water (835.2240) that satisfy these data requirements. Th e studies demonstrate that triclosan is stable to abiotic hydrolysis but degrad es 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 st udy (MRID 43022608), triclosan degraded with a half-life of 41 minutes and formed the degradat e 2,4-dichlorophenol (2,4-DCP) which reached 97 % of the applied parent compound and was stable . Photodegradation in water is expected to be the primary route of dissipati on for triclosan in shallow, we ll-mixed water with no suspended or bottom sediment. However, this route of di ssipation in water will be limited in nature by water depth and light attenuation, suspended sediment, shading, and sorption to bottom sediment.

Six aqueous photoloysis st udies were found in the literature, and are also cited in Table 15. These studies will be reviewed as part of the re gistration review action because they appear to provide additional information on longer half-lives in the environment as well as the presence of additional degradation products such as dioxi ns and dichlorohydroxydi phenyl 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-TC DD) toxicity equivalency factors 13,14 

### ). Table 15 also includes a predicted half-life fo r photodegradation in ai r (835.2370) which is not anticipated to be critical for the risk assessment because triclo san 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 

### ).

13 http://www.epa.gov/raf/files/tefs-for -dioxin-epa-00-r-10-005-final.pdf
14 http://www.epa.gov/raf/tefframework/index.htm

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Page 57 of 116 Table 15 - Abiotic Degradation of Triclosan and Degradate Formation

Parameter Half-lives (parent triclosan unless specified) Source/ Study Classification/ Comments Hydrolysis (OPPTS 835.2120, 161-1) pH 4 pH 7 pH 9 Stable at 50°C MRID 42027908 Supplemental (preliminary study only), but no additional data expected to be required

MRID 00046300 not revi ewed because it only addressed theories of dioxin formation Aqueous photolysis (OPPTS 835.2240, 161-2) Guideline study 41 min 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 Latch et al ., 2004 Deionized water and Suwanee River water in U.S. 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) Sanchez-Prado et al ., 2006 Irradiated wastewater samples in Spain

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 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 freshand salt-water (study length of 120 days). 2,8-DCDD reached 60 and 90 % of triclosan in fresh- and salt-water

### Docket Number: EPA-HQ-OPP-2012-0811

Page 58 of 116 Parameter Half-lives (parent triclosan unless specified) Source/ Study Classification/ Comments 23 hours (deionized water) 18 hours (wastewater) Mezcua et al ., 2004 Quality unknown, study not formally reviewed.

Photodegradation of triclosan in water and wastewater in Spain 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 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-chloro triclosan, 6-chloro triclosan, and 4,6-di chlorotriclosan 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 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 Agency has received acceptable studies on laboratory aerobic soil metabolism (835.4100), anaerobic soil metabolism (835.4200), anaerobi c aquatic metabolism (835.4400), and aerobic aquatic metabolism (835.4300). These laboratory studies provide a measure of the biotic degradation potential of a com pound in the environment, without the bias from dissipation by

### Docket Number: EPA-HQ-OPP-2012-0811

Page 59 of 116 leaching. Triclosan was found to degrades rapidly in the presence of oxygen in the top layer of soil, but be stable under anaerobic conditions (lack of oxygen) and in aquatic conditions. The transformation product methyl triclosan (methoxy triclosan) was formed at up to 17.5 % of applied triclosan. The aerobi c soil metabolism study (MRID 47261401) represents the top layer of soil under oxygenated conditions, w ith half-lives of parent tr iclosan and the transformation product methyl triclosan of 2.5-11 and 39-153 days , respectively. In one aerobic soil, methyl triclosan was stable with no apparent degradation. Under anaerobic soil c onditions (top layer of soil after a rain), triclosan was stable (MRID 47261401).

Under aquatic conditions (water and sediment), tr iclosan partitions from the water phase to the sediment phase. The water and total system ha lf-lives in the aerobic aquatic metabolism study (MRID 47261407) were 1.2-1.4 days and 41-58 days, respectively. No significant degradates were formed in the study. However, there was no apparent degradation under aquatic conditions in absence of oxygen (MRID 47261406).

In addition, the Agency has received supplementa l studies for soil nitrif ication (OECD 216) and soil respiration (OECD 217) for triclosan. While the studies are considered to be supplemental information, no additional data are e xpected to be required. These studies indicate that neither soil nitrific ation (MRID 47261403) nor soil re spiration (MRID 47261404) are inhibited at concentrations up to 2 ppm (mg/kg) in soil.

Additional studies on triclosan metabolism in envir onmental compartments were identified in the public literature. There are thr ee public literature st udies cited in Table 16 but these have not been formally reviewed to date. These studies will be reviewed as part of the fate assessment in registration review and acceptable re sults will be use to refine half- life values for use in the risk assessment. All of them provide longer parent triclosan half-lives than the guideline study (MRID 47261401) and one study, Christensen (1994b), also provides additional formation data on methyl triclosan.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 60 of 116 Table 16 - Metabolism of Triclosan with Formation of Degradates

Parameter Half-life of Triclosan (unless specified) Source/ Study Classification/ Comments Aerobic Soil Metabolism (OPPTS 835.4100, 162-1)

Gartenecker loam, 1.73 % OC, Swiss soil

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 Half-lives

2.7 days (parent) 39 days (methyl triclosan)

11 days (parent) Stable (methyl triclosan)

2.5 days (parent) 97 days (methyl triclosan)

3.3 days (stable) 153 days (methyl triclosan) MRID 47261401; Adam, 2007 (Guideline study) Acceptable

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

35, 29, and 17 days in silt loam, loam, and sandy loam soils treated with sewage sludge.

Percent degradation was 77-93 % (average of 83 %) with up to 62-80 % methyl triclosan formation. 14-20 % mineralized to CO 2 Christensen, 1994b Quality unknown, study not formally reviewed.

29-83 days for loamy sand, sandy loam, and sandy soil After 100 days, 21-25, 16-43, and 20-45 % of triclosan remained Cha and Cupples, 2010 Quality unknown, study not formally reviewed.

No degradate analysis Anaerobic Soil Metabolism (835.4200, 162-2) Stable MRID 47261401, Adam, 2007 Acceptable Anaerobic Aquatic Metabolism (OPPTS 835.4300) Stable MRID 47261406, Christensen, 1994a Acceptable

### Docket Number: EPA-HQ-OPP-2012-0811

Page 61 of 116 Parameter Half-life of Triclosan (unless specified) Source/ Study Classification/ Comments 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 MRID 47261407, Adam, 2006 Acceptable

Soil respiration and nitrifica tion No effect of triclosan treatments up to 2 ppm MRIDs 47261403 and 47261404 Supplemental but no additional data expected to be required 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 U.S. soils Quality unknown, study not formally reviewed. High treatment rate



### Ionization of Triclosan and Environmental pHs

Like most compounds with an acid ionizable functional group, triclosan will exist in both an unionized (protonated) and ioni zed (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 fo r triclosan is 8.14 at 20 o 

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

### C is a representative environmental temperature and is relevant for environmental risk assessment. At pH va lues 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 HendersonHasselback Equation (http://chemistry.about.com /od/acidsbase1/a/hende rsonhasselbalch.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 triclo san in soil is expected to be present in the

### Docket Number: EPA-HQ-OPP-2012-0811

Page 62 of 116 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 Agency is aware of two open literature leac hing-adsorption-desorption studies for triclosan. The Agency anticipates reviewing these studies prior to risk assessment.

Table 18 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 environmenta l pH and the degree of non-ionization/ionization of tr iclosan (Thompson and Goyne, 2012). The 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 valu es. Because soil has a negative charge, sorption will decrease as the pH of the soil increases.

