Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 2 of 68 2-(Thiocyanomethylthio)-benzothiazole (TCMTB) Registration Review Team

Antimicrobials Division

Human Health & Environmental Effects Timothy Dole LT Jonathan Leshin William Erickson Siroos Mostaghimi Najm Shamim

Risk Management Sandra OSNeill Karen Leavy Rose Kyprianou

Environment Fate & Effects Division James Lin Christine Hartless

Health Effects Division Donna Davis Sheila Piper Thomas Bloem Mohsen Sahafeyan Yung Yang Bridgett Bobowiec Don Wilbur

Pesticide Re-evalu ation Division Steven Snyderman Avivah Jakob

Office of General Counsel Philip RossDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 3 of 68 TERMS, ABBREVIATIONS AND SYMBOLS

AD Antimicrobials Division A.I. or a.i. active ingredient aPAD acute population adjusted dose ASRI activated sludge respiration inhibition
atm-m 3 /mole atmospheric pressure-cubic meter per mole BCF bioconcentration factor BTOL 2-benzothiazolol BTSA benzothiazol sulfonic acid °C degrees Celsius CaSO 4 calcium sulfate CaSO 3 calcium sulfite CAS Chemical Abstracts Service CFR Code of Federal Regulations CHO Chinese hamster ovary CMA Chemical Manufacturers Association CO 2 carbon dioxide COC concentration-of-concern cPAD chronic population adjusted dose DBB 2,2S-(dithiosbis) benzothiazole DCI data call-in EC 50 median (or 50 percent) effect concentration EC 05 5 percent effect concentration ECOTOX ECOTOXicology EDI estimated daily intake EDSP Endocrine Disruptor Screening Program E-FAST Exposure and Fate Assessment Screening Tool EPI Suite Estimation Program Interface Suite EPA Environmental Protection Agency FDA Food and Drug Administration FFDCA Federal Food, Dr ug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FWP Final Work Plan g/mol grams per mole GLN guideline number HPV high production volume IDS Incident Data System Koc organic carbon normalized soil-water partition coefficient Kd soil-water partition coefficient Kow octanol-water partition coefficient LC 50 median (or 50 percent) lethal concentration LD 50 median (or 50 percent) lethal dose LOAEC lowest-observed-adverse-effect-concentration LOEC lowest-observed-effect-concentration LOAEL lowest-observed-adverse-effect-level Log K ow logarithm of the octanol-water partition coefficient MB 2-mercaptobenzthiazole μg microgramDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 4 of 68 ml/g milliliter per gram mg/kg milligram per kilogram mg/kg/day milligram per kilogram per day mg/L milligram per liter mm Hg millimeter of mercury MOE margin of exposure MRID Master Record Identification Number MRL maximum residue limit N/A not applicable
nm nanometers NOAEC no-observed-adverse-effect-concentration NOAEL no-observed-adverse-effect-level OCSPP Office of Chemical Safety and Pollution Prevention OECD Organization for Economic Co-operation and Development OPP Office of Pesticide Programs PAD population adjusted dose PAI pure active ingredient PDM Probabilistic Dilution Model % percent PC Code Pesticide Chemical Code PCF pounds per cubic foot pH power of hydrogen or power of the concentration of the hydrogen ion PHED Pesticide HandlerSs Exposure Data PIS primary irritation score pKa power of the acid dissociation constant or negative base-10 logarithm of the acid dissociation constant of a solution ppb parts per billion ppm parts per million PWP Preliminary Work Plan QSAR quantitative structure-activity relationship RED Reregistration Eligibility Decision SAR structure activity relationship SF safety factor SSTS Section Seven Tracking System TCMTB 2-thiocyanomethylthio)-benzothiazole TEP typical end-use product TGAI technical grade active ingredient TMDL total maximum daily loads UF uncertainty factor UV/VIS ultraviolet/visible light absorption % w/w percent weight per weight. WP wettable powder WWTPs wastewater treatment plantsDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 5 of 68 

### Table of Contents
1 Introduction .................................................................................................................. ........... 7 1.1 Statutory and Regulatory Authority ................................................................................. 7 1.2 Updates to the Work Plan ................................................................................................. 7 1.3 Case Overview ............................................................................................................... 1 0 1.4 Chemical Identification and Properties .......................................................................... 10 1.5 Use/Usage Description ................................................................................................... 11 1.5.1 Registrations ........................................................................................................... 11 1.5.2 Summary of Regist ered Uses .................................................................................. 12 1.5.3 Usage Information .................................................................................................. 14 1.6 Regulatory History ......................................................................................................... 14 1.6.1 Tolerance Information ............................................................................................ 14 1.7 Incidents ..................................................................................................................... .... 15 1.7.1 Human Health ......................................................................................................... 15 1.7.2 Ecological ............................................................................................................... 16 2 Anticipated Data Needs ........................................................................................................ 16 3 Human Health Risk Assessment ........................................................................................... 21 3.1 Toxicological Endpoints ................................................................................................ 21 3.2 Dietary Exposure ............................................................................................................ 2 2 3.2.1 Residue Chemistry (Agricultural Uses Only) ......................................................... 23 3.2.2 Antimicrobial Uses ................................................................................................. 24 3.2.3 Agricultural Uses, Food and Drinking Water ......................................................... 24 3.3 Occupational and Residential Exposures ....................................................................... 25 3.3.1 Occupational Handler Exposure ............................................................................. 25 3.3.2 Residential Handler Exposures ............................................................................... 27 3.3.3 Residential Post-Applic ation Exposures ................................................................. 27 3.4 Aggregate and Cumulative Exposure ............................................................................. 28 3.4.1 Aggregate Exposures .............................................................................................. 28 3.4.2 Cumulative Exposures ............................................................................................ 28 4 Environmental Risk Assessment........................................................................................... 29 4.1 Environmental Fate Assessment ......................................................................................... 29 4.1.1 Leaching From Treated Wood ................................................................................ 29 4.1.2 Water Quality .......................................................................................................... 30 4.2 Environmental Exposure Pathways ................................................................................ 31 4.3 Ecological Effects Assessment ....................................................................................... 31 4.3.1 Ecotoxicology Endpoints ........................................................................................ 31 4.4 Exposure Analysis Plan .................................................................................................. 33 4.4.1 Aquatic and Terrestrial Wild life Exposure Estimates ............................................ 33 4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 33 4.5 Effects Analysis Plan ..................................................................................................... 35 5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 35 6 Optional Label Changes ........................................................................................................ 36 7 Next Steps .................................................................................................................... ......... 36 8 References .................................................................................................................... ......... 37

Appendix A Toxicology Profile ............................................................................................... 41Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 6 of 68 Appendix B Environmental Fate ............................................................................................. 53 Appendix C Ecotoxicology Profile .......................................................................................... 57 Appendix D Screening Level Down-the-Drain Analysis ........................................................ 64 Appendix E Product Chemistry ............................................................................................... 65 Appendix F Comments Received Concerning th e Preliminary Work Plan ............................ 66

List of Tables

Table 1 jAnticipated Risk Assessments and Da ta Needs for Registration Review: TCMTB ....... 9 Table 2 j Anticipated Regist ration Review Schedule .................................................................... 9 Table 3 j Chemical Identification of TCMTB ............................................................................. 10 Table 4 j Physical-Chemical and Envir onmental Fate Properties for TCMTB ........................... 11 Table 5 j TCMTB Registered Antimicrobial Uses ...................................................................... 13 Table 6 j TCMTB Registered Agricultural Uses ......................................................................... 14 Table 7 j Studies Anticipated as Needed for the Registration Review of TCMTB ..................... 17 Table 8 j Data Needs Already Required by the May 19, 2010 Data Call-In for the TCMTB RED*........................................................................................................................... .................. 19 Table 9 j Existing Toxicological Endpoints ................................................................................. 21 Table 10 j Occupational Handler Scenarios to be Assessed during Registration Review ........... 25 Table 11 j Residential Handler Ex posure Scenarios for TCMTB ............................................... 27 Table 12 j Residential Post-Applicati on Exposure Scenarios for TCMTB ................................. 28 Table 13 j Identification of Major Degradates of TCMTB .......................................................... 30 Table 14 - Ecological Effects Endpoints for the Ecological Risk Assessment. ............................ 32 Table 15 - Summary of Screening Level Down-the -Drain Analysis for Aquatic Organisms ...... 33Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 7 of 68 

## 1 Introduction

This document is the United States Environmen tal Protection AgencySs (USEPA, EPA or mthe agencyn) Final Work Plan (FWP) for 2-(Thiocya nomethylthio)-benzothiazole, herein referred to as TCMTB. This document explains what EP A's Office of Pesticide Programs (OPP) knows about TCMTB, highlighting anticipated data a nd assessment needs, identifying the types of information that would be especially useful to the agency in conducting the review, and providing an anticipated timeline for completing TCMTBSs 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 sh aring this information in the docket, to inform the public of what it knows abou t TCMTB and what types of new data or other information would be helpful for the agency to receive as it moves toward a decision on TCMTB.



## 1.1 Statutory and Regu latory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the USEPA based on scientific data showing that they will not cause unreasonable risk s to human health or the environment when used as directed on produc t labeling. The registra tion review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effects to human health or the environm ent. Changes in scien ce, public policy, and pesticide use practices will occur over time. Th rough the registration review program, the agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Inform ation on this program is provided at http://www2.epa.gov/pesticide-reevaluation

The agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registra tion review begin at 40 CFR 155.40. The agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the agencySs opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are need ed to make a registra tion review decision. The TCMTB Preliminary Work Plan (PWP) was published on September 24, 2014 and the 60 day comment period ended on November 24, 2014.

Public comments received concerning the PWP and documents associated with this registration review can be viewed at http://www.regulations.gov in docket EPA-HQ-OPP-2014-0405.



## 1.2 Updates to the Work Plan
Since the publication of the PWP, the agency has made the following updates:Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 8 of 68 x Corrected formatting and typographical errors.

x Added footnote to Table 1, noting a dietar y (food) assessment may be necessary if toxicological points of de parture (PoDs) change.

x Revised Table 5 to account for the fact that one of the products used for wood preservation (EPA Reg. N o.1448-344) was cancelled in 2001.

x Table 7:

o Added three additional pollinator studies triggered by seed treatment uses and corrected month time frames for bee studies.

o Added requirement for surface residue dissipation study on pressure treated wood after verifying that several labels list pr essure treatment as an application method for the sapstain use.

x Removed Section 7, Guidance for Commenters.

The agency received comments from the Center for Biological Diversity (Center) during the public comment period on the initial docket. Th e CenterSs comments sought to confirm the agencySs coordination with the U.S. Fish and Wi ldlife Service and the National Marine Fisheries under Section 7 of the Endangered Species Ac t (ESA) to ensure that TCMTB does not jeopardize the continued existence of any listed species or result in adverse modification or destruction of critical habitat. No other comments were received during the initial docket comment period.

Please see Appendix F for the agencySs responses to this comment.

The comment received did not result in additiona l modifications to the anticipated data needs detailed in the TCMTB PWP. This documen t makes final the work plan for the TCMTB registration review process.

Table 1 and Table 2 below summari ze the issues relevant to this registration review case and the anticipated registration review schedule.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 9 of 68 Table 1 –Anticipated Risk Assessments and Data Needs for Registration Review: TCMTB

Risk Assessment Assessment Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed (See Table 7 for details)

Residue Chemistry Yes 2/28/2006 Updated Enforcement Analytical Method 3

Dietary (food) No 4 (see 3.2.2) 8/1/2006 None None

Dietary (drinking water) Yes 1 8/1/2006 New None

Occupational Handler Yes 4/19/2006 Updated Indoor Exposure Data Acute Neurotoxicity 2 Immunotoxicity 2 90-Day Neurotoxicity 2 90-Day Inhalation 2

Residential Handler Yes 4/19/2006 Updated Indoor Exposure Data Acute Neurotoxicity 2 Immunotoxicity 2 90-Day Neurotoxicity 2 90-Day Inhalation 2

Residential Post Application - Incidental Oral and Dermal Yes 4/19/2006 Updated Indoor Surface Residue Dissipation Acute Neurotoxicity 2 Immunotoxicity 2 90-Day Neurotoxicity 2

Aggregate Yes 8/1/2006 Updated Acute Neurotoxicity 2 Immunotoxicity 2 90-Day Neurotoxicity 2

Cumulative No (see 3.4.2) N/A None None

Ecological Yes 2006 RED for sapstain and seed treatment
uses; N/A for other

uses Updated for sapstain and seed
treatment uses New for other

uses See Table 7

N/A = Not applicable Table 1 is a summary of the anticipated ri sk assessments and data needs for Registra tion Review. For data called in through the post-RED Data Call-In (DCI), see Table 8

. 1 Pending receipt and review of environmental fate data.

2 Data anticipated to be required for both antimicrobial and agricultural uses.

3 Data anticipated to be requi red only for agricultural use.

4 May be necessary if toxicological points of departure (PoDs) change.

Table 2 – Anticipated Regi stration Review Schedule
Anticipated Activity Target Date* Completion Date Phase 1: Openin g the Docket Open Docket and 60-Day Comment Period for Preliminary Work Plan 2014-09 09-24-14 Close Public Comment Period 2014-11 11-24-14 Phase 2: Case DevelopmentDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 10 of 68 Issue Final Work Plan 2015-03 2015-03

Issue Data Call-In (DCI) 2016-03

Receive Data to be Considered in Risk Assessment 2018-03

Open 30-Day Public Comment Period fo r Preliminary Risk Assessment(s) 2019-09

Close Public Comment Period 2019-10
Phase 3: Registration Review Decision and Implementation
Open 60-Day Public Comment Period for Proposed Decision 2020-03

Close Public Comment Period 2020-05

Issue Final Decision 2020-09

Begin Post-Decision Follow up 2020
Total (years) 6 *The anticipated schedule will be revised as necessary ( e.g ., need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case).



## 1.3 Case Overview
The docket for TCMTB (case 2625) has been established at http://www.regulations.gov in docket number EPA-HQ-OPP-2014-0405.



## 1.4 Chemical Identification and Properties
Table 3 presents the active ingredient to be assessed in case 2625: 2-(thiocyanomethylthio) benzothiazole (TCMTB) (PC Code 035603).

Table 3 – Chemical Identification of TCMTB

Chemical Name TCMTB Chemical Classification Mercaptobe nzothiazole; Thiazole; Thiocyanate
PC Code 035603
CAS Number 21564-17-0 Molecular Formula C 9 H 6 N 2 S 3 Molecular Weight (grams/mole) 238.352295

Molecular Structure

The TCMTB product chemistry information relevant to risk assessment is summarized in Table 4, and the details of the product chem istry (Source: MRIDs 41612003, 41612001, 41612002,Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 11 of 68 41612003, 42059701, 42059702, 42324501, 42407401) and environmental fate information are discussed in Appendix E a nd Appendix B , respectively.

Table 4 – Physical-Chemical and Envi ronmental Fate Properties for TCMTB

Parameter TCMTB
PHYSICAL/CHEMICAL CHARACTERISTICS Boiling point 191 o C, decomposes before boiling Density 1.376 g/cm 3 Octanol-water partition coefficient (K ow ) 3.22 at 25 ஈ C; highly bioaccumulative, but depurates within 28 days Solubility in water 45 ± 15 mg/liter at 25 ஈ C Vapor pressure (PAI) 2.34 x 10 -6 mmHg ENVIRONMENTAL FATE PROPERTIES (Degradates listed in Appendix B) Mobility Organic Carbon Partitioning Coefficient (K oc ) 283-7896 in 5 soils Persistence in Water (half-life)

Hydrolysis at 25 o C Stable at pH 5; degrades at pH 7, and 9 with a half-life of 2.1 days (MRIDs 423861-01 and 434376-01)

Aqueous photolysis at 25 o C Half-life at pH 5 is 1.5 hours. (MRID 426309-01 ) Aerobic aquatic metabolism Half-lif e 2 to 7 days. (MRID 425086-01) Anaerobic aquatic metabolism half-life Half-life of 2.7 days (MRID 428154-01) Persistence in Soil (half-life) Soil photolysis (days) Not required (See Appendix B) Aerobic soil metabolism at 25 o C Half -life of 1.4 days; (MRID 435322-01) Anaerobic soil metabolism Not required (See Appendix B) Persistence in WWTP (% removed) Ready biodegradation No data submitted, anticipated data requirement Adsorption/Desorption or Batch Equilibrium (K d ) 0.99 in sand to 62.7 in silt loam Kdes: 1.9 to 79.2 (MRID 426314-01)



## 1.5 Use/Usage Description

1.5.1 Registrations There are 26 EPA-registered products that contai n TCMTB as an active ingredient (a.i.). One end-use product has agricultura l uses: EPA Reg. No. 2935-389 is a fungicide seed treatment for rice, cotton, and safflower. With the exception of EPA Reg No. 1448-408, which is formulated as a wettable powder in water soluble packag ing, all of the products containing TCMTB are formulated as liquids. It shoul d also be noted that one product listed in EPASs database as a wettable powder (EPA Reg. No. 1448- 376) is actually a liquid. Th e label lists a product weight of 1.0 kg per liter and includes use direc tions that are give n in fluid ounces.