Table 18 - Leaching and Adsorption-Desorpt ion of Triclosan to Soil and Sediment

Parameter Value Source/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 Quality unknown, study not formally reviewed. No degradate analysis

Kd values of 33, 55, and 51 ml/g Koc values of 5,613, 6,310, and 3,968 ml/g in loamy sand, sandy loam, and sand soils Cha and Cupples, 2010 Quality unknown, study not formally reviewed No degradate analysis



### Terrestrial Field Dissipation, Leachin g, Runoff, and Crop Uptake (835.6100)

Triclosan has been commonly detected in sewage sludge across the country. As a result triclosan may potentially be applied to agricultural fiel ds as a contaminant of sewage sludge land applications. Triclosan input from EPA registered use patterns is expected to be primarily from

### Docket Number: EPA-HQ-OPP-2012-0811

Page 63 of 116 industrial uses in textile manu facturing and would therefore ha ve limited geographic impact. The geographically-widespread nature of the detections in the environm ent indicates that that while the EPA registered antimicrobial uses may pot entially contribute to the exposure in some localized areas with industrial sources, the pr imary contribution is expected to be from the personal care product uses 15 

### . The Agency is aware of 13 fiel d dissipation studies, one guideline study (Christensen, 1994b) and 12 op en literature studies ; these are listed in Table 19. None of these studies have been reviewed by the Agenc y, but they will be reviewed during the risk assessment phase to determine their usefulness in the risk assessment. Some of the studies appear more than once in the table because th ey contain information on overall environmental fate and not just dissipation.

Table 19 - Terrestrial Field Dissipation, Sur face Runoff, Leaching, and Crop Uptake

Parameter Value Source/Comments 

### Degradation in sewage-sludge amended soils (no guideline number) Half-lives of 39, 29, and 10 days, respectively. 77, 79, and 93 % reduction in triclosan concentrations in silt loam, loam, and sandy loam soils Christensen, 1994b 62-80 % was converted to methyl triclosan and 14-20 % was mineralized Quality unknown, study not formally reviewed. Half-lives of 0.4-12.5 and 0.6-7 days in sandy loam soil Degradation faster in liquidmunicipal biosolids than in dewatered municipal biosolids Al-Rajab et al., 2009 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 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 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 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 but1,000 ppm rate did not reach halflife 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 Quality unknown, study not formally reviewed. Australia Sandy soil

### Docket Number: EPA-HQ-OPP-2012-0811

Page 64 of 116 Parameter Value Source/Comments

Surface runoff fr om treated soil Runoff concentrations of 26 and 258ng/l from injected and surfaceapplied liquid sludge Topp et al., 2008 Quality unknown, study not formally reviewed. Ontario, Canada Silt loam soil with wheat stubble No degradate analysis Leaching through soil filters (activated) 83-140 ng/l flow rate (average of 140 ng/l) with 90 % removal rate 7-30 ng/l flow rate (average of 14 ng/l) with 39 % removal rate Bester and Schafer, 2009 Quality unknown, study not formally reviewed. K d of 160 ml/g Tile drainage concentrations Tr iclosan present in water for 9 months Maximum concentration of 14,000 ng/g in treated soil Maximum concentration of 230 ng/l in tile water. Sewage concentrations of 240-3,680 ng/l in 2005 and 2006 Edwards et al., 2009a Edwards et al., 2009b Quality unknown, study not formally reviewed.

Field dissipation, leaching, and crop uptake Loam, loamy sand, and sandy loam soils in Canada Soils had 0.7-1.4 % OC and pH values of 5.7-6.1. Triclosan reached 74 ng/l in tile drainage, but did not reach ground water at >2 meters of depth. There was no measurable crop uptake in wheat. Gottschall et al., 2012 Quality unknown, study not formally reviewed.

Leaching in sludge-t reated fields (no guideline) Triclosan detected in tile drainage at 150 ng/l from subsurface application Triclosan detected in tile drainage at 3,676 ng/l from surface application Detections occurred immediately after application Macropore flow was primary reason for detections in tiles Lapen et al., 2008 Ontario, Canada 2.1 % OC, Clay loam Quality unknown, study not formally reviewed. No degradate analysis

Soil columns from Mexico Triclosan concentrations in liquid sludge of 84-1,032 ng/l Up to 2.2 % of applied triclosan in leachate (max in sandy loam soil) Gibson et al., 2010 Quality unknown, study not formally reviewed. Soils in Mexico treated with sludge repeatedly for 10-90 years and cropped Textures ranging from sandy loam to clay soils No degradate analysis

### Docket Number: EPA-HQ-OPP-2012-0811

Page 65 of 116 Parameter Value Source/Comments Triclosan applied to 774-949 ug/ha to loamy sand, sandy clay loam, and clay soils in UK.

Most triclosan present in top 10 cm as either parent compound or methyl triclosan (2-8 % triclosan and 27-42 % methyl triclosan).

Triclosan residues present in 10-20 cm of depth as either parent compound or methyl triclosan (2.5-5 % triclosan and 9-18 % methyl triclosan).

3-6.5 % of each compound in 20-30 cm depth

Total recovery of 49-84 % of triclosan and methyl triclosan . Remainder mineralized or sorbed. Butler et al., 2012 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 sorption 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 8.0-8.1for soil and 7.6 for sludge. The preexisting triclosan concentrations were 9.7, 6.3, and 1,401 ng/g or ng/l, respectively. Duran-Alvarez et al., 2012 Quality unknown, study not formally reviewed.



### 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 i ndustrial sources, the ma in contributor is the personal care product uses in most areas without industrial sources 15 

### . Surface water and

15 According to the 2004 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 (Fang et al., 2010).

### Docket Number: EPA-HQ-OPP-2012-0811

Page 66 of 116 sediment exposure most likely result from the effluent from WWTPs which contains small amounts of triclosan relative to th e portion that is sorbed onto se wage sludge. The studies cited below in Table 20 demonstrate that triclosan is typically found in water in the ng/l (parts-pertrillion, ppt) concentration range and in sedi ment in the ng/g (parts-per-billion, ppb) concentration range. There were 17 articles fo r surface water occurrence, five for finished reclaimed wastewater and ground wa ter, and one for bottom sediment. The higher detections in surface water and bottom sediment and the lower con centrations in the landfill leachate and wells are consistent with the fact that triclosan has a limited water sol ubility (12 mg/l) and appears to be strongly sorbed to soils and sediments. Th e Buth (2010) article also contains information on the relative amounts of the chlorinated tric losan transformation products formed in the environment. None of these studies have been formally reviewed, but wi ll be reviewed during Registration Review to determine thei r usefulness in risk assessment.

Table 20 - Environmental Monitoring Studies for Triclosan

Medium Range Unit Average Median No. Samples No. Detections Percent Detection Comments References

Surface Water 0.01-2.3 ng/l 0.19 0.05 85 45 53 Various streams in U.S. Barnes et al., 2002 Quality unknown, study not formally reviewed. USGS

<3-10 ng/l NA NA NA NA NA Ruhr River Catchment in

Germany Bester (2005) Quality unknown, study not formally reviewed.

1.6-29 ng/l 10.9 12.4 29 21 72 Stormwater canals and Bayou St. John in New Orleans Boyd et al, 2004 Quality unknown, study not formally reviewed.

60-80 ng/l 70 70 3 2 66 Denton, TX Coogan et al, 2007 Quality unknown, study not formally reviewed.

0.398-

1.02 ng/l 0.627 NA 2 2 100 Toxicity of triclosan and formation of methyl triclosan

in estuarine

systems DeLorenzo et al, 2008 Quality unknown, study not formally reviewed USGS

4.9-13.7 ng/l 7.5 NA 13.7 13.7 100 Estuarine water in Charleston Harbor Fair et al, 2009 Quality unknown, study not formally reviewed.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 67 of 116 Medium Range Unit Average Median No. Samples No. Detections Percent Detection Comments References

0.021-1 (RL=1) ng/l 0.89 (includes

ND) 1 5 47 10.6 49 locations 18 states and Puerto Rico Unfiltered

samples Focazio et al., 2008 Quality unknown, study not formally reviewed USGS

110-640 ng/l NA 200 and 110 for 1 st and second downstr

eam location

s 10 for each location 6 7 60-70 Downstream of 10 WWTPs Glassmeyer et al., 2005 Quality unknown, study not formally reviewed USGS

2,300(maximum) ng/l 176 50 145 90 62 Streams with minimal dilution Unfiltered water samples Kolpin et al, 2002 Quality unknown, study not formally reviewed USGS

10-4,010 ng/l 193 186 36 36 100 12 WWTP
p lants in Canada

with 1,215- 105,000 m3/day

treated input.

Lagoon, activated sludge,

and activated sludge/ filtration
treatments 35-100 % residential Lishman et al., 2006 Thames River, Canada Quality unknown, study not formally reviewed.

70-650 ng/l NA NA NA NA NA None Poiger et al., 2003 and Linstrom et al., 2002 34-92 % removal Quality unknown, study not formally reviewed. p. 172 of Australia

12 ng/l 12 12 3 1 33 Stream with >90 % treated
wastewater 4 o treatment Vanderford and Snyder, 2006 Quality unknown, study not formally reviewed.

0.4-85

(dry weight) ng/g N/A N/A 24 24 (>0.4 ng/l) 100 Sediment in Minnesota freshwater

bodies 58 % of samples downstream of WWTPs were

greater than

upstream Venkatesan et al., 2010 Quality unknown, study not formally reviewed.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 68 of 116 Medium Range Unit Average Median No. Samples No. Detections Percent Detection Comments References

1-9

26 ng/l

ng/g 3

26 NA 41

12 12 NA Lower Hudson River Estuary Water Sediment Wilson et al, 2009 Quality unknown, study not formally reviewed.

1,130 (maximu m) ng/l NA NA 14 9 64 Baltimore City and County watersheds 9-60 % removal Young et al, 2008 Quality unknown, study not formally reviewed.

193 ng/l NA NA 4 1 25 West Prong Litte River, East Tennessee Yu and Chu, 2009 Quality unknown, study not formally reviewed.

Finished Reclaime d Waste Water

and Ground Water 0.021-1 (RL=1) ng/l 0.89 (includes

ND) 1 47 5 10.6 25 samples in 12 states and Puerto Rico 441 wells sampled Barnes et al., 2008 Quality unknown, study not formally reviewed USGS

<1.0 NA NA NA 5 3 60 Leachate from landfills in GW

in Indiana Buszka et al, 2009 Quality unknown, study not formally reviewed USGS

No detection

s NA NA NA 11 0 0 Compounds in Karst water in Florida Katz and Griffin, 2008 Quality unknown, study not formally reviewed.

280- 2,110 ng/l 1,430 NA 6 3 50 Reclaimed wastewater in

California Loraine and Pettigrove, 2006 Quality unknown, study not formally reviewed.

Bottom Sediment 4-10

13-14 ng/g for tricl

osan 10 (1998) 4 (2008)

13.5 (1998- 2003) 10 (1998) 4 (2008)

13.5 (1998- 2003) 2 2 100 Triclosan Mississippi River sediment in Minnesota

Lake Pepin

sediment triclosan concentrations Buth et al., 2010 Concentrations of 4- chloro triclosan, 6- chloro triclosan, and 4,6-dichloro triclosan 1-80 pg/g for chlorinated derivatives in Mississippi River (most<20) 50-85 pg/g for 2,8- DCDD Up to 4 pg/g for others in Lake Pepin Quality unknown, study not formally reviewed.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 69 of 116 Bioconcentration in Fish (835.1730) and other Aquatic Organisms

Triclosan and its transformation product methyl tr iclosan have been detected in fish, snails, dolphins, and algae in both freshw ater and brackish/salt water (Tab le 21). Acceptable studies for bioconcentration in fish (850.1230) and in oysters (850.1710) are stil l needed because none have been submitted to the Agency; the Agency required these studies as part of the post-RED DCI. Triclosan and methyl triclosan are likely to a ccumulate in aquatic organisms because the log P (log Kow) values are 4.76 and 5.2 (>3, leve l of concern for bioconcentration and bioaccumulation), respectively, and both compounds will need to be addressed in each study. The field monitoring studies in Table 21 will be re viewed to gain any additional information that may be used for risk characterization.

Table 21 – Biological Field Monito ring of Aquatic Organisms

Parameter Value Source/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 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 Netherlands Quality unknown, study not formally reviewed. No degradates analyzed

0.12-0.27 ng/g (mean of 0.18 ng/g) with 31 % detection frequency at Charleston 0.025-0.11 ng/g (mean of 0.072) with 23 % detection in Florida. Influent and effluent concentrations of 2,800-3,400 and 190 ng/l at Charleston, SC. Charleston estuarine concentrations were 4.9-14 ng/l (7.5 ng/l average) Fair et al., 2009 Bottlenose dolphins ( Tursiops
truncatus ) United States Quality unknown, study not formally reviewed.

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 μ g/g ww) Leiker et al., 2008 United States USGS Quality unknown, study not formally reviewed. Methyl triclosan

BCF value of 1.7X 30-day concentration of 461 ng/g dry weight of triclosan in 300 ng/l in Mediterranean mussel ( Mytilus galloprovincialis ) Depuration half-life of 12 days—slower than uptake rates Gatidou et al., 2010 Mediterranean mussel (Mytilus galloprovincialis) Quality unknown, study not formally reviewed. Greece

### Docket Number: EPA-HQ-OPP-2012-0811

Page 70 of 116 Parameter Value Source/Comments

Bioconcentration in snails and algae (no guideline) Triclosan concentrations of 112, 59,000, and 162,000 pptr 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 concen trations of 4.2-365 ng/g lipid in different fish (most <100 ng/g) Coogan and LaPoint, 2008 Quality unknown, study not formally reviewed.

United States Methyl triclosan Dissertation at: http://digital.library.unt.edu/ark:/67531/metadc 3986/m2/1/high_res_d/dissertation.pdf



### Wastewater Treatment (no guideline)

The Agency as part of the post-RED DCI requi red 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 wa s 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 e nvironmental exposure from use at plastic manufacturing facilities and th e field monitoring requirement was dropped. The registrants submitted an acceptable textile monitoring study in response to the post-RED DCI (MRID 48858101). Two textile facili ties were chosen to collect data on the concentrations of triclosan and methyl triclosan present in their effluent wastewaters after triclosan was applied to textiles using the exhaustion proce ss (Table 22). This process uses a jet machine to apply triclosan and other ingredients to textiles at high temperature. At the two f acilities selected the spent or remaining solution from the exhaustion process is discharged to the on-site wastewater treatment plants before the resulting effluent is discharg ed to surface waters. Monitoring specifically at facilities that have their own treatment facilities allows better identification of triclosan 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 de termined that for facility 1, stable operations could possibly be achieved in 2 to 3 weeks follo wing the initiation of the production run. It was further noted that stable effluent concentration of the active attain ed peak concentration in 7 day cyclic fashion consecutively.

For facility 2, which is in used on a regular basi s, the best sample regime was obtained through a 5 consecutive, 24 hour compos ite effluent samples.

In all 22 samples were analyzed for presence and quantification of triclosa n and methyl triclosan for both facilities. The average and maximum tric losan and methyl triclo san concentrations in effluent and in-stream under 7Q10 c onditions are listed in Table 22.

### Docket Number: EPA-HQ-OPP-2012-0811

Page 71 of 116 Table 22 - Textile Monitoring Facility Characteristics Application/ Parameter/ Characteristics Facility # 1 Facility # 2 Comments

Use pattern Intermittently used Constantly used - Amount of triclosan used during study 327 pounds 636 pounds -

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 volume (MG) 2.25 2 EQ Basin for Fac#2 Aeration lagoon MLSS 2500 mg/L a 

### 3.8 MG Aeration lagoon 1 & 2 Clarifier volume (MG) 0.147/operation (2 in operation) 0.021 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: milli on gallons per day; Min: minimum; Max: maximum

Table 23 - Textile Triclosan and Methyl Triclosan Monitoring Concentrations Analyte Average (μg/L) Maximum (μg/L) Triclosan Facility 1 Triclosan Facility 2 Triclosan Facility 1 IWC 0.0032 0.0061 Triclosan Facility 2 IWC 0.0331 0.0432 Methyl triclosan: Facility 1 and Facility 2 <0.0018 <0.0018

IWC: in-stream waste concentra tion (based on NPDES 7Q10 flow).