During registration review, the agency will work w ith registrants to clarify whether labels and use patterns are or are not inte nded for food or non-food contact.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 12 of 68 

### 1.5.2 Summary of Registered Uses Table 5 and Table 6 present a listing of the re gistered uses of TCMTB. EPA Reg. No. 264-965 was cancelled on 1-15-14. 1 This registration had the last seed treatment for the following agricultural commodities: wheat, barley, oats, sorghum, corn, and sugar beets. With the exception of the paint and textile uses, which were deemed ineligible for reregistration, and the cancelled seed treatment commodities, the uses are th e same as the uses that were assessed in the 2006 Reregistration Eligibility De cision (RED). The paint uses have been removed from all labels; however, the textile use is still include d on one end use product labels (#1448-440) and four formulation intermediate labels (1448-401, 1448-403, 1448-405, 1448-407) and must be removed. The agency has received documentation from the registrant of their intent to cancel the textile use and anticipates that the final cancelation order will become effective prior to issuance of the data call-in for this regi stration review. With the exception of the textile use, all of the uses listed in Table 5 will be assessed in this registration revi ew. TCMTB can be applied by the following application methods: open pour, brush, sp ray, dip treatment and pressure treatment.

1.5.2.1 Antimicrobial Uses TCMTB products are used in commercial/instituti onal premises and residential and public access areas. As an antimicrobial pesticide, TCMTB is used largely as a materials preservative (e.g., leather products and hides, pulp/paper produc ts, surface coatings, adhesives, caulks, and sealants), and also as a wood preservative a nd in industrial processes and water systems. TCMTB is a slimicide regulated by the FDA ( 21 CFR 176.300) for controlling bacteria, fungi and yeasts, which cause deterioration of paper and paperboard products.

1.5.2.2 Agricultural Uses TCMTB is registered for use as an agricultural pe sticide for seed treatment (on rice, safflower, and cotton). NUSAN® 30 E.C. (EPA Reg. N o. 2935-389) contains 2.635 pounds of TCMTB per gallon. NUSAN ® 30 E.C. is recommended for the c ontrol of seed-borne fungi that impair the germination and seedling development of cotton, rice and safflower. It is effective against Rhizoctonia

, Pythium

, Fusarium , and certain other fungi. NUSAN® 30 E.C. can be applied directly to the seed from the drum or as an agitated dispersion in wa ter. The recommended maximum rates may be dispersed in as much as 16 fl. oz. of water and applied to 100 lbs. of seed.

1 February 26, 2014 j Published the Product Cancellation Order for Certain Pesticide Registrations in the Federal Register (79 FR 10800) (FRL-9905-34)Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 13 of 68 Table 5 – TCMTB Registered Antimicrobial Uses

Use Application Method Application Rate (ppm a.i.) Industrial Process and Water Systems
Cooling Tower Wood j Circulate in Place Treatment Cooling Tower Wood j Surface Treatment Cooling Water Systems - Initial Treatment Cooling Water Systems j Maintenance Treatment

Oil Drilling Fluids and Muds Oil Secondary Recovery Fluids

Waste water treatment systems Open Pour Brush, Spray

Open Pour Open Pour

Open Pour Open Pour

Open Pour 15 to 45 700 to 2,100 3 to 45 1 to 10

230 to 750

3 to 28

9
Material Preservative

Fuel Oils, Crude and Refine

Leather - Treatment Water Leather j Wet Pelts Leather - Finishing Pastes and Fat liquors Leather- Green or Fleshed Hides and Skins Leather - Hides and Skins Leather - Split and Shaved Leather - White Lime Stock

Metal Working Fluids at MachinesMetal Working Fluids in Storage TanksPaper Mills - Additives Paper Mills - Bacteriostatic Paper Paper Mills - Mold Resistant Paper Paper Mills - Mulch Paper Paper Mills - Pulp Preservation Paper Mills - White Water or Stock

Particle Board Pigment Slurries, Adhesives, Caulks and Sealants Surface Coatings, Sealants, and Wall Covering Adhesives Textiles 1 Open Pour Open Pour

Open Pour Open Pour Open Pour Open Pour Open Pour Open Pour Open Pour

Open Pour Open Pour

Open Pour Open Pour Open Pour Open Pour Open Pour Open Pour

Open Pour Open Pour Open Pour Open Pour 3 to 5 5 to 12

600 2,100 750 to 1,040

160 to 240 20 600 250 to 600

75 375

40 9,000 300 750 600 25

300 to 3,000 750 to 2,500 15,000 6,000 to 7,500
Wood Preservatives
Wood Preservation Sapstain Control (Millwork, shingles, lumber, logs, poles, post and timbers) Dip, Spray, Brush, Pressure 2,200 to 16,200

1 The textile use was deemed ineligible in the RED bu t it remains on one product label (1448-440) and four
formulation intermediate labels (1448-401, 1448- 403, 1448-405, 1448 -407). The agency has received documentation from the registrant of their intent to cancel the textile use and anticipates that the final cancelation order will become effective prior to issuance of the data call-in for this registration review.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 14 of 68 Table 6 – TCMTB Registered Agricultural Uses

Crop Application Rate (fl oz product/100 lbs-seed) Max. Seeding Rate (lbs-seed/ac) 1 Rate (lbs a.i./ac)

Cotton 5 18.9 0.0195

Safflower 2 35 0.0144

Rice 1.25 129 0.0332

1 Maximum Seeding Rates are based on T-REX model (version 1.5.2)



### 1.5.3 Usage Information According to the Kline Report, approximately 1.2 million pounds of TCMTB for antimicrobial uses was sold in 2004. The Kline Report accounts for the antimicrobial uses of TCMTB. The metal working fluid use, the leather use and the paper use accounted for approximately 10, 14 and 76 percent of sales, respectively (Kline, 2005). No public sales or usage data were available for the agricultural uses.



## 1.6 Regulatory History
The first pesticide product containing TCMT B was registered by the EPA on January 21, 1980. The agency assessed TCMTB as a dual-use chem ical and completed a RED in 2006. The agency issued a post-RED generic data call-in (GDC I-035603-29761) and product specific data call-in (PDCI-035603-29762) on May 19, 2010. 2



### 1.6.1 Tolerance Information

There are 25 tolerances listed in 40 CFR 180.288 for TCMTB. The agency anticipates reviewing all active tolerances/exemptions duri ng the registration review process.

1.6.1.1 Antimicrobial Uses For the active ingredient TCMT B, EPA has no tolerances or exemptions from tolerances established for use antimicrob ial uses under the Federal Food, Drug and Cosmetic Act (FFDCA) Section 408. TCMTB has been cleared as a food additive by the US Food and Drug Administration (US FDA) under FFDCA Section 409 fo r use as an antibacterial preservative in paper and paperboard co mponents (21 CFR 176.300).

1.6.1.2 Agricultural Uses The current tolerance expression does not comply with OPPSs Health Effects DivisionSs (HED) policy on tolerance expression. In addition, HE D reviewed some recently submitted data for TCMTB and it appears that a tole rance for cotton gin byproduct ma y need to be established. Established tolerances on cott on, undelinted seed, rice grain, a nd safflower grain should be maintained to support the seed treatment uses for TCMTB on cotton, rice and safflower. The

2 For the studies required through the post-RED DCI, see Table 7.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 15 of 68 registrant has voluntarily cancelle d uses of TCMTB as a fungicid e on barley, sugar beets, corn, oats, sorghum, and wheat. 3 The agency is working with registrants to revoke the tolerances for the cancelled commodities. There are no Code x/Canadian Maximum Residue Limits (MRL) established on TCMTB.



## 1.7 Incidents

1.7.1 Human Health Individual Incident Reports

Incidents that are rated as mode rate (HC) or higher are report ed in individual reports which include information regarding the causes of the incident and symp toms experienced. In the case of TCMTB, six human health indi vidual incident reports are list ed in the OPP Incident Data System (IDS) for the period from 1/1/2006, when the RED was written, to the present (search conducted on 6/17/14). All incident s are classified as human m oderate (HC). Summaries of these incidents are included below. These summa ries are provided for information purposes only to aid in risk management and are not meant to be a formal in terpretation of cause and effect.

x A chemical service company worker experien ced migraines, nosebleeds and skin rash after working on dosing equipment in the chemical room of a paper mill. The rash became more frequent over time and it bega n to occur when the worker was in other areas of the mill where only the diluted product was used.

x Mill employees handling leaking drums of a TCMTB product without PPE in Singapore experienced skin irritation and burns. The drums were horizontal and leaked around the
cap.

x A sapstain treatment worker alleged that TCMTB products have caused his knees to swell. He maintained dip chemicals for 10-11 yrs.

x In a lawsuit; plaintiff alleged that use of a TCMTB product and other products, caused several injuries, including lung fibrosis. The plaintiff treated oil fracking tanks.

x A reporter working as a temporary worker fo r one day in a tannery received a facial chemical burn when treating mwet bluesn (a stage of leather pr oduction) with a TCMTB product.

x Paper mill workers experienced dermal irritation in the face, eye irritation, and burning skin during a trial using a TCMTB product. The mill was also running a trial of an ammonium sulfate product.

Aggregate Incident Reports

Incidents that are rated as minor (HD) or that cannot be rated (HE) ar e reported in aggregate reports which are listings of the incidents for a manufacturer or distribu ter over a certain time period (often quarterly). Typically these reports only contain basi c information such as the date, location and product involved and more detailed in formation such the cause of the incident or symptoms experienced are not included. In the case of TCTMB, there are 12 aggregate incidents

3 February 26, 2014 j Published the Product Cancellation Order for Certain Pesticide Registrations in the Federal Register (79 FR 10800) (FRL-9905-34)Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 16 of 68 listed in the IDS for period from 1/1/2006 to the present (search conducted on 6/17/14). All of these incidents are classified as human minor (HD) and there is no additional information.



### 1.7.2 Ecological No ecological incidents have been reported in the agencySs Incide nt Data System as of April 22, 2014. A review of the Ecological Incident Inform ation System (EIIS, version 2.1) and the Avian Monitoring Information System (AIMS) wa s completed on August 8, 2014, and no ecological incidents were identified. Incident databases wi ll be reviewed again at the time of the risk
assessment.


## 2 Anticipated Data Needs

Several studies were required from the assessm ent of TCMTB in the 2006 RED. In addition to those already-required RED DCI data, the following studies as listed in Table 7 are expected to be needed for the registration review of TC MTB. Table 8 outlines the data requirements imposed by the post-RED DCI issued on May 19, 2010. The agency anticipates reviewing all data received in response to the post-RED DCI as well as data required for this registration review prior to conducting the registration review risk assessments for TCMTB.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 17 of 68 Table 7 – Studies Anticipated as Needed for the Registration Review of TCMTB

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

Requirement Applicable Exposure Scenario

830.1800 Enforcement analytical method TGAI 12 Residue Chemistry Seed treatment Seed treatment

835.3110 1,2 835.3220 835.3240 835.3280 Ready biodegradability or one of three biodegradation in activated sludge simulation tests Degradates 8 24 Fate and persistence in WWTPs Down the drain
assessment Material Preservatives Metal Working Fluids Industrial Processes and Water Systems Wood Preservatives Toxicity to WWTP organisms

850.1350 5 Mysid chronic toxicity

Degradates 7 12

Aquatic organisms Materials Preservatives, Wood Preservatives, Industrial Processes and Water Systems Aquatic environment 850.1400 5 Fish early-life stage, estuarine/marine species 12

850.1735 4 Whole sediment subchronic toxicity, freshwater invertebrates (2 spp.) 12

850.1740 4 Whole sediment subchronic toxicity, estuarine/marine invertebrate 12

850.2100 Avian acute oral (passerine) TGAI 12 Terrestrial organisms Seed treatment

Terrestrial environment 850.3020 (Tier 1) Honey bee acute contact toxicity TGAI 18

Beneficial insects Wood preservatives Seed treatment OECD 213 (Tier 1) Acute oral toxicity study with adult honey bees TGAI 18

Seed treatment OECD 237 (Tier 1) Acute oral toxicity study with honey bee larvae TGAI 18

OECD Draft GD 25 February 2014 4, 9 (Tier 1) Honey bee larval toxicity test, repeated exposure TGAI 18

Non-Guideline (Tier 1) 4, 9 Honey bee adult chronic oral TGAI 18

Non-Guideline (Tier 2) 4, 9 Semi-field testing for pollinators (tunnel or colony feeding studies) TEP 24Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 18 of 68 GLN Study Name Test Substance Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data

Requirement Applicable Exposure Scenario

Non-Guideline Study (Tier 2) 4, 9 Field trial of residues in pollen and nectar TEP 24

Non-Guideline (Tier 3) 4, 9 Field testing for pollinators TEP 24

850.3300 3 or OECD 209 Activated sludge, respiration inhibition test Degradates 8 24 Fate and persistence in WWTPs Down the drain
assessment Material Preservatives Metal Working Fluids Industrial Processes and Water Systems Wood Preservatives Toxicity to WWTP organisms

870.3465 90-Day Inhalation TGAI 24 Human Health All Use Sites (including seed treatment) All

870.6200 6 90-Day Neurotoxicity TGAI 24 Human Health All Use Sites (including seed treatment) All

870.6200 Acute Neurotoxicity TGAI 24 Human Health All Use Sites (including seed treatment) All

870.7800 6 Immunotoxicity TGAI 24 Human Health All Use Sites (including seed treatment) All

875.1200 875.1400 Indoor Exposure j Dermal and Inhalation TGAI or surrogate 24 Occupational Handler Wood Pr eservative Pressure Treatment

875.1200 875.1400 Indoor Exposure j Dermal and Inhalation TGAI or surrogate 24 Occupational and Residential Handler Materials Preservative j Wall Covering Adhesive Brush/roller application

875.2300 Indoor Surface Residue Dissipation (wood surface residues) TGAI 12 Residential Post Application Sapstain Control (Pressure Treatment Only) Dermal and Incidental Oral Exposure to Pressure Treated Wood

1 The anticipated data requirement for degradates could be waived in cases where the degradates are less toxic than the parent co mpound.

2 The results of the ASRI test will determine which of these four biodegradation tests is/are anticipated to be required. If the ASRI test EC 50 is less than or equal to 20 mg/L, then either the (i)Biodegradation in Activated Sludge Study or (ii) Simulation Test j Aerobic Sewage Treatment: A. Act ivated Sludge Units or (iii) the Porous Pot Test is expected to be required. If the ASRI test EC 50 is greater than 20 mg/L, then the registrant woul d likely be required to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test j Aerobic Se wage Treatment: A. Activated S ludge Units or c) the Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to be r equired. If, however, the antimicrobial fails the Ready Bi odegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test j Ae robic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study would likely be required.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 19 of 68 3 EPA published draft guidance under guideline 850.6800 and has since published final guidance for this study under guideline 850.3300: http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPPT-2009-0154-0021 . OECD Test Guideline 209 can also be used as guidance for this study, available online at http://www.oecd-ilibrary.org/content/book/9789264070080-en

. 4 The anticipated GDCI will request that the registrant(s) submit a protocol for review by the agency prior to conducting of the study.

5 The anticipated GDCI will request that testing be conducted with the most sensitive organism (either freshwater or estuarine/m arine vertebrates, or freshwater or estuarine/marine invertebrates), as determined from the results of the acute toxicity tests (acute EC50 freshwater invertebrate s; acute LC50/EC50 estuarine and marine organisms; acute freshwater fish LC50).

6 All 90-day subchronic studies in the rodent can be designed to simultaneously fulfill the requirements of the 90-day neurotoxic ity and/or immunotoxicity studies by adding separate groups of animals for testing of neurotoxicity and/or immunotoxicity parameters.

7 Specific to the following degradates: 2- mercapto-benzothiazo le (2-MBT or MB)

8 Specific to the following degradates: MB and benzothiazol sulfonic acid (BTSA)

9 Higher tier studies (Tier 2 and Tier 3) may be required pending the results and evaluation of Tier 1 studies. Higher tier stu dies may be required if the ratio of the EEC and larval or adult bee acute LD50 >0.4 or the ratio of the EEC and chronic NOAEC >1. Incident data and/or compelling open literature studies can also serve as rationale for requiring Tier 2 and Tier 3 studies. Measured residues in po llen/nectar typically required to refine sc reening level exposure estimates.
Table 8 – Data Needs Already Required by th e May 19, 2010 Data Call-In for the TCMTB RED*

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

835.4200 Anaerobic Soil Metabolism 24 Environmental Fate

Agricultural Premises and Equipment Commercial, Institutional and Industrial Premises and Equipment Residential and Public Access Premises Materials Preservatives Industrial Processes and Water Systems Wood Preservatives 835.6200 Aquatic Field Dissipation 24 850.1400 Fish early-life stage toxicity test 12

Ecological Effects 850.1500 Fish life cycle toxicity 24 850.3030 Honey Bee toxicity of Residues on Foliage 12 850.4100 Terrestrial plant toxicity, Tier 1 (seeding emergence) 12 850.4225 Seedling emergence, Tier II 12 850.4250 Vegetative vigor, Tier II 12 850.5400 Algal toxicity, Tiers I and II 12 860.1300 Nature of the Residue j Plants, Livestock 24 Residue Chemistry 860.1500 Crop Field Trials (Honey) 24 860.1500 Crop Field Trials (Honeycomb) 24

875.1200 875.1400 Indoor Exposure j Dermal and Inhalation 24 Occupational Handler Materials Preservatives (did not include wall covering adhesive use site in the brush/roller exposure scenario) Industrial Processes and Water Treatment Wood Preservatives (did not include pressure treatment exposure scenario)Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 20 of 68 GLN Study Name Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data Requirement

875.1600 Application Exposure Monitoring Data Reporting This study is no longer required. This report is addressed in the submission of the remaining exposure data requirements.