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Page 72 of 116 

# APPENDIX C: Ecotoxicology Profile

Terrestrial Organisms

Birds

The requirement for acute oral toxicity data for tr iclosan 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 te st 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 co ntaining 3.89% ai was found to be practically nontoxic (northern bobwhite LD 50 

### >2000 mg ai/kg bw/day).

The requirement for subacute dietar y toxicity data for triclosan is satisfied. A subacute dietary study using the TGAI is require d on a case-by-case basis dependi ng on the results of lower-tier ecological studies and pertinent environmental fa te characteristics in order to establish the toxicity of a chemical to avian species. The results of two s ubacute 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 practically 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 24 - 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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 73 of 116 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 Triclosan99.7 % 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 requ ired by the Agency. 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 twogeneration rat reproduction data are available fo r triclosan. Refer to Appendix A, Toxicology Profile, of this document for a description of laboratory mammalia n toxicity data. Information about triclosan’s potential as an endocrine disruptor is also desc ribed in Appendix A.

Based on submitted mammalian data 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 re quired at this time to conduct a risk assessment for mammalian wildlife.

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Page 74 of 116 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 toxi c to freshwater fish and invertebrates, and also has a detrimental impact on reproduction in the part s per billion range (Table 25). One available subchronic sediment toxicity st udy indicates that triclosan does not adversely impact survival, emergence or development rate of freshwater benthic invertebrates (T able 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 tr iclosan toxicity for estuarine/marine fish and a shrimp. Acute data is also lacking for an estuarine/marine mollusk. A study is expected to be required.

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 establ ish the toxicity of triclosan to freshwater fish. The preferred acute test species are rainbow trout ( Oncorhynchus mykiss ) and bluegill sunfish ( Lepomis macrochirus ). Because there is potential for endocrine effects, a fish full life cycle rather than an early life stage is used to establish chroni c reproductive effects from triclosan. Acute toxicity for the species tested in the fish full life cycl e test is used in the calculation of an acceptable acute-t o-chronic ratio (ACR) to extrap olate 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 relationshi p of toxicity with pH is desi rable which means testing of the same species under different pH conditions. Howe ver as an alternative, studies conducted under pH conditions that optimize the unionized state, which is generally considered the more bioavailable and toxic state, woul d be conservatively used to repr esent toxicity at higher more alkaline conditions under which th e ionized form would dominate.

A rainbow trout (cold water species) and a fa thead minnow (warm water species) study with technical grade triclosan were submitted to the Ag ency to support registration (Table 25). Both studies are classified as Supplemental inform ation. 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% duri ng the exposure period which is no t sufficiently stable. From other similar studies triclosan needs frequent replacem ent such as flow-through conditions to ensure stable exposure concentrations. Values based on nominal or av erage measured concentrations potentially underestimate se nsitivity to triclosan.

There are several acute freshwater fish and amphibian studies in the open literature, a preliminary list of public liter ature obtained by the Office of Water and provided to AD is

### Docket Number: EPA-HQ-OPP-2012-0811

Page 75 of 116 provided in Table 26. The Agency has started but not completed the review of these data for use in performing the risk assessment. As discussed in Section 4.4 Effects Anal ysis Plan, a search of the public literature for triclosan effect studies and a review of the rele vant 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 meda ka, a non-native North American species and these results are summarized in Ta ble 25. In the Foran, Bennett, and Benson (2000) study the control results are not reported and without this inform ation the study quality cannot be verified and is therefore Unacceptable at this time. In the other reviewed study, Ishibashi et al (2004), the reported triclosan con centrations were not sufficiently stable (decline >30%) over the renewal period. Acute toxicity values range fo r 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 th is data because of the instabil ity 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 iden tified as conducted under static conditions with no analytical measurements of triclosan concentrations and are therefore not suitable for use in a risk assessment.

Three additional acute studies we re conducted with a triclosan fo rmulation, Issue Plus II, one study with Zebrafish which was found to be Un acceptable and a 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 pr eliminary 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 the review of these data for use in pe rforming the risk assessment. In this case to establish chronic toxicity, a fish full life cycle te st is used to address e ndocrine effect concerns on reproduction.

As discussed in Section 4.4, the Effects Analysis Plan, a search of the public literature for triclosan effect studies and a re view of the relevant studies f ound is planned as part of risk assessment phase of registration review. There are two open literature st udies 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 discounted. No significant effects on se x ratio or on female phenotypic sex characteristics as measured by sexually dimor phic fin shape and size were observed up to the highest concentration tested, 100 ppb (nominal). There was a signi ficant increase in fin size in males at the highest concentra tion tested. Foran, Bennett, an d Benson (2000) concluded that while there was no statistically significant effect on sex ratio there appeared to be a weak trend

### Docket Number: EPA-HQ-OPP-2012-0811

Page 76 of 116 of increasing males with increasing triclosan concentration and taken with the increased male fin length at the highest concentrati on suggested that tric losan could be weakly anti-estrogenic/ androgenic. There are statistical tests that can better ev aluate the existence of a trend than the tests used. The data in the j ournal article are insu fficient 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 medaka by Ishibashi et al . (2204) also showed that triclosan has hi gh toxicity on the early life stages (100% mortality (96-h LC 50 

### 399 ppb, nominal; NOAEC for 156 ppb for hatching success and time-tohatch). When the medaka were exposed to triclosan at 20, 100 and 200 ppb nominal (8.3, 46.4, 112 ppb average measured concentrations, respectiv ely, 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 po tential to induce vitellogenin in male medaka but with no adverse effect on reproduc tive success and offspring (Ishibashi, et. al ., 2004). None of the studies are full life cycle te sts and a fish full life cycle st udy 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. Three acute studies with D. magna using technical triclosan (>98% ai) have been submitted. One of the studies upon re view was classified as unacceptable because measured triclosan concentrations were hi ghly erratic and ther efore actual exposure concentrations 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 tr iclosan 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 triclo san solubility whichever is lower). In the remaining study (MRID 43046002),) measured concentrations s howed triclosan was not stable and while a 48-h EC 50 

### of 390 ppb ai based on nominal concentrati ons 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 assessm ent unless alternative data from th e 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 inve rtebrates. A life cycl e study is expected to be required.

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Page 77 of 116 Table 25 - 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 Triclosanpharmaceutical 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

Japanese medaka ( Oryzias latipes ), <24-hrpost-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

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Page 78 of 116 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-hrold 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

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

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Page 79 of 116 Species % Purity Test Type/ Temp/

pH/ Hardness

or Salinity b Endpoint (ug ai/L) a Toxicity Category Study Classification/ Source/ Comments

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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 80 of 116 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 ), eggcarrying adults of various ages (first offspring were discarded) Pharmaceutical

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 = Static; 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 tests 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 26 - Acute Toxicity of Triclosan to A quatic 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 submitted 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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 81 of 116 Species Method 1 Chemical Purity Endpoint pH Effect Conc. (μg/L) Reference/ Comments Rainbow Trout, Oncorhynchus mykiss 96-h LC 50 350 Ciba 1998**

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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Page 82 of 116 Species Method 1 Chemical Purity Endpoint pH Effect Conc. (μg/L) Reference/ Comments 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 27 - 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 postfertilized 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 than measured

### Docket Number: EPA-HQ-OPP-2012-0811

Page 83 of 116 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 Triclosanpharmaceutical 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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 84 of 116 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 Pharmaceutical

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, doseresponse 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 estuarine/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 28 - Chronic Toxicity of Triclosan to Aquatic Animals from Open Literature Provided by OW

Species Test Type Chemical (% purity) pH Chronic Limits (NOAEC-LOAEC) (μg/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
Northern leopard frog Rana pipiens ELS - 230->230 Growth Fraker and Smith 2004

### Docket Number: EPA-HQ-OPP-2012-0811

Page 85 of 116 Species Test Type Chemical (% purity) pH Chronic Limits (NOAEC-LOAEC) (μg/L) Reference/ Comments
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 29 - Toxicity of Triclosan to Se diment 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/kgsediment (Survival, Emergence Ratio, Development Rate) Supplemental MIRD 475866-01 No growth measurements, no reproduction effect measurements (length/weight) made on the larvae



### Estuarine/Marine Fish and Invertebrates-Triclosan

For triclosan, material preservative uses, an acute toxicity study with an estuarine/marine fish, a mollusk 16 

### , and a shrimp 17 

### and a chronic test with the shrimp using the TGAI are used to establish the toxicity of triclosan to estuarine/marine an imals. To establish a saltwater ACR, the acute shrimp value is divided by its chronic value. No acute or chronic toxicity data have been submitted 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 reviewed as part of the risk assessment phase of registration review. An acu te 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, where acute data for saltwater fish and mysid were missing, values were modeled using Web-ICE (see Appendix D) and ECOSAR as alternative s ources 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 110 ppb for the mysid, Americamysis bahia

.

16 Embryo-larvae or shell deposition

17 Penaeidae or Mysidacea

### Docket Number: EPA-HQ-OPP-2012-0811

Page 86 of 116 Benthic Invertebrates

For triclosan, material preservative uses, sediment toxicity studies are used because triclosan and methyl-triclosan are expected to adsorb to aquatic sediments (K oc 

### = 8417-23,380 ml/g). One chronic study (no guideline no.) has been submitte d for triclosan. No adverse impacts on midge larva emergence or development rate occurred at sediment concentrations up to 100 mg ai/kg parent triclosan. No additional sediment testing is expected to be required.

Aquatic Plants

For triclosan, material preservative uses, testi ng with four nonvascular species (a freshwater diatom 18 

### , a marine diatom 19 

### , a green algae 20 

### , and a cyanobacterium 21 

### ) and one vascular species (duckweed) using TGAI are used to establish toxic ity of triclosan to aqua tic plants. ). The registrant submitted an acceptable duckweed ( L. gibba ) study and three acceptable nonvascular species studies (freshwater diatom, Navicula 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 ( Scenedesmus subspicatus ) data was obtained from open literature Orvos et al. (2002). Collectively these stud ies indicate that nonvascular aq uatic plants, especially green algae (IC 50 

### = 0.7 μg ai/L) and cyanobacteria (IC 50 

### = 1.2 μg ai/L) are highly susceptible to triclosan. Duckweed (IC 50 

### >62.5 μg ai/L) is much less suscep tible than algae. No additional aquatic plant data are expected to be needed for triclosan.

Table 30 - 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

Anabaena flosaquae , 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

18 Navicula pelliculosa
19 Skeletonema costatum
20 Pseudokerscheneria subcapitatum [formerly Selanastrum capricornutum ]
21 Anabaena flos-aquae

### Docket Number: EPA-HQ-OPP-2012-0811

Page 87 of 116 Species % Purity Test Type/ Temp/ pH/ Hard b Endpoint (ug ai/L) Study Classification/ Source/ Comments Lemna gibba
, Duckweed 99.5 S 7-d IC 50 > 62.5 ppb NOEC < 12,5 ppb Acceptable MRID 444228-01



### Table 31 - 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 Analytical grade S, U 3 IC 25 (Growth) - - - 3.4 Tatarazako et al. 2004 Green alga Pseudokirchneriella subcapitata Analytical 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 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 subspicatus ≥ 96.1% S, M 4 IC 50 (growth -biomass) 7.5- 7.8 - - 0.7 Orvos et al. 2002 Green alga Scenedesmus subspicatus ≥ 96.1% S, M 4 Growth –biomass 7.5- 7.8 0.5 1.2 Orvos et al. 2002 Green alga Scenedesmus subspicatus ≥ 96.1% S, M 4 IC 50 (growth -biomass) 7.5- 7.8 - - 1.4 Orvos et al. 2002

### Docket Number: EPA-HQ-OPP-2012-0811

Page 88 of 116 Species Purity Method
1 Study Duration

(days) Effect Measured pH NOEC (μg/L) LOEC (μg/L) ICx (μg/L) Reference

Green alga Scenedesmus subspicatus ≥ 96.1% S, M 4 Growth –biomass 7.5- 7.8 0.69 1.5 Orvos et al. 2002 Green alga Scenedesmus subspicatus ≥ 96.1% S, M 3 IC 50 (growth rate) 7.5- 7.8 - - 2.8 Orvos et al. 2002 Green alga Scenedesmus subspicatus ≥ 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



### Table 32 - Other Chronic Data on the Effect s of Triclosan on Aquatic Organisms from Open Literature Reviewed by OW

S pecies 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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 89 of 116 S pecies Purity Duration Effect Measured pH NOEC (μg/L) LOEC (μg/L) MATC (μg/L) Reference/ Comments 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 subspicatus - 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
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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 90 of 116 S pecies Purity Duration Effect Measured pH NOEC (μg/L) LOEC (μg/L) MATC (μg/L) Reference/ Comments 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
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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 91 of 116 S pecies Purity Duration Effect Measured pH NOEC (μg/L) LOEC (μg/L) MATC (μg/L) Reference/ Comments 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 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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 92 of 116 S pecies Purity Duration Effect Measured pH NOEC (μg/L) LOEC (μg/L) MATC (μg/L) Reference/ Comments 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

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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 93 of 116 Aquatic Organisms - Methyl Triclosan

For methyl triclosan, a potential reaction product under certain envi ronmental conditions, there is a lack of ecological toxicity da ta. There is one aquatic plant study for methyl-triclosan and it shows methyl triclosan as being le ss toxic to algae than the 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 im mobilization was observed at test concentrations less than or equal to 55 μg ai/L; one of 20 daphni ds was reported to be immobile at the end of the 48-h te st at 180 μg ai/L. No chronic da ta are available. No methyl triclosan was detected in effluent from textil e manufacturing and is ther efore not considered a concern for the uses being assessed. Monitoring de monstrated 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 no additional da ta are expected to be required.

Table 33 - 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

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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 94 of 116 REFERENCES—ECOTOXICOLOGY DATA

Adolfsson-Erici, M., M. Pettersson, J. Par kkonen and J. Sturve. 2002. Triclosan, a commonly used bactericide found in human milk and in the aquatic environment in Sweden. Chemosphere 46(9-10): 1485-1489.

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 transf ormation product of the bactericide triclosan, in fish from various lakes in Switzer land. Environ. Sci. Technol. 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 tr eatment 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 al ong a hydrological, biogeochemical, and land use gradient: A holistic watershed appro ach. 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. stream s, 1999-2000. U.S. Geological Survey Open-File Report 02-94.

Bätscher, R. 2006a. Methyl-tri closan: Acute toxicity to Daphnia magna in a 48-hour immobilization test. RCC Ltd. Environmental Chemistry & Pharmanalytics, Itlingen, Switzerland. Study Number A34931.

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Bester, K. 2005. Fate of triclosan and triclosan- methyl in sewage treatment plants and surface waters. Arch. Environ. Contam. Toxicol. 49(1): 9-17.

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Page 95 of 116 Binelli, A., D. Cogni, M. Parolini, C. Riva a nd A. Provini. 2009a. In vivo experiments for the evaluation of genotoxic and cytotoxic effects of triclosan in zebra mussel hemocytes. Aquat. Toxicol. 91(3): 238-244.

Binelli, A., D. Cogni, M. Parolini, C. Riva and A. Provini. 2009b. Cytotoxic and genotoxic effects of in vitro exposure to tric losan and trimethoprim on zebra mussel ( Dreissena polymorpha ) hemocytes. Comp. Biochem. Physiol. C. 150(1): 50-56.

Boyd, G.R., H. Reemtsma, D.A. Grimm and S. Mitra. 2003. Pharmaceuticals and personal care products (PPCPs) in surface and treated waters of Louisiana, USA and Ontario, Canada. Sci. Total Environ. 311(1-3): 135-149.

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(1-3): 137-148.

Borgmann, U., D.T. Bennie, A.L. Ball and V. Pa labrica. 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. Maquieira. 2008. Selective enzyme-linked immunosorbent assay for triclosa n. Application to wastewater treatment plant effluents. Environ. Sci. Technol: 42: 1665-1672.

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 acti on on non target organisms. Comp. Bioch. Physiol. Part C: 145: 464-472.