875.2800 Description of Human Activity 12 All human exposure Materials Preservatives Industrial Processes and Water Treatment Wood Preservatives Special Study Leather Leaching N/A (study has been submitted) Residential Post Application Leather

*Post-RED DCI did not require data for any degradates.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 21 of 68 

## 3 Human Health Risk Assessment

The agency anticipates the need to conduct a human health risk assessment for TCMTB. The agency expects to require additional data for us e in conducting the regist ration review. Section 3 below provides information for the antimicrobial and the agricultural uses of TCMTB. For more detailed information on the agricultural uses of TCMTB, please refer to the Human Health Risk Assessment Scoping Document in Support of Regist ration Review, also poste d in the registration review docket at http://www.regulations.gov in docket EPA-HQ-OPP-2014-0405.



## 3.1 Toxicological Endpoints

EPA anticipates the need to revise the existing t oxicological endpoints as pa rt of this registration review. Table 9 presents the endpoints used in EPASs most recent human health risk assessment in support of the 2006 RED. As previously stated, toxicological studies we re identified as data gaps in the RED and identified in the registra tion review as anticipat ed data needs based on currently registered uses. All av ailable information including existing toxicology studies, valid scientific literature, and the studies that are expe cted to be required for registration review will be considered in establishing the endpoints to be us ed in the registration re view risk assessment. A detailed description of the toxicity studies is provided in Appendix A .

Table 9 – Existing Toxicological Endpoints

Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Target Margin of Exposure (MOE), Uncertainty Factor (UF), FQPA Safety Factor (SF) Study and Toxicological Effects

Acute Dietary (all populations including infants and

children) NOAEL= 25.1 mg/kg/day 83.55% ai purity UF = 100 (10x inter-speciesextrapolation and intraspecies variation)

FQPA SF = 1x Acute PAD = 0.25 mg TCMTB/kg/day Developmental toxicity study in rats (MRID 00154295, 92179009 (1985)) Maternal LOAEL = 76.5 mg TCMTB/kg/day,

based on clinical signs of toxicity (ventral alopecia, rough coat, dyspnea/wheezing, oral discharge, diarrhea/loos e stool, urine staining, piloerection, and hunched gait). Acute Dietary (females 13-49) An endpoint specific for females 13-49 was not identified because the Acute Dietary endpoint for all populations is protective of developmental effects.

Chronic Dietary (all populations) LOAEL = 3.8 mg/kg/day 81.6% ai purity UF = 300 (10x inter-speciesextrapolation and intraspecies variation, 3x for use of a LOAEL)

FQPA SF = 1x Chronic PAD = 0.01 mg ai/kg/day Chronic toxicity study in dogs (MRID 41342201, 92179008 (1989)) LOAEL = 3.8 mg/kg/day (males), based on decreased body weight gain, decreased white cells, monocytes, and plasma ALT; decreased uterine weight in females.

Short- andIntermediateTerm NOAEL=16.2 mg ai/kg/day MOE = 100 Developmental toxicity study in rabbitsDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 22 of 68 Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Target Margin of Exposure (MOE), Uncertainty Factor (UF), FQPA Safety Factor (SF) Study and Toxicological Effects

Incidental Oral

(1-30 days; 30 days-6 months) 81% ai purity (20 mg TCMTB/kg/day) (MRID 40075101, 40075102, 92179011 (1986))

LOAEL = 32 mg ai/kg/day (40 mg TCMTB/kg/day), based on decreased body weight gain and food consumption in maternal animals.

Dermal (all durations)

(1-30 days; 30 days-6 months;

> 6 months) NOAEL= 25 mg/kg/day

82.33% ai purity (20.6 mg ai//kg/day) MOE = 100 (ST and IT)

MOE = 300 (LT) 21-Day dermal toxicity study in rats (MRID 41655801)

LOAEL = 100 mg TCMTB/kg/day (82.3 mg ai/kg/day), based on decreased body weight gain, food consumption, and hematological and clinical chemistry changes

Inhalation

(short- andintermediateterm) NOAEL=16.2 mg ai/kg/day

81% ai purity (20 mg TCMTB/kg/day)

Absorption=100% (inhalation and oral equivalent) MOE = 300 (ST and IT) Developmental toxicity study in rabbits (MRID 40075102)

LOAEL = = 32 mg ai/kg/day (40 mg TCMTB/kg/day), based on decreased body weight gain and food consumption in maternal animals

Inhalation (long-term) LOAEL = 3.8 mg/kg/day

81.6% ai purity Absorption=100% (inhalation and oral equivalent) MOE = 1000 Chronic toxicity study in dogs (MRID 41342201, 92179008 (1989))

LOAEL = 3.8 mg/kg/day (males), based on decreased body weight gain, decreased white cells, monocytes, and plasma ALT in males; decreased uterine weight in females.

Carcinogenicity The CPRC concluded that TCMTB should be classified as Group C - possible human carcinogen - and recommended that for the purpose of risk char acterization, the Reference Dose (RfD) approach should be used for quantitation of human risk. This was based on statistically significant increases in tumors in both sexes of the Sp rague-Dawley rat: testicular interstitial cell adenomas in males and thyroid C-cell adenomas in females.



## 3.2 Dietary Exposure
The most recent dietary exposure assessment for TCTMB was done in support of the 2006 RED and assessed risks to food-cont act pulp and paper products. Since risks of concern were not identified at that time and no additional uses to contribute additional exposure from food contactDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 23 of 68 have been registered, the agency does not antici pate the need to update the dietary (food only) assessment. With respect to drinking water e xposure, the agency did not conduct a drinking water assessment in support of the 2006 RED and may need to conduct an assessment pending the results of the environmental fate data review.



### 3.2.1 Residue Chemistry (Agricultural Uses Only)

There is only one active agricu ltural-use product (EPA Reg No. 2935-389) registered for use for seed treatment of rice, safflower and cotton. No additional residue chemistr y data are anticipated to be required for the antimicrobial uses of TCMTB.

HED previously determined that the TCMTB use as seed treatment is a food use. A number of deficiencies, in particular data on storage stability, field trials, metabolism studies, livestock feeding studies and requirement for updating the enforcement method, were noted in the last HED summary document chapter for 2006 (S. Ary, D322617). Only one of these deficiencies (cotton metabolism study) has been directly addre ssed with data since the issuance of the RED. Previously submitted metabolism studies on seed treated corn, cotton, safflower and wheat were inadequate because identification and/or characte rization of parent and/or metabolites were not performed and data on solvent and TCMTB concentr ation in the treatment solution as well as the seed treatment rate were not provided. In res ponse to deficiencies in the RED, the registrant submitted a cotton metabolism study. HED reviewed the cotton metabolism study and deemed that study to be scientifically acceptable and adequate for regulatory purposes (T. Bloem, D418804, 8/26/14). The study was conducted at 3.2x the current maximum cotton label rate. HED notes that the cotton maximum rate is 4x and 2.5x the maximum label rate for rice and safflower, respectively. Total radioactive residues (TRRs) were 0.002 ppm and 0.024 ppm in undelinted cotton seed and leaves/stems, respect ively. The identification of residues in leaves/stems were attempted; however, because of individual unknowns were <0.004 ppm, the analysis of the extract did not result in the identif ication of residues. Based on TRR of 0.002 ppm in undelinted cotton seed and adjusting for the rate differences between cotton, rice, and safflower, HED used the cotton metabolism data, in corporated rate differences between the crops and applied theoretical concentra tion factors to the cotton TRR va lues to estimate the potential residues of TCMTB in food and feed parts of rice, safflower and cotton from TCMTB seed
treatment.

Acceptable data have been submitted demonstr ating that the metabolite profile in cotton metabolism study was stable in the extract of im mature plants for ~6 months. Therefore, no additional storage stability data are anticipated to be needed for any cr ops. Additionally, since the only remaining active uses are rice, safflower and cotton, no field trial data for sugar beets are expected to be required. Fu rthermore, based on the negligible residues in feed items, HED expects negligible, if any, residues in livestock ti ssues; therefore, a livestock feeding study is not expected to be required. The only outstanding deficiency is the enforcement method. The available enforcement method (Met hod B in PAM Vol. II.) is outda ted and uses toxic reagents; therefore, an updated enforcement method which does not use toxic reagents is anticipated to be required.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 24 of 68 

### 3.2.2 Antimicrobial Uses

3.2.2.1 Food

The only approved antimicrobial use of TCMTB that may result in residues in food is as an antibacterial preservative of f ood-contact paper and paperboard. Acute and chronic dietary risks associated with this use were summarized in the 2006 RED and were below the agencySs level of concern. Dietary risks may need to be reassessed if there is a change in the acute or chronic dietary points of departure, and/ or if aggregate risks exceed the agencySs levels of concern. No residue chemistry data are expected to be needed at this time to characterize residues of TCMTB in food.

3.2.2.2 Drinking Water

A drinking water assessment has not been condu cted for TCMTB in the past. However, for several approved uses (including water cooling syst ems) the agency cannot rule out the potential for TCMTB to enter drinking wate r. There are uncertainties with respect to the residues of concern in drinking water, the magnitude of th ese potential residues concern, their mammalian toxicities, how persistent they will be, and if they are likely to pass through a wastewater treatment plant (WWTP) is unknown. Therefore, the agency anticipat es needing certain environmental fate data listed in Section 4 of th is PWP. These data will be useful to determine whether, and to what extent, residues of TCMTB pass through a WWTP. The agency anticipates using these data and/or other sources of information during the risk assessment stage of registration review to determine the potential for discharged residues of TCMTB to result in human dietary exposure via drinki ng water, which may trigger a drinking water assessment. No residue chemistry data are expected to be needed at this time to characterize residues of TCMTB in drinking water.



### 3.2.3 Agricultural Uses, Food and Drinking Water Acute and chronic dietary risk assessments were most recently performed for TCMTB using the Dietary Exposure Evaluation Model (DEEM-FCI D) version 2.03 (2/28/06, D324018). This model uses food consumption data from the U. S. Department of AgricultureSs Continuing Survey of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. These acute and chronic analyses were conservative and assume d tolerance level residue s, empirical processing factors, 100% crop treated values for all commodities, and the FQ PA Index Reservoir Screening Tool (FIRST) estimated peak drinking water co ncentration. The highest rate was from the safflower seed treatment scenario. The calculate d acute exposure to f ood and water resulted in estimated risks which were < 2% of the acute population adjusted dos e (aPAD) at the 95th percentile for all population subgroups. Chronic di etary risk calculated from exposures to food and water resulted in estimated risks which were < 17% of the chronic population adjusted dose (cPAD) for the U.S. population and all popula tion subgroups, with the highest exposed population subgroup being children 3-5 years old at 17% of the cPAD. TCMTB is classified as mpossible carcinogenn and the reference dose (RfD ) approach should be used for quantitation of human risk. Therefore, quantif ication of risk using a non-lin ear approach (i.e. the chronic reference dose (cRfD)) will adequately protect fo r all chronic toxicity, including carcinogenicityDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 25 of 68 that could result from exposure to TCMTB. An updated dietary (food and drinking water) risk assessment may be conducted during registration review if the toxico logical PoDs or UFs change, and/or updated drinking water assessme nt may be conducted if the values vary significantly from the values used in the current assessment.



## 3.3 Occupational and Re sidential Exposures
The agency anticipates the need to revise the Occupational Resi dential Exposure (ORE) assessment (EPA, 2006c) that was written for the TCMTB RED. The ORE assessment will need to be revised to account for the toxicology studi es that were submitted after the RED and to utilize the exposure and surface re sidue data that were required by the post-RED DCISs and are anticipated to be required for re gistration review of TCMTB.



### 3.3.1 Occupational Handler Exposure

3.3.1.1 Antimicrobial Uses EPA anticipates the need to revise the occupa tional handler assessment conducted in support of the 2006 RED. The exposures assessed includ e liquid pouring for industrial water systems treatment, oil and gas drilling fluids and material preservation, use of preserved materials such as paints and metal working fluids and wood preservative sapstain control applications. Both dermal and inhalation exposures were assessed and were considered to be of short to intermediate term in duration. With the exception of the paint uses which had dermal MOEs of 6 and 30 for airless and paint brus h application, respectiv ely, the dermal MOEs were greater than the target MOE of 100 and were not of concern. With the exception of the paint uses which had inhalation MOEs of 180 for airl ess sprayer application, the i nhalation MOEs exceeded 1000 and were not of concern. Based on the low MOEs for th e paint use, the RED specified that the paint use be cancelled, the paint uses have been removed from all TCMTB labels.

The exposure to machinists using metal working fluids treated with TCMTB was assessed as a long term exposure using the air c oncentration approach for inhala tion exposures and a thin film approach for the dermal exposure. The MOE for inhalation exposure was 31,000, which exceeded the target MOE of 1000 and the MOE for dermal exposure was 200, which exceeded the target MOE of 100.

Handler Exposures to Assess during Registration Review

The occupational handler scenarios that will need to be assessed for registration review are listed in Table 10.

Table 10 – Occupational Handler Scenarios to be Assessed during Re gistration Review

Scenario Exposure Route(s) Duration

Open pour application for material preservation and industrial process and water system treatment Dermal, Inhalation Short and Intermediate Term

Brush/roller application of TCMTB preserved wall covering adhesives Dermal, Inhalation Short and Intermediate TermDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 26 of 68 Scenario Exposure Route(s) Duration

Machinist exposure to TCMTB preserved MWF Dermal, Inhalation Long Term

Wood Preservationj Dip, spray and brush application Dermal, Inhalation Short and Intermediate Term

Wood Preservation j Pressure Treatment Dermal, Inhalation Short and Intermediate Term

3.3.1.2 Agricultural Uses TCMTB is registered for use for seed treatment on farm as well as commercial treatment for cotton, rice, and safflower seeds. There is potential for expos ure to TCMTB in occupational scenarios from handling TCMTB products during th e seed treating process (both commercial and on-farm) and a potential for post-application wo rker exposure from loading and planting seed previously treated with TCMTB. The registered product contains 2.635 lb active ingredient (ai) per gallon of product.

The occupational handler and post- application exposure scenarios a ssociated with the registered uses of TCMTB were not assess ed using current HED policies. There have been updates to several HED standard operating procedures (S OPs) including but not limited to primary and secondary handler unit exposures in SOP 14 and daily pounds of seeds tr eated per day in SOP 15. There is also a guidance document from the Biological and Econom ic Analysis Division (BEAD) that provides input values including seed count and seeding rate (most recently updated March 24, 2011). Revised occupational handl er and post-application exposure and risk assessments will be required for registration re view. These assessments will incorporate all updated toxicological PoDs, UFs/SFs, and a ll current policies and procedures.

In accordance with the updated Part 158 data requi rements (2007), a turf transferrable residue (TTR) study is required for all occupational (e.g. sod farms, golf courses, parks, and recreational areas) or residential turf uses. However, A TTR study is not anticipat ed to be required for TCMTB at this time since there are no registered or proposed turf uses.

The TCMTB database also lacks a DFR study (a pplicable to agricultu ral crops use). In accordance with the updated Part 158 data requi rements (2007), one or more DFR studies are required when a pesticide has residential or occupational uses that could result in postapplication dermal exposure. The potential for post-application exposures following the planting of TCMTB-treated seeds is unlikely because sustained levels of cont act with treated seed after it has been placed in the soil or other planting media would not be expected. No routine cultural practice required for the production of agricultur al commodities involves such an activity as defined in the no/low contact criter ia in the Worker Protection Standard (WPS). No quantitative post-application assessment is required for exposur e to treated seeds that have already been planted. Therefore, DFR studies are not anticipated to be needed for TCMTB at this time.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 27 of 68 

### 3.3.2 Residential Handler Exposures

3.3.2.1 Antimicrobial Uses

EPA will not need to revise the residential handler assessment conducted in support of the 2006 RED because the use (paint) that triggered the assessment was deemed ineligible for reregistration and all paint uses have been rem oved from product labels. EPA will need to assess the wall covering adhesive use, however, because it was not assessed in the RED.

The residential handler scenarios th at will need to be assessed for registration review are listed in Table 11.

Table 11 – Residential Handler Exposure Scenarios for TCMTB

Scenario Exposure Route(s) Duration Brush/Roller application of wall covering adhesive Dermal and Inhalation Short Term

3.3.2.2 Agricultural Uses

There are no residential uses of TCMTB. Th erefore, a residential risk assessment is not anticipated to be required.

Since TCMTB agricultural uses are limited to seed treatment applications, significant exposure from spray drift or throu gh volatility is not expected for this chemical.



### 3.3.3 Residential Post-Application Exposures

3.3.3.1 Antimicrobial Uses EPA anticipates the need to revise the reside ntial post-application a ssessment conducted in support of the 2006 RED. Residentia l post-application dermal and in cidental oral exposures to residues arising from contact with carpet and textiles (i.e. clothi ng and blankets) preserved with TCMTB were assessed using an ap plication rate of 6000 ppm. Th e MOEs for carpet were 4 for incidental oral exposure and 2 for dermal exposur e and were of concern because they were less than the target MOE of 100. The MOEs for dermal exposure to textiles were 6 for children and 9 for adults (assuming 5 percent residue transfer) and the MOE for incidental oral exposures was 21. These MOEs were also of concer n because they did not exceed 100.

The risks of exposure to leathe r products treated with TCMTB were assessed in the RED based upon preliminary leaching data submitted by the regi strant. These data suggested that the MOEs would exceed 100 and thus the risks would not be of concern.