Capdevielle M., R. Van Egmond, M. Whelan, D. Versteeg, M. Hofmann-Kamensky, J. Inauen, V. Cunningham and D. Woltering. 2008. Considerat ion of exposure and species sensitivity of triclosan in the freshwater environment. Integ. Environ. Assess. Mgmt: 4(1): 15-23.

Chalew, T.E.A. and R.U. Halden. 2009. Environmen tal exposure of aquatic and terrestrial biota to triclosan and triclocarban. J. Am . Water Resour. Assoc. 45(1): 4-13.

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 co ntaining small molecules in personal care products. Toxicol. Appl. Pharm. 221: 278-284.

Ciba. 1998. Irgasan DP 300/Irgacare MP. Toxicol ogical and ecological data. Ciba official registrations 2521. Ciba Specialty Chemicals Inc.

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Page 96 of 116 Ciniglia, C., C. Cascone, R.L. Giudice, G. Pint o and A. Pollio. 2005. Application of methods for assessing the geno- and cyto toxicity of triclosan to C. ehrenbergii . J. Hazard. Materials.
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Coogan, M.A. and T.W. LaPoint. 2008. Snail bi oaccumulation of triclocarban, triclosan, and methyl-triclosan in a North Texas, USA, st ream affected by wastew ater treatment plant runoff. Environ. Toxicol. Chem. 27(8): 1788-1793.

Coogan, M.A., R.E. Edziyie, T.W. LaPoint and B.J. Venables. 2007. Algal bioaccumulation of triclocarban, triclosan, and met hyl-triclosan in a North Texa s 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 e nvironmentally relevant concentrations of the pharmaceutical Triclosan in the marine mussel Perna perna (Linnaeus, 1758). Environ. Pollut. 168: 145-150.

Cuderman, P. and E. Heath. 2007. Determination of UV filters and antimicrobial agents in environmental water samples. An al. Bioanal. Chem. 387(4): 1343-1350.

DeLorenzo, M. E. and J. Fleming. 2008. Indi vidual and mixture effects of selected pharmaceuticals and personal care products on the marine phytoplankton species Dunaliella tertiolecta . Arch. Environ. Contam. Toxicol. 54(2): 203-210.

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 antimicrobi al compound triclosan and formation of the metabolite methyl-triclosan in estuarine systems. Environ. Toxicol. 23(2): 224-232.

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): 425-432.

European Centre for Ecotoxicology and Toxico logy of Chemicals (ECETOC). 2007. Intelligent testing strategies in ecotoxi cology: Mode of action appr oach for specifically acting chemicals. 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 pl asma of wild Atlantic bottlenose dolphins ( Tursiops truncatus ) and in their environment. Environ. Pollut. 157(8-9): 2248-2254.

Fang, J-L., R.L. Stingley, F.A. Beland, W. Ha rrouk, D.L. Lumpkins, and P. Howard. 2010. Occurrence, Efficacy, Metabolism, and Toxicity of Triclosan. Journal of Environmental Science and Health, Part C: Environmenta l Carcinogenesis and Ecotoxicology Reviews

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Page 97 of 116 28(3):147-171. DOI: 10.1080/10590501.2010.504978. http://www.tandfonline.com/doi/pdf/10.1080/10590501.2010.504978

Faust, M., R. Altenburger, T. Backhaus, H. Blan ck, W. Boedeker, P. Gramatica, V. Hamer, M. Scholze, M. Vighi and L.H. Grimme. 2001. Predicting the joint toxicity of multicomponent s -triazine muxtures at low-effect concen trations of individua l toxicants. Aquat. Toxicol. 56:13-32.

Federle, T.W., S.K. Kaiser and B.A. Nuck. 2002. Fate and effects of triclosan in activated sludge. Environ. Toxicol. Chem. 21(7): 1330-1337.

Ferarri, B., N. Paxeus, G. Pinto, A. Pollio, R. Andreozzi, R. Marotta, D. Vogna, G. Lyberatos and J. Garric. 2002. Fate and effect of triclosa n in the aquatic ecosystems: Data for a risk assessment [poster]. In: Society of Envi ronmental Toxicology and Chemistry Annual Meeting in Europe; 2002May 12-16; Vienna, Austria. Brussels (BE): SETAC Europe.
Poster 73-04.

Flaherty C.M. and S.I. Dodson. 2005. Effects of pharmaceuticals on Daphnia survival, growth, and reproduction. Chemosphere. 61: 200-207.

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: 201-216.

Foran, C.M., E.R. Bennett and W.H. Benson. 2000. Developmental evaluation of a potential non-steroidal estrogen: triclosa n. Mar. Environ. Res. 50: 153-156.

Fraker, S.L. and G.R. Smith. 2004. Direct and interactive eff ects of ecologically relevant concentrations of organic wastewater contaminants on Rana pipiens tadpoles. Environ. Toxicol. 19(3): 250-256.

Fort, D.J., R.L. Rogers, J.W. Gorsuch, L. Nava rro, R. Peter and J.R. Plautz. 2010. Triclosan and anuran metamorphosis: No effect on thyroid-mediated metamorphosis in Xenopus laevis

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Franz, S., R. Altenburger, H. Heilmeier and M. Schmitt-Jansen. 2008. What contributes to the sensitivity of microalgae to triclo san? Aquat. Toxicol. 90(2): 102-108.

Fulton, B.A., R.A. Brain, S. Usenko, J.A. Bac k, R.S. King and B.W. Brooks. 2009. Influence of nitrogen and phosphorus con centrations and ratios on Lemna gibba growth responses to triclosan in laboratory and stream mesocosm experiments. Environ. Toxicol. Chem. 28(12):
2610-2621.

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Page 98 of 116 Giddings, J.M. 2007. Review of Proposed Plant- Based Acetochlor Class 2 Water Quality Standards for Minnesota. Complia nce Services International.

Glassmeyer, S.T., E.T. Furlong, D.W. Kolpin, J.D. Cahill, S.D. Zaugg, S.L. Werner, M.T. Meyer and D.D. Kryak. 2005. Transport of chemical and microbial compounds from known wastewater discharges: Potent ial for use as indicators of human fecal contamination. Environ. Sci. Tech. 39(14): 5157-5169.

Gomez, M.J., M.J. Martinez Bueno, S. Lacorte, A.R. Fernandez-Alba and A. Agueera. 2007. Pilot survey monitoring pharmaceuticals and re lated compounds in a sewage treatment plant located on the Mediterranean coast. Chemosphere 66(6): 993-1002.

Greyshock, A.E. and P.J. Vikesland. 2006. Triclosa n reactivity in chloraminated waters. Environ. Sci. Tech. 40(8): 2615-2622.

Haggard, B.E., J.M. Galloway, W.R. Green a nd M.T. Meyer. 2006. Pharmaceuticals and other organic chemicals in selected North-Centra l and Northwestern Arkansas streams. J. Environ. Qual. 35(4): 1078-1087.

Halden, R.U. and D.H. Paull. 2005. Co-occurrence of triclocarban and triclosan in U.S. water resources. Environ. Sci. Tech. 39(6): 1420-1426.

Harada, A., K. Komori, N. Nakada, K. Kitamu ra and Y. Suzuki. 2008. Biological effects of PPCPs on aquatic lives and evaluation of rive r waters affected by different wastewater treatment levels. Wat. Sci. Tech. 58(8): 1541-1546.

Heidler J. and R.U. Halden. 2007. Mass balan ce assessment of triclosan removal during conventional sewage treatment. Chemosphere. 66: 362-369.

Heilman, K.E. 2008. Sublethal effects of triclosan on Potamogeton perfoliatus and Elodea canadensis . M.S. Thesis, Hood College, Frederick, MD. 57 p.

Hua, W., E.R. Bennett and R.J. Letcher. 2005. Tr iclosan in waste and surface waters from the upper Detroit River by liquid chromatogr aphy-electrospray-tandem quadrupole mass spectrometry. Environ. Int. 31: 621-630.

Ishibashi, H., N. Matsumura, M. Hirano, M. Mats uoka, H. Shiratsuchi, Y. Ishibashi, Y. Takao and K. Arizono. 2004. Effects of triclosan on the early life stages and reproduction of medaka Oryzias latipes and induction of hepatic vitelloge nin. Aquat. Toxicol. 67: 167-179.