Risks will also need to be assessed for toddler incidental oral and dermal exposure to wood pressure treated for sapstain control. These risks were not assessed in the RED because it was not known that TCMTB sapstain co ntrol treatments would be appl ied using pressure treatment. Sapstain control treatments are normally app lied using the dip or spray methods; however, two labels (EPA Reg. Nos. 1448-100 and 1448-341) indi cate that pressure treatment methods can also be used. In addition, the use sites liste d on these labels (millwork, shingles, lumber, logs, poles, post and timbers) include some sites, such as lumber, that could be associated with toddler
exposure.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 28 of 68 Though the textile use was deemed ineligible for reregistration in the 2006 RED, it remains on one product label (1448-440) and four formul ation intermediate labels (1448-401, 1448-403, 1448-405, 1448-407). The agency has received documenta tion from the registrant of their intent to cancel the textile use and anticipates that the final cancelation order will become effective prior to issuance of the data call -in for this registration review.

The post-RED DCI also required that a finalized transferable residue study be submitted for the leather use. This study has been submitted and w ill be used during registration review to assess the leather use.

The residential post application s cenarios that will need to be a ssessed for the registration review of TCMTB are listed in Table 12.

Table 12 – Residential Post-Applicat ion Exposure Scenarios for TCMTB

Scenario Exposure Route(s) Duration Exposure to Treated Leather Products De rmal Short and Intermediate Term
Exposure to Pressure Treated Wood Dermal Incidental Oral Short and Intermediate Term

3.3.3.2 Agricultural Uses

There are no residential uses of TCMTB. Th erefore, a residential post-application risk assessment is not anticipated to be required.



## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures

EPA anticipates the need to revise the aggr egate assessment conducted in support of the 2006 RED. Upon a reevaluation and sel ection of toxicological endpoint s, combined with the human health exposure assessments expected as a part of this registration review case, aggregate exposures will need to be assessed. This assessment will include dietary (food and water) exposures and residential exposures.



### 3.4.2 Cumulative Exposures

With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common me chanism of toxicity, EPA has not made a common mechanism of toxicity finding as to TCMTB and any other substances and TCMTB does not appear to produce a toxic metabolite pro duced by other substances. For the purposes of this registration review, therefore, EPA has not assumed that TCMTB has a common mechanism of toxicity with other substances. For informa tion regarding EPASs efforts to determine which chemicals have a common mechanism of toxicity a nd to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 29 of 68 

## 4 Environmental Risk Assessment

The agency conducted an environmental risk asse ssment for sapstain wood-preservative use for the RED (EPA 2006a). The assessment indicated that the amount of TCMTB leaching from treated wood and reaching the aquatic environmen t was sufficiently high to pose risks to aquatic organisms. The highest LOC exceedance was for chroni c risk to freshwater fish. LOCs also were exceeded for acute risks to listed and non-listed fres hwater and estuarine/marine fish and aquatic invertebrates. LOCs were not exceeded for aquati c plants. Risks to benefi cial insects and chronic risks to freshwater invertebrates and estuarin e/marine fish and inve rtebrates could not be assessed due to lack of ecotoxicity data.

The agency has not previously conducted a risk assessment that supports a complete endangered species determination for the antimicrobial or the agricultural uses of TCMTB. The ecological risk assessment planned during registration review will allow the agency to determine potential acute and chronic risks to aquati c and terrestrial organisms exposed to TCMTB transported from antimicrobial use sites into the aquatic environm ent. In addition, the assessment will allow the agency to determine potential acute and chroni c risks to aquatic and terrestrial organisms exposed to TCMTB from the agricu ltural use of seed treatment ( e.g., consumption of treated seed, consumption of plant or plant components fr om growing from treated seeds, contact with dust during planting, or runoff from fields containing treated se ed). The risk assessment will allow the agency to determine wh ether each use has 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designa ted critical habitats. When an assessment concludes that a pesticideSs use 'may a ffect' a listed species or its designated critical habitat, the agency will consult with the U.S. Fi sh and Wildlife Service and/or National Marine Fisheries Services (the Services), as appropriate.



## 4.1 Environmental Fate Assessment

TCMTB is not stable in surface waters with multiple degradation pathways. Although hydrolytically stable at pH 5, it degrades with a half-life of 2.1 days at pH 7 and pH 9. Photodegradation is even more rapid, with a half-life of 1.5 ho urs at pH 5. Under aerobic and anaerobic aquatic media, it is no t stable and degrades quickly w ith a half-life of 6.9 days and 2.7 days, respectively. In aerobic soil media, TCMTB is not stable, with a half -life of 1.4 days. For all aquatic degradation pathways, 2-Mercaptobe nzthiazole (MBT) was identified as a major degradate. It binds weakly with sandy loam, but has a moderately strong bond with silt loam soils. The environmental fate of TCMTB, includi ng degradates formed, is discussed in more detail in Appendix B.



### 4.1.1 Leaching From Treated Wood A 13-day aqueous availability (leaching) study evaluated the leaching of TCMTB from pine wood treated in the forest to determine th e quantity of TCMTB that may reach aquatic environments when fallen logs are removed by floa tation or are stored in quantity in areas of high rainfall. Wood samples were treated with TCMTB at 320 ppm and 601 ppm. The average amounts leached over the 13-day study were 0.927 ppm (0.29%) and 1.505 ppm (0.25%) for the low and high concentrations, respectively. Th e study was not performed according to theDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 30 of 68 American Wood PreserversS Association Standard and was not conducted for 30 or 45 days, but it provides adequate information for an envi ronmental fate assessment of TCMTB (MRID No. 441198-02). Table 13 below summarizes the degradat es of TCMTB formed during various fate studies.

Table 13 – Identification of Major Degradates of TCMTB

Degradate Name/ Abbrevia tion CAS# Structure

2-Mercaptobenzthiazole (MB) 149-30-4

2,2'-(dithiobis)benzothiazole (DBB) 120-78-5

2-benzothiazolol (BTOL) 934-34-9

Benzothiazol sulfonic acid (BTSA) Not found



### 4.1.2 Water Quality

TCMTB is not identified as a cau se of impairment for any wate r bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at the agencySs National Pesticides Cause of Impairment of Wa ters website (searched April 10, 2014). 4 In addition, no Total Maximum Daily Loads (TMD L) has been developed for TCMTB based on information provided at the agencySs National Pesticid e TMDL web site (searched April 10, 2014). 5 More information on impaired water bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/ . The agency invites submission of water quality data for this Pesticide Structure Activity Relationships.

4

. http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES N S

SH

N S

S S
N S

N S

OH

N S

SO 3 HDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 31 of 68 

## 4.2 Environmental Exposure Pathways
Aquatic organisms potentially at risk from expo sure to TCMTB or degradates include those inhabiting water bodies adjacent to or downstream from sources of down-the-drain discharges (e. g., waste water treatment plants), those exposed to leachate transported into the aquatic environment from applications of wood pres ervatives, and those inhabiting water bodies receiving runoff from fields planted with treated seed. Water bodies might include impounded bodies (e. g., ponds, lakes, reservoi rs) or flowing waterways (e. g., st reams, rivers). For uses in coastal areas, aquatic habitat al so includes marine ecosystems, including estuaries. Aquatic organisms likely to be acutely or chronically exposed include fi sh, invertebrates, and aquatic stages of amphibians. For aquatic animals, th e major route of exposure is considered to be uptake via the respiratory surface (gills) or th e integument from surface water that has TCMTB residues, including degradates. TCMTB exhibits minimal potential to bioconcentrate in fish (EPA 2006b and Appendix B). Aquatic plants also may be exposed. For aquatic plants, the major route of exposure is considered to be uptake from surface water.

Terrestrial organisms potentially at risk from exposure to TCMTB or its degradates include, but are not limited to, those consumi ng or contacting treated seed on the field, those drinking water (puddles) on the treated fields, or those contac ting, inhaling, or consuming dust occurring during mechanical planting of treated seed. In addi tion, TCMTB may move off-field through dust/drift during planting or runoff after planting and poten tially contact non-target seeds and plants.

All U.S. rice is produced in irrigated fields. Producers in th e United States can apply seed aerially in dry or flooded fields, or drill or broa dcast seed into dry fields. California producers seed primarily by air directly into flooded fields . Except for parts of southwest Louisiana and the Texas Gulf Coast, most producers in the South drill seed. Planting typi cally begins in early March in Texas and southwest Louisiana. The De lta plants the bulk of its crop in April, and California's crop is planted from late April throug h mid-May. Harvest begins in early or mid-July in Texas and southwest Louisiana. Peak harvest in the South is in September and early October, when the Delta harvests the bulk of its crop. So me producers in Texas and southwest Louisiana are able to reflood their fields after harvest and achieve a partia l second or "ratoon" crop from the stubble of the first. California typically begins harvest at the end of September and finishes by early November (USDA 2012 and EPA 2014).



## 4.3 Ecological Effects Assessment

4.3.1 Ecotoxicology Endpoints

4.3.1.1 Submitted Data Acute and chronic toxicity data from registra nt-submitted studies conducted in accordance with the 850 OCSPP Harmonized Test Guidelines will be used to evaluate the potential effects of TCMTB to plants and animals. All available ecotoxicity endpoints from studies submitted by registrants are tabulated in Appe ndix C. The most sensitive endpoi nts are used for assessing risk to each receptor group (Table 14). Some data also are available for one degradate (MB). In the absence of acute data for any of the degradates, they are assumed to be as toxic as the TGAI. Additional chronic data are anticipated to be needed for MB, a major degradate in the water column and aquatic sediment. Honey bee toxicity da ta are anticipated to be needed to assess risksDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 32 of 68 to beneficial insects from use of TCMTB to trea t wood. Acute toxicity data for the passerine are anticipated to be needed as passerines are often more sensit ive than upland game birds or waterfowl. Additional honey bee to xicity studies are anticipated to be necessary to address risks of TMCTB to pollinators.

Table 14 - Ecological Effects Endpoints for the Ecological Risk Assessment.

Receptor

Group Test Material Risk Scenario Toxicity Endpoint Reference

Freshwater fish TGAI Acute LC50 = 8.7 μg ai/L 41804201 Chronic NOAEC = 0.34 μg ai/L 42595901 2-MBT Acute LC50 = 730 μg ai/L 42232201

Freshwater invertebrates TGAI Acute EC50 = 22 μg ai/L 41838201 Chronic NOAEC = 0.89 μg ai/L 42559101 2-MBT Acute EC50 = 2900 μg ai/L 42226001

Estuarine/marine fish TGAI Acute LC50 = 60 μg ai/L 40363601 2-MBT Chronic Data gap -- Benthic invertebrates, freshwater and estuarine/marine 2-MBT Subchronic Data gap --

Estuarine/marine

invertebrates TGAI Acute EC50 = 13.9 μg ai/L 40363603

2-MBT Chronic Data gap --

Algae and Cyanobacteria TGAI EC 50 NOAEC EC50 = 2.7 μg ai/L NOAEC = 1.5 μg ai/L 4 8721501

Aquatic vascular plants TGAI EC 50 NOAEC EC50 = 430 μg ai/L NOAEC = 150 μg ai/L 44200901

Birds TGAI

Acute Bobwhite quail LD50 = 600 mg ai/kg 41780901

TGAI Passerine Data gap 2-MBT LD50 >2150 mg ai/kg 42267101

Mammals TGAI Acute LD50 = 750 mg ai/kg 41583801

Chronic NOAEC = 400 mg ai/kgdiet (no effects at any concentration) 41471401

Nontarget insects TGAI Acute and Chronic Data gaps (several studies anticipated to requested in registration review DCI) --

A registrant also submitted additiona l adverse effects information under a 1992 Submission of a Potential Adverse Effect 6(a)(2) (MRID 42405301). The information includes three extended abstracts published in the Proceedings of th e Seventeenth Annual Aquatic Toxicity Workshop (Chapman et al. 1991) and a summary of a thesis entitled The Effect of TCMTB on Juvenile CohoDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 33 of 68 Salmon (Oncorhynchus kisutch): Sublethal Toxicity Testing . These studies demonstrated that sublethal exposure to TCMTB caused gill damage and behavioral change s, including swimming performance, which could reduce the ability of fi sh to survive in the wild. Any relevant data from this submission will be addressed when the risk assessment is conducted.



## 4.4 Exposure Analysis Plan

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

Available OPP models will be used to determ ine the estimated environmental concentration (EECs) in the aquatic and terrestrial envi ronment. Resulting exposure estimates will be compared to the toxicity endpoints to determine if levels of concern are exceeded for each receptor group.



### 4.4.2 Screening Level Down-the-Drain Analysis The Down-the-Drain (DtD) module of E-FAST (E xposure and Fate Assessment Screening Tool) was used to determine the potential for aquatic organisms downstream of domestic wastewater treatment plants that receive discharges from end-use of 2-(thiocyanomethylthio) benzothiazole (TCMTB) to be exposed to TCMTB and its degrad ates. The results of the DtD module runs are expressed as number of days of exceedance of concentrations of concern (COC) for aquatic organisms. A detailed description of derivation of data for input paramete rs selected to run the DtD module and of the theoretical basis for this model is presented in Appendix D . A conservative assumption of no removal during wa stewater treatment was used in DtD model

runs.
The DtD analysis for TCMTB is intended to se rve two purposes: (1) to demonstrate the maximum WWTP influent volume of TCMTB that would trigger potential concerns for aquatic organisms exposed to TCMTB or its degradates downstream of domestic wastewater treatment plants and (2) to evaluate poten tial exposures based on the assu mptions that the total production volume of TCMTB enters domestic wastewater treatment plants. A key purpose of the DtD analysis for TCMTB is to determine the lowe st maximum annual WWTP influent volumes of TCMTB that would trigger poten tial concerns for aquatic organisms downstream of domestic WWTPs.

Table 15 presents results of a screening-leve l DtD analysis for TCMTB which is based on laboratory toxicity data for fr eshwater organisms. The DtD model predicted exceedances of COCs for acute and endangered aquatic organisms. In addition, a DtD analysis predicted that over 8000 kg/yr of TCMTB would have to enter domestic wastewater treatment plants to result in an exceedance for one day of the concentra tion of concern (COC) for endangered freshwater fish and invertebrates.

Table 15 - Summary of Screening Level Down-th e-Drain Analysis for Aquatic Organisms

WWTP Influent Volume Freshwater Fish Acute (COC = 4.35 ug/L) Fresh water Invertebrates (COC = 11 ug/L) Endangered species _fresh water fish (COC = 0.435 ug/L) Endangered species _fresh water invertebrates EndangeredspeciesAquatic plants (COC=1.5 ug/L)Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 34 of 68 (COC = 1.1 ug/L)

High-end Scenario – number of days COC exceeded per year

|1500000 kilograms/year 229 142 351 321 305

|8000 kilograms/year < 1 < 1 13 2 1

WWTP Influent Volume Freshwater Fish Chronic (COC = 0.34 ug/L) Chronic effects –Aquatic plantsNon listed (COC=430 ug/L) Chronic effects – Aquatic plants- listed (COC=150 ug/L) Aquatic plants (COC=2.7 ug/L)

|1500000 kilograms/year 356 < 1 day 4 267

|8000 kilograms/year 20 0 0 < 1

Average case Scenario – number of days COC exceeded per year

WWTP Influent Volume Freshwater Fish Acute (COC = 4.35 ug/L) Fresh water Invertebrates (COC = 11 ug/L) Endangered species _fresh water fish (COC = 0.435 ug/L) Endangered species _fresh water invertebrates (COC = 1.1 ug/L) EndangeredspeciesAquatic plants (COC=1.5 ug/L)

|1500000 kilograms/year 34 17 109 72 62

|8000 kilograms/year 0 < 2 < 1

WWTP Influent Volume Freshwater Fish Chronic (COC = 0.34 ug/L) Chronic effects –Aquatic plantsNon listed (COC=430 ug/L) Chronic effects – Aquatic plants- listed (COC=150 ug/L) Aquatic plants (COC=2.7 ug/L)

|1500000 kilograms/year 121 No exceedence No Exceedence 45

|8000 kilograms/year 2 No exceedence No exceedence No exceedence

This screening level analysis assumes that TCMT B is released to domestic wastewater treatment plants. Based on registered uses of TCMTB presen ted in Table 5 of this FWP, there are some uses, such as commercial and industrial cooling water systems and paper mill water systems, for which discharges may enter industrial WWTPs ra ther than domestic WWTPs prior to entering surface water. Different methods and tools fo r assessing potential exposures and associated ecological risks will be applied for these other types of uses. There is considerable uncertainty regarding th e amount of TCMTB that could be expected to enter domestic wastewater treatment plants. There is also uncertainty about the potential for exposure to aquatic organisms from TCMTB enteri ng industrial wastewater treatment plants as a result of industrial uses of MCMTB. The Agen cy does not have high quality data on the toxicity of TCMTB to activated sludge microorganisms in wa stewater treatment plants and does not have high quality data on biodegradati on of TCMTB during wastewater treatment. Consequently, theDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 35 of 68 agency anticipates needing the following data on TCMTB to fulfill data gaps regarding toxicity to activated sludge microorganisms and biodegrad ation of TCMTB during wastewater treatment:

1. Activated Sludge Respiration Inhibiti on (OECD 209) or Modified Activated Sludge Respiration Inhibition (OCSPP 850.6800); 2. Ready biodegradability test (835.3110) or one of three biodegradation in activated sludge simulation tests (835.3220; 835.3280; 835.3240) For more information on these tests, refer to Table 7.



## 4.5 Effects Analysis Plan

Along with the studies submitted by registrants, additional open litera ture studies will be identified through EPASs ECOTOXicology (ECOTOX) database. The ECOTOX database will be searched during the risk assessment phase and the data reviewed following the agencySs policy for reviewing public lit erature for use in assessing risks from pesticides. 6 Those ecotoxicity values found in the public literature to be more sensitive than those currently available or which satisfy an existing data gap(s) will be used during the risk assessment phase. ECOTOX was created and is maintained by the US EPA, Office of Research and Development, and the National Health and Environmental Ef fects Research Laboratory's Mid-Continent Ecology Division.



## 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 the 2006 RED for TC MTB, 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 secti on 408(p), TCMTB is subject to the endocrine screening part of the Endocrine Di sruptor Screening 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 mnaturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.n 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

6 http://www.epa.gov/pesticides/science/efed/policy_guidan ce/team_authors/endangered_s pecies_reregistration_work group/esa_evaluation_open_literature.htmDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 36 of 68 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 stage of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the agency must scr een all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. A second list of chemicals identified for EDSP screening was published on June 14, 2013 7 and includes some pesticides scheduled for registration review and chemicals found in water

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

For further information on the status of the ED SP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening batt ery, please visit our website. 8



## 6 Optional Label Changes

The agency invites any label amendments that c ould be considered to eliminate the anticipated need for EPA to require certain data, reduce the possibility that EPASs planned risk assessments overestimate risk due to reliance on conservative assumptions, and/or im prove label clarity.



## 7 Next Steps

A DCI will be developed regarding the data needs listed under the mRisk Assessments and Anticipated Data Needsn section of this docum ent. The agency expects to issue the DCI by March of 2016.

7 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.

8 http://www.epa.gov/endo/Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 37 of 68 

## 8 References

C. Smith D324013. TCMTB [2-(Thiocyanomethylth io)benzothiazole]: Second Revision of the Occupational and Residential Expos ure Assessment for the Reregistration Eligibility Decision Document. 7/27/2006

D. Smegal D322597. TCMTB Risk Assessment fo r the Reregistration Eligibility Decision (RED) Document 8/01/2006

EPA 2006a. Registration Eligibility Decision fo r 2-(Thiocyanomethylthio) benzothiazole (TCMTB), F. Sanders, Antimicrobials Division, August 1, 2006.

EPA. 2006b. Environmental fa te assessment of 2-(Thioc yanomethylthio) benzothiazole (TCMTB) for the Reregistration Eligib ility Decision (RED) Document. S. Gowda, Antimicrobials Division, February 16, 2006.

EPA, 2006c. Occupational and Residential Expos ure Assessment for 2-(Thiocyanomethylthio) benzothiazole TCMTB. DP 322615, S. Mo staghimi, Antimicrobials Division, April 19, 2006

EPA, 2014. Rice Production Practices in the United Stat es and Use of Cyhalofop-butyl for Weed Control in Rice Production (DP # 420989) . Memo from Biological and Economic Analysis Division (7503P) to Pesticide Re-evalu ation Division (7508P); August 20, 2014. U.S. Environm ental Protection Agency, Office of Prevention, Pesticides and Toxic Substa nces, Office of Pesticide Programs, Biological and Economic Analys is Division, Washington, DC.

Kline, 2005. Specialty Biocides North Ameri ca 2004-2005, Volume II: United States, Kline and Company, Inc.

Manninen, A., Auriola S, Vartiainen M., Leisiv uori J., Turunen, T., Pasanen M. 1996. Determination of urinary 2-mercaptobenzothiazole (2-MBT), the main metabolite of 2-(thiocyanomethylthio)benzothiazo le (TCMTB) in humans and rats.

S. Ary D322617. TCMTB. Summary of Analyti cal Chemistry and Residue Data for the Reregistration Eligibility Deci sion (RED) Document. 2/28/2006/

S. Ary D324018. TCMTB. Acute and Chronic Dietary Exposure Assessments for the Reregistration Eligibility Decision (RED) Document.2/28/2006United States Department of Agriculture (USDA). 2012. Rice: Background, U.S. Rice Production. http://www.ers.usda.gov/topics /crops/rice/background.aspx (Date Accessed: July 30, 2014). Economic Research Service. Washington, DC. USEPA, 2014. Rice Production Practices in the Unite d States and Use of Cyhalofop-butyl for Weed Control in Rice Production (DP # 420989) . Memo from Biological and Economic Analysis Division (7503P) to Pesticide Re-evalu ation Division (7508P); August 20, 2014. U.S. Environm ental Protection Agency, Office ofDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 38 of 68 Prevention, Pesticides and Toxic Substa nces, Office of Pesticide Programs, Biological and Economic Analys is Division, Washington, DC.

T. Bloem D418804. TCMTB. Review of Cott on Metabolism Study Submitted in Response to Deficiencies Identified in the TCMTB ((2-benzothiazolylthio)methyl thiocyanate) Reregistra tion Eligibility Decision (RED) Document. 8/26/2014

United States Department of Agriculture (USDA). 2012. Rice: Background, U.S. Rice Production. http://www.ers.usda.gov/topics /crops/rice/background.aspx (Date Accessed: July 30, 2014). Economic Research Service. Washington, DC.

42405301. Chapman, P., F. Bishay, E. Power, K. Hall, L. Harding, D. McLeay, M. Nassichuk, and W. Knapp (eds). 1991. Proc. 17th Annual Aquatic Toxicity Workshop, November 5-7, 1990, Vancouver, B.C. Canadian Tech. Rep. Fisheries and Aquatic Sci. No. 1774 (vol 1).

00153800 Schulz, M. (1985) Delayed Contact Hype rsensitivity (Buehler Technique) of TCMTB: Intox Sample No. 513: Protoc ol No. BUC-AT-046. Unpublished study prepared by Intox Labor atories, Inc. 20 p.

00154295 Goad, P. (1985) Teratogenicity Study of TCMTB in Rats: Report: Project BUCTR-001. Unpublished study prepared by Intox Labora- tories. 270 p.

00165518 Bonner, G. (1986) Evaluation of Ot her Genotoxic Effects TCMTB (EPA Reg. No.:1448-29): In the Rat Primary Hepa tocyte Unscheduled DNA Synthesis Assay: HBC Project No. 20991. Unpublis hed study prepared by Hazleton Biotechnologies Company. 21 p.

00165520 Bonner, G. (1986) Evaluation for Struct ural Chromosomal Aberration of TCMTB (EPA Reg. No.:1448-29): Clastogenic Evaluation in the in vivo Mouse Micronucleus Assay: HBC Project No. 20996. Unpublished study prepared by Hazleton Biotechnologies Co. 23 p.

40075102 Adam, G. (1986) TCMTB - A Teratology Study in Rabbits: Final Re- port: Project No. WIL-94014. Unpublished st udy prepared by WIL Research Laboratories, Inc. 167 p.

40075102 Adam, G. (1986) TCMTB - A Teratology Study in Rabbits: Final Re- port: Project No. WIL-94014. Unpublished st udy prepared by WIL Research Laboratories, Inc. 167 p.

40884801 Cameron, B.; Scott, G. (1987) The Metabolism of 2-(Thiocyanomethylthio)benzothiazole (TCMTB) in the Rat: Project ID: IRI 135365. Unpublished study prepared by Inveresk Resear ch International Limited. 10 p.

41342201 Goburdhun, R.; Greenough, R. (1988) 2-(Thi ocyanomethylthio) Benzothiazole (TCMTB) 52 Week Dietary Toxicity Study in Dogs: Lab Project No. 635605;Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 39 of 68 Report No. 5646. Unpublished study prepared by Inveresk Research International. 160 p.

41386101 Lawlor, T.; Respess, C. (1990) Mu tagenicity Test on TCMTB in the Salmonella/Mammalian-microsome Reverse Mutation Assay (Ames Test) with Confirmatory Assay: Final Report: Lab Project I.D.: 110277-0-401R. Unpublished study prepared by Hazleton Laboratories America, Inc. 32 p.

41471401 Hazelden, K.; Wilson, J. (1988) TCMT B Two Generation Reproduction Study in Rats: Report No. 5168: IRI Project No. 435334. Unpublished study prepared by Inveresk Research In ternational. 156 p.

41515401 Hazleton-Institut Francais de Toxico logie (1990) TCMTB Technical Grade: Acute Dermal Median Lethal Do se: Lab Project Number: 410211. 48 p.

41529701 Everett, D.; Hudson, P.; Atkinson, C.; et al. (1988) 2-(Thiocyano- methylthio) Benzothiazole (TCMTB): 104 Week Dietary Carcino- genicity Study in Rats with 52 Week Interim Kill (Results After 52 Weeks): Lab Project Number: 435313: 5558. Unpublished study prepared by Invere sk Research International. 247 p.

41570301 Finch, J. (1990) TCMTB--104 Week Diet ary Carcinogenicity Study in Rats with 52 Week Interim Kill: Lab Project Number: 435313. Un- published study prepared by Inveresk Research International, Ltd. 8 p.

41583701 Rush, R. (1990) Primary Skin Irritati on Study in Rabbits with TCMTB -80 (...): Lab Project Number: 3138.61. Unpublished study pre- pared by Springborn Laboratories, Inc. 20 p.

41583801 Rush, R. (1990) Acute Oral Toxicity Study in Rats with TCMTB-80 (.. .): Lab Project Number: 3138.59. Unpublishe d study prepared by Springborn Laboratories, Inc. 63 p.

41640601 Terrill, J. (1988) Acute Inhalation Toxi city Study with TCMTB in the Rat: Lab Project Number: 197/188. Unpublished study pre- pared by Hazl eton Laboratories America, Inc. 53 p.

41655801 Siglin, J. (1990) 21-Day Dermal Toxici ty Study in Rats with TCMTB- 80: Final Report: Lab Project Number: 3138.53. Unpublished stu- dy prepared by Springborn Laboratories, Inc. 274 p.

42116301 Everett, D.; Perry, C.; Atkinson, C.; et al. (1991) 2-(Thiocyano- methylthio) Benzothiazole (TCMTB): 104 Week Dietary Carcino- genicity Study in Rats with 52 Week Interim Kill (Results Afte r 104 Weeks): Supplement: Lab Project Number: 435313. Unpublished study prepared by Inveresk Research International. 1160 p.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 40 of 68 42349201 Karcher, R.; Siglin, J.; Becci, P. (198 6) Delayed Contact Hypersensitivity Study in Guinea Pigs with HPMTS: Lab Project Number: 3138.7. Unpublished study prepared by Springborn Institute for Bioresearch, Inc. 55 p.

42383001 Everett, D.; Atkinson, C.; Heath, J. et al. (1990) 2-(Thiocyanomethylthio) Benzothiazole 104 Week Dietary Carcinoge nicity Study in Mice: ?Final Report|: Lab Project Number: 435329: 7516. Unpublis hed study prepared by Inveresk Research Intl. 726 p.

42418501 Blasberg, J.W., S.L. Hicks and L.S. Stuerman. 1992. Uptake, Depuration, and Bioconcentration of 14 C-TCMTB by Bluegill Sunfish Leopmis macrochirus

. Unpublished data. Conducted by ABC Laboratories, Inc. for Buckman Laboratories International, Inc.

43112801 Atkins, C.; Perry, C.; Finch, J. (1987) 2-(Thiocyanomethylthio) Benzothiazole (TCMTB): 13 Week Dietary Dose Range Finding Study in Rats: Lab Project Number: IRI 435528: 3930. Unpublished study prepared by Inveresk Research International. 79 p.

46947214 Bernardo, W. (2000) 90 Day Dermal Toxicity Study Synopsis and Toxicity Category Recommendation Technical Grade Ac tive Ingredient TCMTB. Project Number: B/0456/9. Unpublished study pr epared by Opus Prima S.A. 39 p.

46947216 Bernardo, W. (1999) Bacterial Revers e Mutation Test Synopsis and Toxicity Category Recommendation Technical Grade Active Ingredient TCMTB. Project Number: B/0459/9. Unpublished study pr epared by Opus Prima S.A. 12 p.

46947217 Richiello, G. (2005) "In Vitro" Mammalian Cell Gene Mutation Test Study Synopsis and Toxicity Category Reco mmendation Technical Grade Active Ingredient TCMTB. Project Number : B/0459/9. Unpublished study prepared by Opus Prima S.A. 10 p.

46947218 Richiello, G. (2005) Un scheduled DNA Synthesis in Ma mmalian Cells in Culture Test Synopsis and Toxicity Category Recommendation Technical Grade Active Ingredient TCMTB. Project Number : B/0459/9. Unpublished study prepared by Opus Prima S.A. 10 p.

92179026 Rao, G. (1990) Buckman Labs Inc Phase 3 Reformat of MRID 00050882 and Related MRIDs 00031588. 90 Day Subchronic Oral Toxicity: Study of TCMTB in Rats: Study No. 79003. Prepared by Ra ltech Scientific Services. 438 p.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 41 of 68 

# Appendix A Toxicology Profile

Acute Toxicity for Product Labeling

The data base for acute toxicity is considered co mplete. No additional studies are expected to be required at this time. TCMTB exhibits low acute or al and dermal toxicity (toxicity category III). However, it is highly irritating to the eyes and skin (toxicity ca tegory I and II, re spectively)) and is also considered to be highl y toxic via the inhalation route of exposure (toxicity category I). TCMTB is a dermal sensitizer. The acute toxici ty data on the TCMTB Te chnical (80% ai), or Busan 72 (containing 60% ai) are summarized below in Table A1.

Table A1 j Acute Toxicity Studies for TCMTB

Guideline No./ Study Type MRID No. Results Toxicity Category 870.1100/ Acute oral toxicity 41583801 LD 50 = 750 mg/kg (M+F); 80% ai III

870.1200/ Acute dermal toxicity 41515401 LD 50 > 2000 mg/kg (M+F); 80% ai III

870.1300/ Acute inhalation toxicity 41640601 LC 50 =0.07 mg/L; 80% ai I

870.2400/ Acute eye irritation Acc No. 111991 Diluted Busan 72 (60 % ai): primary irritation score (PIS)=2/110 (slight conjunctival redness, no corneal opacity); undiluted Busan 72 (60% ai) PIS=34/110 (blanched conjunctivae, chemosis, corneal opacity not reversible by day 7) I

870.2500/ Acute dermal irritation 41583701 primary irritation index=7.42 with severe erythema and edema observed at 72 hours; 80% ai II

870.2600/ Skin sensitization MRID 00153800, 42349201 Busan 74 (80% ai) caused delayed contact hypersensitivity in guinea pigs when induce d and challenged by a 40% w/v aqueous concentration of active ingredient. Sensitizer.

N/A=Not available 

## Subchronic Toxicity

The data base for subchronic toxicity is consid ered adequate for risk assessment purposes. Although the subchronic rodent studi es are unacceptable, there are chronic studies available to fulfill the guideline requirements. In addition to the studies listed below, the agency is reviewing a 90 day dermal study received since the 2006 RED (46947214).

Following repeat oral exposures to rodents, TCMT B caused increased incidence of mild to severe stomach lesions characterized by inflammati on, hyperplasia, necrosis, and ulceration. Inflammatory cells infiltration a nd edema were also noted at a lo w incidence. TCMTB resulted in decreased body weight gains (78 to 84% of contro l), food consumption (87-95% of control) and food efficiency. In a 21-day rat dermal toxicity study, TCMTB produced dose-dependant dermalDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 42 of 68 irritation in all dose groups beginni ng on treatment days 3-4, which progr essed to eschar formation. Rats in the mid and high dose group had ulcers, hemorrhages and chronic dermatitis. Decreased body weight gain, food consumption, and hematol ogical (changes in hem oglobin, hematocrit, and segmented neutrophils) and clini cal chemistry changes (blood urea nitrogen, glucose, globulins, and elevated serum aspartate aminotransferase (A ST) were also noted. However, the clinical chemistry changes did not correspond to any trea tment-related findings in the liver or kidney.

870.3100 90-Day Oral Toxicity - Rat

In a 13 week range finding study (MRID 43112801), TCMTB (81.56% ai, Batch 1517 MRID 46698604, 92179001) was administered to Sprague-Dawley ra ts (n=10/sex/dose) in the diet at dose levels of 0, 10, 30, 70 or 100 mg/kg/ day (actual doses: 10.2, 31, 70 and 100 mg TCMTB/kg/day for males and 10.3, 31, 72 and 99 mgTCMTB/kg/day for females using food consumption data). These doses are equiva lent to 8.3/8.4 (M/F), 24.5, 57/59 (M/F), 80.8/81.6 (M/F) mg ai/kg/day, respectively when considering the purity of the test substance as 81.56% ai. This study examined limited parameters.

Systemic toxicity was noted at 30 mg/kg/day (2 4.5 mg ai/kg/day) and above in the form of increased incidence of squamous epithelial hype rplasia of the stomach. There were also treatment related decreases in body weight gains (78 to 84% of control), food consumption (87- 95% of control) and food effi ciency (89-94% of control) in both sexes of to 70 and 100 mgTCMTB/kg/day (57/59 (M/F) and 80.8/82.6 (M/F) mg ai/kg/day). The LOAEL for systemic toxicity is 30 mg TCMTB/kg/da y (24.5 mg ai/kg/day) and the NOA EL for systemic toxicity is 10 mg TCMTB/kg/day (8.3.8.4 mg ai/ kg/day) based on increased inci dences of stomach lesions.