Kasprzyk-Hordern, B., R.M. Dinsdale and A.J. Guwy. 2009. The removal of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs during wastewater treatment and its impact on the quality of r eceiving waters. Water Res. 43: 363-380.

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Page 99 of 116 Kim, J.W., H. Ishibashi, R. Yamauchi, N. Ic hikawa, Y. Takao, M. Hirano, M. Koga and K. Arizono. 2009. Acute toxicity of pharmaceutical and personal care products on freshwater crustacean ( Thamnocephalus platyurus ) and fish ( Oryzias latipes ). J. Toxicol. Sci. 34(2): 227-32.

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Kobayashi, N., S. Masunaga and J. Nakanish i. 2003. Source identificat ion and behavior of PCDD/Fs and dioxin-like PCBs in Japanese rive r water. J. Jap. Soc. Wat. Environ. 26(1):
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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): 119-130.

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Latch, D.E., J.L. Packer, B.L. Stender, J. VanOverbeke, W.A. Arnold and K. McNeill. 2005. Aqueous photochemistry of triclosan: formation of 2,4-dichlorophenol, 2,8- dichlorodibenzo-p-dioxin, and oligomeriza tion products. Environ. Toxicol. Chem. 24(3):
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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 triclo carban on the structure and function of river biofilm communiti es. Sci. Total Environ. 407(10): 3307-16.

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Leiker, T.J., S.R. Abney, S.L. Goodbred a nd M.R. Rosen. 2009. Identification of methyl triclosan and halogenated an alogues in male common carp ( Cyprinus carpio ) from Las Vegas Bay and semipermeable membrane devices from Las Vegas Wash, Nevada. Sci. Total Environ. 407(6): 2102-14.

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Page 100 of 116 Loraine G.A. and M.E. Pettigrove. 2006. S easonal variations in concentrations of pharmaceuticals and personal care products in dr inking water and reclaimed wastewater in southern California. Envi ron. Sci. Technol. 40: 687-695.

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Page 101 of 116 Miyoshi, N., T. Kawano, M. Tana ka, T. Kadano, T. Kosaka, M. Kunimoto, T. Takahashi and H. Hosoya. 2003. Use of paramecium species in bioassays for environmental risk management: Determination of IC 50 

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Page 102 of 116 OW/ORD Emerging Contaminants Workgroup. 2008b. A quatic life criteria for contaminants of emerging concern. Part II. Illustration of recommendations using data for 17 α

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Page 103 of 116 Singer, H., S. Muller, C. Tixier and L. Pillonel. 2002. Triclosan: occurrence and fate of a widely used biocide in the aquatic environment: fi eld measurements in wastewater treatment plants, surface waters, and lake sediments. Environ. Sci. Tech. 36(23): 4998-5004.

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### Docket Number: EPA-HQ-OPP-2012-0811

Page 104 of 116 Tatarazako N., H. Ishibashi, K. Teshima, K. Kishi and K Arizono. 2004. Effects of triclosan on various aquatic organism s. Environ. Sci. 11:133-140.

Thompson, A. and K. Goyne. 2012. Introduction to the Sorption of Chemical Constituents in Soils. Nature Education Knowledge 3(10):7. http://www.nature.com/scitable/knowledge /library/introduc tion-to-the-sorption-ofchemical-constituents-94841002

Tixier, C., H.P. Singer, S. Canonica and S.R. Mu eller. 2002. Phototransformation of triclosan in surface waters: A relevant elimin ation process for this widely used biocide - laboratory studies, field measurements, and mode ling. Environ. Sci. Tech. 36(16): 3482-3489.

Topp, E., S. C. Monteiro, A. Beck, B. B. Coelho, A.B.A. Boxall, P.W. Duenk, S. Kleywegt, D.R. Lapen, M. Payne, L. Sabourin, H. Li and C.D. Metcalfe. 2008. Runoff of pharmaceuticals and personal care products following app lication of biosolids to an agricultural field. Sci. Total Environ. doi: 10.1016/jscitotenv.2008.02.011.

Toropov, A.A. and E. Benfenati. 2006. QSAR models for Daphnia toxicity of pesticides based on combinations of topological parameters of molecular structures. Bioorgan. Med. Chem. 14(8): 2779-2788.

U.S. EPA. 1983b. Water quality standards regu lation. Federal Register 48:51400. November 8.

U.S. EPA. 1986. Chapter 1-Stream design flow for steady-state modeling. In: Book VI-Design conditions. In: Technical guidance manual for pe rforming waste load allocation. Office of Water, Washington, DC. August.

U.S. EPA. 1987. Permit writers guide to water quality-based permitting for toxic pollutants. EPA-440/4-87-005. Office of Wa ter, Washington, DC.

U.S. EPA. 1991. Technical support document fo r water quality-based toxics control.

EPA-505/2-90-001. Office of Water, Washi ngton, DC, March; or PB91-127415, National Technical Information Service, Springfield, VA.

U.S. EPA. 1994. Water Quality Standards Handbook. 2 nd 

### Ed. EPA-823-B-94-005b. Office of Water, Washington, D.C.

U.S. EPA Science Advisory Board (SAB). 2008. SAB advisory on aquatic life water quality criteria for contaminants of emerging con cern. EPA-SAB-09-007. Ecological Processes and Effects Committee, Science Advisory Board, U.S. EPA. Washington, D.C. [Available

at: http://yosemite.epa.gov/sab/SABPRO DUCT.NSF/b5d8a1ce9b0 7293485257375007012b7/E37 FB6980DCDD9B585257532005F6F2C/$File/EPA-SAB-09-007-unsigned.pdf ].

### Docket Number: EPA-HQ-OPP-2012-0811

Page 105 of 116 U.S. EPA. 1998. Guidelines for ecological risk assessment. EPA/630/R-95/002F. Federal Register 63(93):26846-26924.

U.S. EPA. 2010. Technical support document for th e development of aqua tic life criteria for contaminants of emerging concern. Draft.

U.S. Geological Survey. 2005. Effects of nonpoint and selected point contaminant sources on stream-water quality and rela tions to land use in Johnson County, Northeastern Kansas, October 2002 through June 2004. Scientif ic Investigati ons Report 2005-5144.

Valters, K., H. Li, M. Alaee, I. D'Sa, G. Marsh, A. Bergman and R.J. Letcher. 2005. Polybrominated diphenyl ethers and hydroxyl ated and methoxylated brominated and chlorinated analogues in the plasma of fish from the Detroit River. Environ. Sci. Tech. 39(15): 5612-5619.

van Wezel, A.P. and T. Jager. 2002. Comparis on of two screening level risk assessment approaches for six disinfectants and pharmaceuticals. Chemosphere 47(10): 1113-1128.

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Weigel, S., U. Berger, E. Jensen, R. Ka llenborn, H. Thoresen and H. Huhnerfuss. 2004. Determination of selected pharmaceuticals a nd caffeine in sewage and seawater from Tromso/Norway with emphasis on ibuprofen and its metabolites. Chemosphere 56(6): 583-
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Wilkison, D.H., D.J. Armstrong, S.D. Zaugg a nd D.W. Blevins. 2000. Use of wastewater indicators to assess the impacts of combined sewer overflows on two urban streams. National Groundwater Association Emergi ng Issues Conference, June 7-8, 2000, Minneapolis, MN.

Wilson, B.A., V. H. Smith, F. DeNoyelles and C.K. Larive. 2003. Effects of three pharmaceutical and personal care products on natural freshwater algal assemblages. Environ. Sci. Technol. 37:1713-1719.

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Page 106 of 116 Wind, T. 2004. Prognosis of environmental concen trations by geo-referenced and generic models: A comparison of GREAT-ER and EUSES exposure simulations for some consumer-product ingredients in the Itter. Chemosphere 54(8): 1145-1153.

Wu, J.L., N.P. Lam, D. Martens, A. Kettrup a nd Z. Cai. 2007. Triclosan determination in water related to wastewater treatment. Talanta 72: 1650-1654.

Xie, Z., R. Ebinghaus, G. Floser, A. Caba and W. Ruck. 2008. Occurrence and distribution of triclosan in the German Bight (North Sea). Environ. Pollut. 156(3): 1190-1195.