This 90-day oral toxic ity study in the rat is UNACCEPTABLE-GUIDELINE and does not satisfy the guideline requirement for a subc hronic (90-day) oral toxicity study OPPTS 870.3100 in the rat because is was only a range finding st udy, and based on major deficiencies (stability, diet concentrations and homoge neity were not measured, and he matology and clinical chemistry parameters were not measured). This study can not be upgraded. Although this study is unacceptable, there are chronic studies availabl e to fulfill the guideline requirements. No additional oral toxicity data are antici pated to be required at this time.

870.3100 90-Day Oral Toxicity - Rat

In a 90-day study (MRID 92179026), TCMTB (Lot 9-3573; approximately 80% as supplied by the registrant via email correspondence) wa s administered to Sprague-Dawley rats (n=30/sex/dose) in the diet at dose levels of 0, 333, 500 and 750 ppm for 90 days. Dietary doses were approximately 0, 16.7, 25, 37.5 mgTCMTB/kg/da y, which is equivale nt to 0, 13.4, 20 and 30 mg ai/kg/day, respectively based on a purit y of approximately 80% ai. (as supplied by the registrant).

There were no treatment-related effects on any of the parameters measured except histopathology. Mild inflammatory changes were found in the gastric mucosa of males in theDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 43 of 68 high dose group. Mild to severe changes in th e stomach, including inflammation, necrosis and ulceration, were found in the females in this group. Females in the mid-dose group had a low incidence of inflammatory cells infiltration (5% vs . 0% in the control) a nd edema (10% vs. 0% in the control).

The NOAEL is 500 ppm (25 mg TCMTB/kg/day or 20 mg ai/kg/day). The LOAEL is 750 ppm (37.5 mg TCMTB/kg/day or 30 mg ai/kg/day). The Maximum Tolerated Dose (MTD) in males is slightly higher than 750 ppm (based on histopathology findings); females is slightly lower than 750 ppm (based on incidence and severity of histopathology findings in the stomach).

This 90-day oral toxic ity study in the rat is UNACCEPTABLE-GUIDELINE and does not satisfy the guideline requirement for a subc hronic (90-day) oral toxicity study OPPTS 870.3100 in the rat because the percent recovery of TCMTB in the diets was low (81, 82 and 84% for the low, mid- and high dose groups, respectively), and ophthalmosc opic examinations were not done. The approximate purity of 80% ai was su bmitted in late 2005 by the registrant. Although this study is unacceptable, there are chronic studies available to fulfill the guideline requirements. No additional data are antic ipated to be required at this time.

870.3200 21-Day Dermal Toxicity - Rat

Executive Summary: In a dermal toxi city study (MRID 41655801), TCMTB (82.33% a.i. Lot OB-8483 via fax submission dated December 8, 2005) was applied to the skin of SpragueDawley rats (5/sex/group ) at dose levels of 0, 25, 100, or 250 mg/kg/day for 21 days (6 hours/day). These doses are equivalent to 0, 20.6, 82.3 and 206 mg ai/kg/day. TCMTB produced slight to moderate dermal irritation in all dose groups be ginning on treatment days 3-4. Dermal irritation was dose-dependent and progressed to eschar formation in 2 rats (1 male and 1 female) in the low dose group in all rats of the mid and high dose groups . Blanching occurred in all rats of the high dose group and in all females and 3/5 males in the mid dose group. Decreased body weight gain was noted at the mid and high dose groups of male rats. Statistically significant changes in hemoglobin, hematocrit, and segmented neutrophils we re observed in male and female rats of the high dose level. Several clinical chemistry parameters were signifi cantly increased in high dose males and females (blood urea nitrogen, glucose a nd globulins); while high dose females also had elevated serum aspartate aminotransferase (AST). However, the clinical chemistry changes did not correspond to any treatment-relate d findings in the liver or kidney.

The Systemic NOAEL = 20.6 mg ai/kg/day, and the Systemic LOAEL = 82.3 mg ai/kg/day, based on decreased body weight gain, food consumption, and hematological and clinical chemistry changes. A Dermal NOAEL was not identified. The Dermal L OAEL is 20.6 mg ai/kg/day based on dose-dependent irritation which progressed to eschar formati on in 2 rats of the low dose group and in all rats of th e mid- and high-dose groups. Mid- a nd high-dose groups ex hibited ulcers, hemorrhages and chronic dermatitis.

Based on the recent submission of purity informa tion in 2005, this 21-day dermal toxicity study in the rat can be upgraded to ACCEPTABLE-GUIDELINE , and satisfies the guideline requirement for a subchronic dermal toxicity study OPPTS 870.3200 in the rat. No additional studies are anticipated to be required at this time.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 44 of 68 

## Developmental Toxicity

The data base for prenatal developmental toxicity is considered complete. Developmental toxicity studies were available in both the rat and rabbit fo r TCMTB. No additional studies are anticipated to be required at this time. Rabbits appear to be more sensitive to the toxicity of TCMTB than rats. In rabbits, the maternal NOAEL and LOAEL were 16 and 32 mg ai/kg/day, respectively. In rats, the maternal NOAEL and LOAEL were 21 a nd 64 mg ai/kg/day. No developmental effects were noted in the rabbit at the highest dose tested (32 mg ai/kg/day). Howe ver, in the rat adverse developmental effects including increased fe tal and litter incidence of fused/wavy ribs, rudimentary cervical, thoracic and lu mbar ribs and increased incide nce of sternebrae and pelvic girdle anomalies were noted at doses of 105 mg ai/kg/day, which wa s maternally toxic. Thus, the Agency concludes that these studies show no ev idence of primary developmental toxicity of TCMTB, which is consistent with the previous conclusion of th e Health Effects DivisionSs RfD Peer Review committee (September 29, 1994; document # 011302).

870.3700a Prenatal Developmental Toxicity Study - Rat

In a prenatal developmental toxicity study (MRID 00154295); TCMTB (83.6% a.i. Lot 511230, MRID 46698601), was administered to 5 groups of 29 mated female Sprague-Dawley rats per group by oral gavage using technical TCMTB dissolv ed in corn oil/ 1% Tw een 80 at doses of 0, 25.1, 76.5, and 125.5 mg/kg/day from gest ation days 6 through 15. Thes e doses are equivalent to 0, 21, 64 and 105 mg ai/kg/day, respectively. Maternal toxicity was evident at the 64 mg ai/kg/day (76.5 mg TCMTB/kg/day) dose level as ventra l alopecia, rough coat, dyspnea/wheezing, oral discharge, nasal discharge, di arrhea/loose stool, urine staining, piloerection, and hunched gait. Developmental toxicity was evident at the 105 mg ai/kg/day (125.5 mg TC MTB/kg/day) dose level in the form of increased fetal and litter inci dence of fused/wavy ribs , rudimentary cervical, thoracic, and lumbar ribs, and in creased number of sternebrae a nd pelvic girdle anomalies.

The Maternal NOAEL = 21 mg ai/kg/day (25.1 mg TCMTB/kg/day), based on observations of clinical toxicity at 64 mg ai/kg/day (76.5 mgTCMTB/kg/day) (LOAEL). The Developmental NOAEL = 64 mg ai/kg/day (76.5 mg TCMTB/kg/day), based on increase d fetal and litter incidence of skeletal anomalies.

This developmental toxicity study in the rat is classified as A CCEPTABLE-GUIDELINE and satisfies the requirement (OPPTS 870.3700) for a developmental toxi city study in the rodent. No additional studies are anticipated to be required at this time.

870.3700b Prenatal Developmenta l Toxicity Study - Rabbit

In a prenatal developmental toxicity (t eratology) study (MRID 40075102), TCMTB (81.0 % a.i ., Lot 5-13002, MRID 46698602) was orally dosed to presumed pregnant rabbits at dose levels of 0, 10, 20 and 40 mg/kg/day (20 rabbits/group) during gestation days 6-19 inclusive. These doses are equivalent to 0, 8, 16, and 32 mg ai/ kg/day, which were verifi ed by the registrant.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 45 of 68 Maternal toxicity was evidenced by decreased body weight gain and food consumption in the 32 mg ai/kg/day dose group. Statis tically significant (p>0.01) body weight loss was noted in the high dose group on gestation days 6-12, 6-19 and 19-29. Mean food consumption was significantly reduced for the high dose group during gestation days 6-12 and 6-19. One high dose and two mid-dose group rabbits died during the study. However, only the high dose death, which occurred on gestation day 18, was consider ed treatment related based on corroded gastric mucosa and reddened duodenal mucosa. There were no clinical signs of toxicity in any dose level during the study. Five dams a borted their litters prio r to scheduled sacrific e (1 control, 2 in the low dose group and 2 in the mid-dose group). No animals in the high dose group aborted, therefore, the abortions occurri ng in the lower dose groups were considered to be spontaneous, which is not uncommon in rabbits . The Maternal Toxicity NOAEL is 16 mg ai/kg/day and the Maternal Toxicity LOAEL is 32 mg ai /kg/da y based on decreased body weight gain and food consumption.

No statistically si gnificant or treatment-re lated changes were noted in any treatment group for deaths/resorptions, altered growth, devel opmental anomalies or malformations. The Developmental Toxicity LOAEL is greater th an 32 mg ai/kg/day and the Developmental Toxicity NOAEL is greater than or equal to 32 mg ai/kg/day.

This study is classified as ACCEPTABLE-GUIDELINE and satisfies the guideline requirement (§870.3700) for a developmental toxici ty (teratology) study in rabbits . No additional studies are anticipated to be required at this time.



## Reproductive Toxicity

The data base for reproductive toxicity is c onsidered complete. No additional studies are required at this time. The available data show ed that TCMTB did not cause reproductive effects in rats.

In a 2-generation reproduction toxicity st udy (MRID 41471401), TCMTB (81.6% ai, Batch 1517; MRID 92179011, 46698604) was administered to Sprague Dawley CD outbred albino rats from Charles River UK Ltd. in the diet at dose le vels of 0, 25, 100, or 400 ppm (2.4, 9.6, and 38.4 mg/kg/day for males and 3.0, 11.7, and 45.5 mg/kg/day for females for the 25, 100, and 400 ppm groups, respectively) for 2 generations with 1 litter in the first generation and 2 litters in the second generation. No treatment related effects were noted on reproductive parameters examined in this study. Slight, statistically signi ficant effects were noted in m ean body weight in the high dose offspring in the second mating (F 2B) around lactation day 21 (approxi mately 88% of control pups). This must be considered as systemic toxicity as the litters began with relatively equal mean body weights and around lactation day 14, the pups began to consume diet while continuing to nurse, and thus mostly likely received more than 400 ppm TCMTB. Mean pup weight was not significantly reduced at days 7 or 14 in the F2B pups, and there were no consistent effects on pup weight in the F0 and F1a generation pups. Thus, the Agency believes this finding in the F2B pups on day 21 is of questionable toxi cological significance.

The parental/systemic NOAEL = 400 ppm (38.4/45.5 mg /kg/day [males/females]) and theDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 46 of 68 parental/systemic LOAEL > 400 pp m (> 38.4/45.5 mg /kg/day [males/females]). The offspring NOAEL is 400 ppm (HDT) and the offspring LOA EL > 400 ppm. The Reproductive toxicity NOAEL > 400ppm and the Reproductive toxicity LOAEL > 400 ppm.

This study is classified as ACCEPTABLE-GUIDELINE and satisfies the guideline requirement for a 2-generation reproductive st udy (§870.3800; OECD 416) in rats

Consistent with both the RfD Peer ReviewSs conclusion and that of the California Environmental Protection AgencySs summary of TCMTB (Feb ruary 22, 2001), there was no evidence of reproductive toxicity of TCMTB. No additional studies are anticipated to be required as this time.



## Chronic Toxicity

The data base for chronic toxicity is consider ed complete, and no additi onal studies are required at this time.

In a chronic toxicity study (MRID 41342201), te chnical TCMTB (81.6% ai, Batch 1517; MRID 92179008, 46698604) was administered to male and fe male beagle dogs at dose levels of 0, 100ppm (3.8 mg/kg/day in males; 4.0 mg/kg/day in females), 300pp m (11.7 mg/kg/day in males; 11.2 mg/kg/day in females), and 1000ppm (38.8 mg/kg/day in males; 43.2 mg/kg/day in females). Decreased body weight and body weight gain were observed in male dogs at the 100 ppm dose level for weeks 0-13 of the study, and overall body weight and weight gain were decreased greater than 10% in both male a nd female dogs at the 1000 ppm dose level. Hematological effects include significant decr eases in circulating white blood cells and monocytes in male dogs at all dose levels test ed, while effects on hematology in female dogs were limited. Plasma ALT was significantly decr eased in both sexes in a dose-related manner at all dose levels in both male and female dogs for the duration of the study. Decreased weight of the lung, thymus, and spleen were observed in male dogs at the 1000 ppm dose level, while decreased spleen, thymus, and uterine weight we re observed in female dogs. Involution of the thymus was the main histologic finding, and the seve rity of this lesion app eared to increase with increasing dose in both sexes. The Systemic NOAEL < 100 ppm (males and females). The Systemic LOAEL = 100 ppm [3.8 mg /kg/day for males; 4.0 mg /kg/day for females], based on decreased body weight gain, white blood cells, monocytes and plas ma ALT in males; decreased plasma ALT and uterine weight in females.

This chronic study in the dog is classified as ACCEPTABLE- NON-GUIDELINE and does not satisfy the guideline requirement for a chronic oral study (OPPTS §870.4100, OECD 452) in dogs because a systemic NOAEL was not achieved. Howe ver, this study is sc ientifically sound and adequate for use in risk assessment. No additional data are anticipated to be required at this time.



## Carcinogenicity

The data base for carcinogenicity is consid ered complete, and no additional studies are anticipated to be required at this time. TCMTB produced an increa se in testicular interstitial adenomas in male rats and thyroid C-cell adenomas in female rats.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 47 of 68 Combined Chronic Toxicity/Carcinogenicity Study in Rats (MRID No.: 42116301; 41529701; 41570301)

In a combined chronic/carcinogen icity study (MRID 42116301; 41529701; 41570301), TCMTB (81.6% ai purity, MRID 46698604) was administered to Sprague Dawley rats of both sexes (50/sex/dose, main group; and 20/sex/dose, inter im kill group) for a period of up to 104 weeks in the diet at dose levels of 0, 2, 8, or 20 mg/kg/day. Mortality was variable with survival rates of 80-100% in the interim kill group and 38-82% in the carcinogenicity group. No treatment-related clinical signs of toxici ty were noted during the study. No dos e-related or signifi cant effects were noted in the interim kill group. The only significant reduction in body weight gains occurred in the 20 mg/kg/day males at week 80, and these do not appear to be treatment-related. No doserelated or significant effects were noted in the food consumption of either the interim kill group or the carcinogenicity group. A dose-related decrease in plat elets was noted in all treated females at week 104. All other changes in hematology parameters were not cons idered to be toxicologically significant. No changes in the clinical chemistry parameters were considered to be biologi cally significant due to the lack of a doseÇresponse relationship. No treatmentÇrelated changes were noted in the organ weights of the interim kill group, but an increasing trend was noted in the female absolute liver weights in all treatment groups. Since a do se response relationship wa s not present, it was not considered to be biologically significant. Terminal organ wei ghts were not reported. Only one finding displayed a dose-response relations hip in the microscopic pathology, interstitial cell tumors in the testes. The tumor incidenc es were control group 4/50, low dose 5/50, mid dose 13/50 and the high dose with 14/50. The mid an d high doses were significantly different (p<0.05) from the controls. Additi onally, the incidence of thyroi d C-cell adenomas was increased in female rats of the high dose group, as compar ed to controls. The incidence of this lesion was 6/49, 4/49, 7/48 and 13/50 for the control, low, mid and high dose groups, respectively. Thus, TCMTB appears to be carcinogenic inducing the formation of inters titial cell tumors in the testes and thyroid C-cell adenom as in female rats. Although the current study did not ap pear to test to high enough doses to produce systemic toxicity, on the basis of results from other t oxicity studies (noted below) as cited in the Cancer Peer Review document, this study is classified as ACCEPTABLE-GUIDELINE and satisfies the OPPTS 870.4300 test guideline. No additional studies are an ticipated to be required at this time.

Discussion of Tumor Data

Two findings displayed dose-respon se relationships in the micros copic pathology, in terstitial cell tumors in the testes and thyroid C-cell adenomas in female rats. Male rats had a significant doserelated increasing trend, as well as significant differences in the pair-wise comparisons of the 8 and 20 mg/kg/day dose groups with the controls , for testicular inte rstitial cell tumors.

Female rats had significant dose- related increasing trends, and signi ficant differences in the pairwise comparisons of the 20 mg/kg/ day dose group with th e controls for thyroid C-cell adenomas and adenomas and/or carcinomas combined; howe ver, only adenomas were present in treated groups (the control group had th e single carcinoma noted). Alt hough there were no significantDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 48 of 68 differences in the pair-wise comparisons of the dosed groups with the controls, female rats did have a significant increas ing trend in thyroid C-ce ll hyperplasia at p < 0.01.

Adequacy of the Dose Levels Tested

The statistical evaluation of mortality indi cated no significant incr emental changes with increasing doses of TCMTB in male rats. Female rats showed a signific ant decreasing trend in mortality with increasin g doses of TCMTB.

No treatment-related clinical signs of toxicity were noted during the study. The only significant reduction in body weight gains occurred in the 20 mg/kg/day males at week 80, and this did not appear to be treatment-related. No dose-related or significant effects were noted in the food consumption.

A dose-related decrease in plat elets was noted in all treated females at week 104. All other changes in hematology parameters were not consid ered to be toxicologically significant. No changes in the clinical chemistry parameters were considered to be biologi cally significant. An increasing trend was noted in the female absolute liver weights in all treatment groups; however, since a dose response relationship was not present it was not cons idered to be biologically significant.

The systemic toxicity observed in this study in male and female rats was minimal and there were no major differences between the treated and cont rol groups. However, data obtained from two subchronic feeding studies in rats (the 13 week range finding study, MRID# 43112801 and the 90 day study in rats, MRID# 92179026) i ndicate that toxic effects (d ecreased body weight gain and increased incidence of squamous epithelial hyperplasia of the st omach) were observed at the dose level of 30 mg/kg/day (a dose sli ghtly higher than the HDT in th is study). The Systemic LOEL is greater than 20 mg/kg/day and the NOEL is equal to or greater than 20 mg/kg/day. The study is considered in combination with the 13 week range finding study (MRID# 43112801) and the 90 day study in rats (MRID# 92179026). Based on this information, the dose levels used in the chronic/carcinogenicity study in ra ts (MRID#Ss 42116301, 41529701, and 41570301) were adequate for testing for the carcinogenic potential of TCMTB.

Carcinogenicity Study in Mice (MRID No.: 42383001)

In a carcinogenicity study (MRID 42383001), TCMTB (81.6% ai, batch 1517/Lot number 6- 14285, MRID 46698604) was administered to groups of CD-1 mice ( 50/sex) in the diet at concentrations calculated to gi ve dose levels of 0, 15, 50, or 150 mg/kg/day for 2 years. These doses are equivalent to 0, 4, 41 and 122 mg ai/ kg/day, respectively. No carcinogenic potential was seen. Body weights were significantly reduced in high-dose males and high dose females compared to controls. Weight ga ins in high dose males and female s were approximately 25% lower than controls at 78 weeks. Cumulative weight gain was reduced 36% and 28% for high dose males and females, respectively at week 104. There wa s no effect on food consumption in this study. None of the gross findings were remarkable. An increase in focal and diffuse hyperplasia of the duodenal mucosa was seen microscopically in ma les receiving 150 mg/kg/day: the incidence was 10/42 compared to 1/41 in cont rols (p<0.01). A nonsignificant in crease was seen for mucosalDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 49 of 68 hyperplasia of the duodenum in high- dose females (8/45 compared to 4/46 in controls). No other pathologic findings were consider ed treatment related. The Systemic NOAEL is determined to be 50 mg/kg/day (41 mg ai/kg/day), and the Systemic LOAEL is determined to be 150 mg/kg/day (122 mg ai/kg/day), based on histologic changes in the d uodenum of high dose males and decreased weight gain in both sexes at the high dose.

This carcinogenicity study in the mouse is ACCEPTABLE-GUIDELINE and satisfies the guideline requirement for a carcinogenicity study (OPPTS 870.4200; OECD 451). No additional data are anticipated to be required at this time.

Discussion of Tumor Data

There were no compound-related tu mors observed in male or fema le mice. All tissues were examined.

Adequacy of the Dose Levels Tested

The statistical evaluation of mortality indi cated no significant incr emental changes with increasing doses of TCMTB in male mice. Female mice showed a signifi cant decreasing trend in mortality with increasin g doses of TCMTB.

Body weights were significantly reduced in high -dose males and high-dose females as compared to controls. Weight gains in high-dose groups were about 88% of control in males and 97% of control in females at 13 weeks; however at 80 week s the weight gains were 67% of control in the males and 78% of control in the females and cumulative mean gains for the entire treatment period (weeks 0-104) were 64% and 72% of the c ontrols for the high-dose males and females, respectively. No marked effects on food cons umption were observed. None of the gross findings were remarkable. Based on the histol ogic changes in the duodenum in high-dose males and the decreased weight gain in both sexes at the high-dose, the system ic toxicity LOAEL is considered to be 150 mg/kg/day (122 mg ai/ kg/day) and the systemic toxicity NOAEL is 50 mg/kg/day (41 mg ai/kg/day).

The high dose tested (150 mg/kg/day) is consider ed to be an adequate dose for assessing the carcinogenic potential of TCMTB in male and female CD-1 mice.

Classification of Carcinogenic Potential

The Health Effects Division Carcinogenicity Peer Review Committee (CPRC) met on June 28, 1995 to discuss and evaluate the weight-o f-the-evidence on 2-(Thiocyanomethylthio) benzothiazole (TCMTB) with particular refe rence to its carcinogeni c potential. Based on statistically significant increases in tumors in both sexes of the Sprague-Dawley rat: testicular interstitial cell adenomas in males and thyroid c-cell adenomas in females, the CPRC concluded that TCMTB should be classified as Group C - possible human carcinogen - and recommended that for the purpose of risk char acterization, the Reference Dose (RfD) approach should be used for quantitation of human cancer risk.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 50 of 68 

## Mutagenicity

The data base for mutagenicity is considered adequate and no additional studies are anticipated to be required at this time. TCMTB was negativ e for mutagenicity in the gene mutation assay with bacteria (MRID# 41386101), and did not caus e an increase in unscheduled DNA synthesis (UDS) in rat primary hepatocytes assay (MRID# 00165518). It was also negative for chromosomal aberrations in the in vivo micronucleus assay in mice (MRID# 00165520). In addition to the studies listed below, the agency is reviewing three genotoxi city studies received since the 2006 RED (MRIDs 46947216, 46947217, and 46947218).

Study Type: Mutagenicity Test on TCMTB in the Salmonella/Mammalian-Microsome Reverse Mutation (Ames Test) with Confirmatory Assay
In an Ames assay (MRID# 41386101) TCMTB was negative for inducing reverse gene mutations in Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98, or TA100 exposed in the presence or absence of S9 activation up to cytotoxic doses (  33.3 ) g/plate -S9;  66.7 ) g/plate +S9). The results were confirme d in an independently performed trial.

Study Type: Evaluation for Structural Chromosomal Aberration of TCMTB (EPA Reg. No.: 1448-29): Clastogenic Evaluation in th e In Vivo Mouse Micronucleus Assay

In a structural chromosomal aberrati on assay (MRID# 00165520), the high dose of TCMTB (500 mg/kg) exhibited mo rtality and signs of clinical toxicity. No evidence of an increase in micronucleated polychrom atic erythrocytes was noted at th e dose levels tested in this study (50, 167 and 500 mg/kg). There was evidence of some PCE depression at the high dose in the 48 and 72 hour animals.

Study Type: Evaluation of Other Genotoxic Effects of TCMTB (EPA Reg. No.: 1448-29). In the Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay

In an UDS assay (MRID# 00165518), TCMTB did not cause a significant increase in the unscheduled DNA synthesis (UDS) in rat primar y hepatocytes as measured in this study.



## Immunotoxicity

There is no immunotoxicity database for TCMTB. The agency anticip ates the need to require an immunotoxicity study for registration review.



## Neurotoxicity

There is no neurotoxicity database , acute or subchronic, for TCMT B. The agency anticipates the need to require an acute and 90-day neur otoxicity studies for registration review.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 51 of 68 

## Other Toxicological Effects

2-Mercaptobenzothiazole (2-MBT) is the main mammalian urinary metabolite of TCMTB, and has been suggested as a biological marker of e xposure to TCMTB (Manninen et al. 1996). In this study, three doses of TCMTB in olive oil were given to male rats by gavage for 3 weeks. Urine was collected daily and the metabolites were analyzed as thioethers by derivatization with pentafluorobenzylbromide by gas chromatography -mass spectrometry. The parent chemical was not detected in urine sample s, but two metabolites of TCMTB were identified.

2-Mercaptobenzothiazole (2-MBT) was the main metabolite, and its excretion varied according to the dose. The second metabolite was 2-(mer captomethylthio)benzothiazole. The amount of 2-MBT excreted in rat urine was 66 r 12% (SD), 51 r 20% and 44 r 9% for TCMTB doses of 15, 75, and 150 mg/kg, respectively. Two doses, 75 and 150 mg/kg , caused diuresis in rats during the 1 week of dosing. During the 3-week TCMTB treatment, rat liver microsomal CYP enzyme profile was not significantly changed. Urine samples for sawmill workers exposed to TCMTB were collected after their work shifts for exposure assessment. TCMTB could not be detected in the urine samples of exposed worker s. Most concentrations of 2-MBT were below the limit of detection, 0.12 P mol/l, the concentrations were 0.12-0.15 P mol/l only in few cases. The authors conclude that the determination of 2-MBT in urine, when a sample is taken immediately after a work shift, is a suitable indicator of workersS exposure to TCMTB.

In a rat metabolism study (MRID 40884801) 14C-TCMTB as administered to Sprague Dawley rats (5/sex/dose) by oral gavage at single doses of 3 and 30 mg/kg, and at a repeated oral dose of 3 mg/kg. Excretion of TCMTB derived radioactiv ity was monitored, as well as measurement of plasma levels and excretion of TCMTB derived ra dioactivity in bile. Metabolites of TCMTB in urine, plasma, and bile were characterized us ing thin layer chromatography. Absorption of TCMTB was rapid, with 80% excreted in urine by 24 hours post-dose at both the 3 and 30 mg/kg dose levels. In bile, cannulated rats, there was a marked reduction in 0-24 hour urinary excretion (25-35%).

Distribution data indicated that red blood cells and kidney were the only sites of significant retention of residual radi oactivity. However, these levels were low (0.02-2.41 P g equiv./g tissue). Measurement of elimination of radioactiv ity from blood showed that the half-life in red cells might be in excess of 7 days.

Excretion of TCMTB derived radi oactivity was mainly in urine, with between 80-85% of the total dose excreted in non-ca nnulated rats. Fecal excreti on comprised about 5% of an administered dose, and was not altered in cannulated rats, suggesting reabsorption of radioactivity from the gastrointestinal tract and excretion in urine. Pharmacokinetic data indicated that clearance was approximately equal at both the low and high dose, and the AUC was proportional to the dose, suggesting first orde r elimination at both the low and high dose.

Metabolite characterization us ing radio-TLC showed the presence of one and possibly 2 metabolites of TCMTB in urine and bile. However, definitive identification was not made, other than to suggest that at least one metabo lite could be a glucur onide conjugate.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 52 of 68 This metabolism study in the rat is classified as UNACCEPTABLE - GUIDELINE and does not satisfy the guideline requirement for a metabolism study [OPTTS 870.7485, OECD 417] in rats because there are incomplete data for the repeated low oral dose group, incomplete identification of metabolites and the purity of TCMTB was not reported. Though this study is considered unacceptable, the agency does not anticipate the need to require additional metabolism studies due to availability of acceptable chronic/carcinogenicity studies.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 53 of 68 

# Appendix B Environmental Fate

Environmental Fate and Transp ort Properties of TCMTB and Degradates

Hydrolysis

In a hydrolysis study conducted under abio tic and buffered conditions, 2-(thiocyano methylthio)benzothiazole (TCMTB), appeared hy drolytically stable at pH 5, degraded very slowly at pH 7 and only up to 10% after 35 days. It degraded at pH 9 (half-life = 2.1 days). The study was conducted between 25.2 to 27.5 R for up to 35 days (pH 5 and pH 7) or for 21 days at pH 9. The major degradate of 2-mercaptobenzot hiazole (MB) was present at a maximum of 10.2% of the applied radioactivity at 35 days post -treatment in the pH 7 buffer solution and at a maximum of 98.8% at 21 days post-treatment in the pH 9 buffer solution. In a second study on hydrolysis of TCMTB, degradati on of TCMTB was noted at pH 9 with a half -life of 1.8 days. The second study was also conducted under abio tic and buffered conditions (MRID Nos. 423861-01 and MRID No. 434376-01). The studies we re accepted as supplemental and no additional data is anticipate d to be required (161-1).

Aqueous Photolysis

Since the hydrolysis study showed that TCMT B was stable at pH 5 only, a photodegradation study was conducted in a pH 5 buffered aqueous so lution, which was irradi ated over an 8-hour period with artifi cial light at 25 R , TCMTB degraded with a half-life of 1.5 hours. The dark control solution showed that TCMTB was stable . Main degradation pr oducts were: MB (75.1%) of the applied radioactivity fo llowing 6 hours of irradiation. The second and a minor degradate of 2,2'-(dithiobis)benzothiazole (DBB) was at a maximum of 9.3% of the applied radioactivity following 7 hours of irradiation. (MRID No. 42 6309-01). The study fulfilled the fate data requirement and no additional data are anticipated to be required (161-2).

Octanol-Water Partition Coefficient/Bioaccumulation and Bioconcentration

The Kow of TCMTB is 1995. A Kow >1000 indi cates that a chemical may potentially bioconcentrate; however, the results of a bioconcen tration study in fish as shown below indicate that bioconcentration of TCMTB will be minimal.

A 63-day study (28-day bioconcentration and 35 -day depuration period) was conducted to evaluate the bioconcentration of TCMTB in bluegill sunf ish under flow-through aquarium conditions. Analysis of fillet, whole fish, a nd visceral portions were performed throughout the exposure period. Maximum bioconcentration factor s (BCFs), based on tota l radioactivity, were 302X for viscera, 64X for fillet, and 184X for wh ole fish tissues. The maximum concentrations of residues were 27 P g/kg (14 days) for the fillet tissue, 130 P g/kg (28 days) for the viscera tissue, and 79 P g/kg (28 days) for the whole fish tissue. During depuration, 48%, 58%, and 47% of the mean residues that accumulated by 14-28 days were eliminated by 1 day from the fillet,Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 54 of 68 viscera and whole fish tissues, respectively, a nd 75-77%, 84-87%, and 84-86% were eliminated by 21-35 days. During depuration, total residues in the water were below the limit of quantitation (0.00958 P g/L) from day 3 to 35.

The results indicate that TCMTB bioacummulates and bioconcentrates in fish tissues, it also depurates more than 75% by da y one after the twenty eight day study. The Agency concludes that since the depurated residue s were below the LOQ from day 3 to day 35 it is not of risk concern to the aquatic species.

However, in the second phase of this study, re sidues were characteri zed in the viscera and fillet tissues collected at 21 a nd 28 days of exposure. Total residues were 120 and 130 ppb in the viscera tissue, and 23.0 and 19.0 ppb in the fillet tissue at 21 and 28 days, respectively. The parent compound was present at 65.7 and 47.3 ppb in the viscera tissue, and at 7.3 and 11.8 ppb in the fillet tissue at 21 and 28 days, respectivel y. Three unidentified minor metabolites were each present in the fillet tissues at 2.3 ppb, a nd five unidentified minor metabolites were each present in the viscera tissues at 9.1 ppb levels. The results of th e two studies strongly indicate that though some residues were char acterized, overall the tendency of TCMTB in the fish system was to degrade, and that may be a reason of the study authors being unable to detect the parent as the residues were below the level of quantitati on (LOQ). The study is acce ptable and fulfils the fate data requirements (MRID 42418501) and no addi tional data is anticipated to be required.

Aerobic Aquatic Metabolism

In a study on an aerobic aquatic system, TCMTB degraded in flooded lake sand sediment, that was incubated at 22-26 ( C for up to 31 days. The calculated degradation half-life was 6.9 days; however, the apparent half-life occurred between 2 and 4 days pos t-treatment. In the aqueous phase, the major degradate of MB was pres ent at a maximum of 23.6% of the applied radioactivity at 31 days post-treatment. An unidentified major degrad ate was present at a maximum of 30.5% at 14 days post-treatment. In the sediment phase, the degradate MB was present at a maximum of 6.9% of the applied radioactivity at 24 days post-treatment. Nonextractable [ 14 C] residues, comprised of a minimum of 7 components, were a maximum of 28.3% at 24 days. The majority of the residues were observed in the water phase. While this study is scientifically valid, it does not meet gui delines for the fulfillment of data requirements (OPPTS 162-4) on aerobic aquatic metabolism b ecause the degradate that reached 30.5% was not identified. This study is acceptable/supple mental (MRID No. 425086-01). No additional data are anticipated to be required.

Anaerobic Aquatic Metabolism

A study of the anaerobic metabolis m of TCMTB in lake water and sediment was also conducted. Samples of lake water and sedi ment were incubated at 25 ± 1 ( C for up to 58 days. In this study, TCMTB degraded (calculated half-life = 2.7 da ys) under anaerobic aquatic conditions to two major degradates, MB and DBB. DBB was pres ent at a maximum of 67.7% of the applied radioactivity at 14 days post-tre atment; MB was at a maximum of 30.8% 58 days post-treatment. Other minor degradation products were also foun d. The majority of the residues were observed in the water phase. This study satisfies the an aerobic aquatic metabolism guideline requirements (OPPTS 162-3) (MRID No. 428154-01) and no additiona l data are anticipated to be required.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 55 of 68 Soil

Soil Leaching/Adsorption/Desorption Batch Equilibrium

The adsorption/desorption characteristics of TCMTB were studied on five representative agricultural soils: sand, sandy loam, silt loam, cl ay and clay loam. The study determined TCMTB to be very mobile in clay loam, sand, an d sandy loam soil, and mobile in clay and silt loam soil. Freundlich K ads values were 3.5 for the clay loam soil, 0.99 for the sand soil, 9.9 for the sandy loam soil, 22.1 for the clay soil, and 62.7 for the silt loam soil and corresponding K oc values were 282, 765, 2120, 2554, and 7896 mL/g. Freundlich K des values were 3.3 for the clay loam soil, 1.9 for the sand soil, 7.6 for the sandy loam soil, 13.0 for the clay soil, and 79.2 for the silt loam soil; corresponding K oc values were 262, 1480, 1627, 1504, and 9973 mL/g. This study satisfies the adsorption/desorption guidelin e requirements (OPPTS 163-1) (MRID No. 426314- 01) and no additional data is anticipated to be required.