Yang, L.H., G.G Ying, H.C. Su, J.L. Stauber, M.S. Adams and M.T. Binet. 2008. Growthinhibiting effects of 12 antibacterial agents a nd their mixtures on the freshwater microalga Pseudokirchneriella subcapitata . Environ. Toxicol. Chem. 27(5): 1201-1208.

Ying, G. and R.S. Kookana. 2007. Triclosan in wastewaters and biosolids from Australian wastewater treatment plants. Environ. Intl. 33: 199-205.

Yang, B., G.G. Ying, J.L. Zhao, L.J. Zhang, Y. X. Fang and L.D. Nghiem. 2011. Oxidation of triclosan by ferrate: Reaction ki netics, products identification and toxicity evaluation. J. Haz. Mat. 186: 227-235.

Zhang, S., Q. Zhang, S. Darisaw, O. Ehie a nd G. Wang. 2007. Simultaneous quantification of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and pharmaceuticals and personal care products (PPC Ps) in Mississippi ri ver water, in New Orleans, Louisiana, USA. Chemosphere 66: 1057-1069.

Zhao, J., G. Ying, L. Wang, J. Yang, X. Yang, L. Yang and X. Li. 2009. Determination of phenolic endocrine disrupting chemicals and ac idic pharmaceuticals in surface water of the Pearl Rivers in South China by gas chro matography—negative chemical ionization—mass spectrometry. Sci. Total Environ. 407: 962-974.

Zhao, J., G. Ying, Y. Liu, F. Chen, J. Yang and L. Wang. 2010. Occurrence a nd risks of triclosan and triclocarban in the Pearl River system, South China: From source to the receiving environment. J. Hazard. Mater. doi:10.1016/j.jhazmat.2010.02.082.

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Page 107 of 116 

# APPENDIX D: Web-ICE and ECOSAR Results

Saltwater Fish and Shrimp Predicted Values

The utility of ECOSAR v1.11 for predicting triclo san effect endpoints for saltwater fish and shrimp was checked by examining its success at pr edicting 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 act ual data (ECOSAR 96-h LC 50 

### for fish = 476 ppb versus 260 ppb for fathead minnow; ECOSAR 48-hr EC 50 

### for daphnid = 469 ppb versus 390 ppb (which is an underestimate of t oxicity) for actual Daphnia magna data), so in this case the ECOSAR model appears to underestimate triclosan toxicity to aquatic organisms. Ther efore predictions 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 rainbow trout for triclosan was checked by predicting the fathead minnow value using the rainbow trout. This species model re sulted in a fathead minnow value ((95% lower confidence limit, mean) 514.8, 714.8) which underesti mates 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 underestimat e toxicity, therefore the fath ead minnow value was used to predict a value for saltwater fish.

There are only four chemical 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 provi ded 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) Wat Sol: 23.45 (mg/L, EPISuite WSKowwin v1.43 Estimate)

### Docket Number: EPA-HQ-OPP-2012-0811

Page 108 of 116 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 Class-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 Algae 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.

Phenols:

------- 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:

--------------------------------- Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50)

### Docket Number: EPA-HQ-OPP-2012-0811

Page 109 of 116 Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)



### Web-ICE

Surrogate Species Predicted Species Predicted Values Actual Value Acute 95% LL Rainbow trout (288 ppb) Fathead minnow 714.8 514.8 260 Fathead minnow (260 ppb) Rainbow trout 141 97 288 Fathead minnow (260 ppb) Bluegill sunfish 188 121 370 Ceriodaphnia dubia (235 ppb) Daphnia magna 143 17

Surrogate Species: Rainbow trout ( Oncorhynchus mykiss ) Predicted Species: Fathead minnow ( Pimephales promelas )

Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

288

μ g/L (2.45) 714.82 μ g/L (2.85)

Select Confidence Interval: Lower Limit Upper Limit

95% 514.86 μ g/L 992.45 μ g/L

Model Information Intercept: 0.669768 Slope: 0.888200 Degrees of Freedom (N-2): 79

R 2 : 0.825954 p-value: 0.000000 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

### Docket Number: EPA-HQ-OPP-2012-0811

Page 110 of 116 Surrogate Species: Fathead minnow (Pimephales promelas) Predicted Species: Bluegill (Lepomis macrochirus) Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

260



### μ g/L (2.41) 188.76 μ g/L (2.27)

Select Confidence Interval: Lower Limit Upper Limit

95% 

### 121.54 μ g/L 293.17 μ g/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)

### Docket Number: EPA-HQ-OPP-2012-0811

Page 111 of 116 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

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

μ g/L (2.41) 715.97 μ g/L (2.85)

Select Confidence Interval: Lower Limit Upper Limit

95% 256.71
μ g/L 1996.82 μ g/L

Model Information Intercept: 1.62 Slope: 0.507579 Degrees of Freedom (N-2): 12

### Docket Number: EPA-HQ-OPP-2012-0811

Page 112 of 116 R 2 : 0.536675 p-value: 0.002883 Average value of surrogate (l og 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

Surrogate Species: Daphnid (Ceriodaphnia dubia) Predicted Species: Mysid (Americamysis bahia) Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

235

μ g/L (2.37) 172.48 μ g/L (2.23)

Select Confidence Interval : Lower Limit Upper Limit

95% 3.70 μ g/L 8031.21 μ g/L

Model Information Intercept: 0.090613

### Docket Number: EPA-HQ-OPP-2012-0811

Page 113 of 116 Slope: 0.905133 Degrees of Freedom (N-2): 2

R 2 : 0.964719 p-value: 0.017798 Average value of surrogate (l og 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



### Surrogate Species: Daphnid (Daphnia magna) Predicted Species: Mysid (Americamysis bahia)
Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

260

μ g/L (2.41) 109.65 μ g/L (2.04)

Select Confidence Interval: Lower Limit Upper Limit

95% 77.17 μ g/L 155.80 μ g/L

Model Information
Intercept: 0.087748
Slope: 0.808413
Degrees of Freedom (N-2): 135

### Docket Number: EPA-HQ-OPP-2012-0811

Page 114 of 116 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 115 of 116

# APPENDIX E: For Ecological AssessmentDioxins of Concern and Equivalency Factors

The term “dioxins” is used to represent polychlorinated dibenzo- p -dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Ther e are 210 different congeners of dioxins (75 PCDDs and 135 PCDFs); however, only 17 congener s are considered to be of toxicological concern (listed in Table 34). For these 17 congeners , evidence is sufficient to conclude that a common mechanism of action, i nvolving binding of the chemical s 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 fr om triclosanare 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 congene rs are not among the 17 ( listed below) that are of toxicological concern for mammals, birds, and fish.

Table 34 - Dioxin Congeners of Toxicological Concern; Toxicity equivalency factors for mammals, birds and fish a ssociated 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 = Tetrachlorodibenzofuran; PeCDF = Pentachlorodibenzofuran; HxCDF = Hexachlorodibenzofuran; HpCDF = Heptachlorodibenzofuran; OCDF = octachlorodibenzofuran

### Docket Number: EPA-HQ-OPP-2012-0811

Page 116 of 116 Research has been conducted to characterize th e toxicities of PCDDs and PCDFs especially relative to each other, since these compounds are often pres ent together in the environment. Demonstrated toxic effects of 2,3,7,8-TCDD and other similar-acting PCDD, PCDF and PCB congeners in fish, birds, a nd mammals include adverse eff ects on reproduction, development, and endocrine functions; wasting syndrome; i mmunotoxicity; and mortality in both laboratory and field settings (U.S. EPA 2008b). The EP A (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 to mammals, to birds and to fish (Table 34). In the TEF approach, the toxicities of i ndividual 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 St ockholm Convention as Persistent Organic Pollutants (POPs). These chemicals are persiste nt, 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. Th e toxicity of 2,3,7,8-TCDD is expressed in units of ng/kg-bw, which indicates that this chemical is or ders of magnitude more toxic than pesticides which are typically assessed by OPP. When usi ng the 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, calcu lation of total TEQ is not required, as the congeners formed are not of toxicological concern.