Aerobic Soil Metabolism

The soil metabolism of TCMTB was studied under aerobic conditions using sandy loam soil, a representative agricultural soil. The soil was ma intained at 75% moisture content and incubated in darkness at 25 ± 1 ( C for up to 58 days. TCMTB degraded with a calculated half-life of 1.4 days. TCMTB degraded to four identified metabolites, MB, 2-benz othiazolol (BTOL), benzothiazol sulfonic acid (BTSA), DBB, and se ven other minor unidentified metabolites. The major degradate BTSA was present at a maximu m of 70.8% of the applie d radioactivity at 58 days post-treatment and the major degradate MB was present at a maximum of 30.3% at 1.5 days post-treatment. The minor degradates of DBB and BTOL were present at respective maximums of 6.7% (1 day) and 7.0% (21 days) of the applied radioactivity. This study is scientifically valid and is acceptable although it does not satisf y guidelines (OPPTS 162-1) for aerobic soil metabolism (MRID No. 435322-01). The agency how ever, does not anticipate the need to require additional studies.

Anaerobic Soil Metabolism

No study was submitted; however, the agency can bridge data from the aerobic soil metabolism for this case. No additional data are anticipated to be required.

Degradates of TCMTB

The key P/chem and fate characteristics of the de gradates are presented in the table below. These are estimated characteristics based on EPAS s EPI Suite Estimation Program ,version 4.3. (accessed on April 10, 2014).

Table B1: P/Chem and Some Fate Characteristics of DegradatesDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 56 of 68 NameCas# mp/bp/ ( o C) Vapor
pressure (mm Hg) Solubility in water (mg/L) Log K ow Ready biodeg. Half life in air (hours) STP Removal (%) K oc

L/Kg

2 (3H)- benzthiazolone :934-34-9 84 5.41 x10 -6 2354 2.35 NO 5.577 2.10 63.48

2 (3H)- benzthiazolethione: 149-30-4 62.56 4.21 x 10 -5 543.4 2.86 NO 3.15 2.89 125.9

2- benzthiazolesulfoni c acid :941-57-1 163.14 6.3 x10 -7 2.55 x10 +5 (-) 0.989 0 NO 78.43 1.85 2.38

-benzothiazole, 2,2 dithio: 120-78-5 213 2.55 x 10 -8 0.64 4.65 NO 24 minutes 64 1.1 x10 4

The estimated characteristics of the degradates of TCMTB show that the solubility of these degradates appear to vary from highly slightly to ve ry little soluble in wate r. All degradates have low vapor pressure and are not likel y to volatilize from surface water. Once in air their half lives in the air vary between 24 minutes to three hours to about three da ys, and are not possibly persistent in the atmosphere. The log K ow of these degradates are less than 3, except the dithio which has a log Kow of 4.6. Only the dithio degradate is likely to be highly bioaccumulative.. These degradates are not readily biodegradable and are persistent in water and waste waters. Their removal from sewage treatment plants (STP) is less than three percent except for the dithio which is removed 64% from STP treatment.

The estimated water to soil partition coefficient K oc less than 3 to 129 L/Kg indicating that these degradates are mobile to not mobile from soil surf aces. Again the dithio has a very high value of K oc of > 1 x10 4 L/Kg, which makes it immobile from the soil surfaces.

Environmental Fate Data Requireme nts for the Degradates of TCMTB.

At this time the agency anticipates the need to require the following studies for the two degradates, 2-Mercaptobenzth iazole (MB), and Benzothiazo l sulfonic acid (BTSA):

x Activated Sludge Respiration Inhibition (O ECD 209) or Modified Activated Sludge Respiration Inhibition (OCSPP 850.3300);

x Ready biodegradability test (835.3110) or one of three biodegradation in activated sludge simulation tests (835.3220; 835.3280; 835.3240)Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 57 of 68 

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Organisms

Birds, acute and dietary

One available acute-oral study categorizes technical-grade TC MTB as being slightly toxic to birds and another categorizes a major degradate (2-MBT) as bei ng practically nontoxic. The guideline (850.2100) is satisfied. Three dietary studies indicate that TCMTB is practically nontoxic and 2-MBT as slightly to practically no ntoxic when administered in the diet. The guideline (850.2100) is satisfied. No additional avian toxicity data are anticipated to be needed for the antimicrobial use patterns.

Avian Acute-oral and Dietary Toxicity

Test Species Test Material (% ai) Toxicity Toxicity Category EPA Study ID

Northern bobwhite ( Colinus virginianus ) TCMTB (80.4) LD50 = 600 mg ai/kg bw Slightly toxic 41780901 Acceptable

2-MBT (98.2) LD50 >2150 mg ai/kg bw Practically nontoxic 42267101 Acceptable

TCMTB (80) LC50 >4496 ppm Practically nontoxic 41595601 Acceptable

2-MBT (98.22) LC50 >3387 ppm Not determined - but no more than

slightly toxic 42428501 Acceptable

TCMTB (75) LC50 >10,000 ppm Practically nontoxic 00112617 Supplemental

Mallard ( Anas platyrhynchos ) TCMTB (80) LC50 >4496 ppm Practically nontoxic 41595602 Acceptable

TCMTB (80) LC50 >10,000 ppm Practically nontoxic 00078544 Acceptable

Nontarget Insects

No data are available. Toxicity data for beneficial insects (85 0.3020, acute contact) are anticipated to be needed to support the wood preservative use pattern.


### Toxicity to Aquatic Organisms

Freshwater Fish

The available acute toxicity studies categori ze technical-grade TCMTB as being very highly toxic to freshwater fish. One a dditional study indicates that the degradate 2-MBT is highly toxic.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 58 of 68 The guideline (850.1075) for acute toxi city testing is satisfied. Th e two available chronic studies indicate that TCMTB impacts re production, growth, and survival at low concentrations. The guideline (850.1400) for freshwater ch ronic testing is satisfied. No additional data are anticipated to be required.

Acute Toxicity to Freshwater Fish

Test Species Test Material (% ai) Toxicity Endpoint (μg ai/L) Toxicity Category EPA Study ID

Acute:

Rainbow Trout ( Oncorhynchus mykiss) TCMTB (80.4) 96-h LC50 = 20.9 Very highly toxic 41818101 Acceptable

TCMTB (90) 96-h LC50 = 55.2 Very highly toxic TN2437 Supplemental

2-MBT (98.2) 96-h LC50 = 730 Highly toxic 42232201 Acceptable

Bluegill ( Lepomis macrochirus ) TCMTB (80.4) 96-h LC50 = 8.7 Very highly toxic 41804201 Acceptable

TCMTB (90) 96-h LC50 = 32 Very highly toxic TN2432 Supplemental

Chronic:

Rainbow Trout TCMTB (83.78) NOAEC = 0.34 LOAEC = 0.56 Reproduction, Growth, Survival 42595901 Acceptable

Fathead Minnow ( Pimephales promelas ) TCMTB (81.8) NOAEC = 1.0 LOAEC = 2.6 Growth 48806701 Supplemental

Freshwater Invertebrates

The acute toxicity studies for the waterflea ca tegorize technical-grade TCMTB as being very highly toxic to freshwater inve rtebrates. An additional study with 2-MBT categorizes this degradate as being moderately toxic. The gui deline (850.1010) for acute toxicity testing is satisfied. The one available chronic study indi cates that TCMTB impacts reproduction, growth, and survival at low concentrations. The guide line (850.1300) for freshwater chronic testing is satisfied. No additional data ar e anticipated to be required.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 59 of 68 Freshwater Invertebrates

Test Species Test Material (% ai) Toxicity Endpoint (μg ai/L) Toxicity Category EPA Study ID

Acute:

Waterflea ( Daphnia
magna ) TCMTB (80.4) 48-hr EC50 = 22 Very highly toxic 41838201 Acceptable

TCMTB (90) 48-hr EC50 = 23 Very highly toxic TN2427 Supplemental

2-MBT (100) 48-hr EC50 = 2900 Moderately toxic 42226001 Acceptable

Chronic:

Waterflea TCMTB (83.78) NOAEC = 0.89 LOAEC = 1.8 Growth 42559101 Supplemental

Estuarine/Marine Fish and Invertebrates

The three available acute studies categorize technical-grade TCMT B as being very highly toxic to estuarine/marine organisms. The guideline s for acute testing with fish ((850.1075), a bivalve (850.1025 or 850.1055), and mysid (850.1035) are satisfie d. No chronic data are available. Chronic data are anticipated to be needed for assessing risks to estuarine/marine organisms, because chronic exposure is expected for many uses of TCMTB. The guidelines for estuarine/marine fish (850.1400, early life-st age) and mysid (850.1350) are not satisfied. Because TCMTB degrades rapidly in the environmen t, most chronic exposure is anticipated to be to the degradates. Therefore, the chronic te sting is anticipated to be needed for 2-MBT, a major degradate in the water column.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 60 of 68 Toxicity to Estuarine/mari ne Fish and Invertebrates

Test Species Test Material (% ai) Toxicity Endpoint (μg ai/L) Toxicity Category EPA Study ID

Acute:

Sheepshead minnow ( Cyprinodon variegatus ) TCMTB (80) 96-h LC50 = 60 Very highly toxic 40363601 Acceptable

Mysid ( Mysidopsis bahia ) TCMTB (80) 96-h LC50 = 20.3 Very highly toxic 40363602 Acceptable

Quahog clam ( Mercenaria mercenaria ) TCMTB (80) 48-hr EC50 = 13.9 Very highly toxic 40363603 Acceptable

Chronic:

Fish sp. 2-MBT Data gap NA --

Mysid 2-MBT Data gap NA --

Aquatic Plants

One study is available for a vascul ar species and four studies for non-vascular species. The data indicate that aquatic plants are highly sensitive to expos ure to TCMTB. The guidelines for testing with a vascular speci es (850.4400), three algal speci es (850.4500), and cyanobacteria (850.4550) are satisfied. No additional da ta are anticipated to be needed.

Toxicity to Aquatic Plants

Species Test material (% ai) Toxicity (μg ai/L) EPA Study ID

Duckweed ( Lemna sp.) TCMTB (83.5) EC50 = 430 NOAEC = 150 44200901 Acceptable
Green algae (Pseudokirchniriella subcapitata ) TCMTB (81.839) EC50 = 64 NOAEC = 29 4 8721502 Acceptable

Marine diatom ( Skeletonema costatum ) TCMTB (81.839) EC50 = 2.7 NOAEC = 1.5 4 8721501 Acceptable

Freshwater diatom ( Navicula pelliculosa ) TCMTB (81.839) EC50 = 40 NOAEC = 24 48754401 Acceptable
Cyanobacteria ( Anabaena flos-aqua ) TCMTB (81.839) EC50 = 156 NOAEC = 116 48853701 AcceptableDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 61 of 68 Benthic Organisms

Based on environmental fate properties (i.e., K d >50 L/kg for silt loam soil; K oc Ss >1000 for sandy loam, clay, and silt loam soils), and because the half-life of TCMTB in sediment is <10 days, subchronic sediment toxicity testing is anticipated as being needed (850.1735, 850.1740). Because TCMTB degrades rapidly, the test material should be 2-MBT.

Terrestrial Plants

The results of the studies demonstrated phytotoxic effects that included adventitious growth, color change, leaf curl, chlorosis, necrosis, stem curl, a nd mortality in the vegetative vigor test. Phytotoxic effects were also demonstrated in the seedling emergen ce test and included leaf curl, chlorosis, necrosis, and mortality. For vegetative vigor, the most sens itive monocot species, based on biomass, was corn with a NOAEC of 0.6 lb ai/A and an EC 25 of 0.79 lb ai/A, and the most sensitive dicot species was soybean, based on survival, with a NOAEC and EC 25 values of <0.25 and 0.37 lb ai/A, respectively. For seedling emergence, the most sensitive monocot species w as corn, based on biomass, with NOAEC and EC 25 values of 3.36 and 23.15 lb ai/A, respectively, Th e most sensitive dicot was cabbage, based on survival, with NOAEC and EC 25 values of 10.21 and 9.93 lb ai/A, respec tively. The reviewer cautioned that the results for the seedling emergence test should be inte rpreted with caution based on unreliable results. No additional data are anticipated to be needed.

Species Test material (% ai) Toxicity (μg ai/L) EPA Study ID

Terrestrial Vascular Plants: Seedling Emergence TCMTB (81.8) EC 25 = 3.36 lb ai/A NOAEC = 23.15 lb ai/A for corn EC 25 = 10.21 lb ai/A NOAEC = 9.93 lb ai/A for cabbage 48859301 Acceptable

Terrestrial Vascular Plants: Vegetative Vigor TCMTB (30.6) EC 25 = 0.79 lb ai/A NOAEC = 0.6 lb ai/A for corn EC 25 = <0.25 lb ai/A NOAEC = 0.37 lb ai/A for soybean 4 88859201 AcceptableDocket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 62 of 68 Ecotoxicity References:

41780901 Campbell, S.; Grimes, J.; Smith, G. (1991) TCMTB: An Acute Oral Toxicity Study with the Northern Bobwhite: Lab Project Number: 210-110. Unpublished study prepared by Wildlife Int., Ltd. 20 p.

00078554 WARF Institute, Incorporated (1974) Repor t: WARF Institute No . 4043620. (Unpublished study received Mar 26, 1975 under 4F1613; submitted by Buckman Laboratories, Inc., Memphis, Tenn.; CDL:095525-D)

00112617 Knott, W.; Woodard, G. (1968) Busan 72: Safety Evaluation on Bob- white Quail. (Unpublished study received Sep 18, 1969 unde r 0F0954; prepared by Woodard Research Corp., submitted by Buck- man Laboratori es, Inc., Memphis, TN; CDL:091624-J)

41595601 Long, R. et al. (1990) TCMTB: A Dietary LC50 Study with the Northern Bobwhite: Project Number: 210-108. Unpublished study prepared by Wildlife International Ltd. 16 p.
41595602 Long, R. et al. (1990) TCMTB: A Dietary LC50 Study with the Mallard : Project No.: 210- 109: Lab Project Number: 210-109. Unpublished study prepared by Wildlife International Ltd. 16 p.
00112616 Knott, W.; Woodard, G. (1968) Busan 72: Safety Evaluation on Blue- gill Sunfish and Rainbow Trout. (Unpublished study received Sep 18, 1969 under 0F0954; prepared by Woodard Research Corp., submitted by Buckman Laboratories, Inc., Memphis, TN; CDL: 091624-I)
41804201 Machado, M. (1991) TCMTB--Acute Toxicity to Bluegill Sunfish (Lepomis macrochirus) under Flow-through Conditions: Lab Project Number: 91-1-3621: 995.0390.6122.105. Unpublished study prepared by Springborn Labs, Inc. 54 p.
41818101 Machado, M. (1991) TCMTB: Acute Toxicity to Rainbow Trout (Oncorhynchus mykiss) Under Flow-Through Conditions: Lab Proj ect Number: 91-1-3650: 90-TCMTB-02: 995.0390.6122.108. Unpublished study prepared by Springborn Laboratories, Inc. 55 p.
41838201 McNamara, P. (1991) TCMTB Acute Toxi city to Daphnids (Daphnia magna) Under Flowthrough Conditions: Final Report: Lab Project No.: 91-1-3617: 995.1190.6122.115. Unpublished study prepared by Springborn Laboratories, Inc. 56 p.
40363601 Surprenant, D. (1987) Acute Toxicity of TCMTB to Sheepshead Minnow (Cyprinodon variegatus): Bionomics Report #BW-86-12-2226; Bionomics Study #995.0686.6103.500. Unpublished study prepared by Springborn Bionomics, Inc. 18 p.
40363602 Surprenant, D. (1987) Acute Toxicity of TCMTB to Mysid Shrimp (Mysidopsis bahia): Bionomics Report #BW-87-1-2286; Bionomics Study #995.0686.6103.510. Unpublished study prepared by Springborn Bionomics, Inc. 16 p.
40363603 Surprenant, D. (1986) Acute Toxicity of TCMTB to Embryos-Larvae of the Quahog Clam (Mercenaria mercenaria): Bionomics Report # BW-86-12-2219; Bionomics Study #995.0686.6103.514. Unpublished study prepared by Springborn Bionomics, Inc. 18 p.
42559101 Blasberg, J.; Hicks, S.; Stuerman, L. (1992) Chronic Toxicity of TCMTB to Daphnia magna under Flow-through Test Conditions: A S upplement: Lab Project Number: 40089. Unpublished study prepared by ABC Laboratories, Inc. 56 p.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 63 of 68 42592901 Rhodes, J.; Stuerman, L. (1992) Early Life-s tage Toxicity of TCMTB to the Rainbow Trout under Flow-through Conditions: Final Report: Lab Project Number: 40088. Unpublished study prepared by ABC Labs, Inc. 470 p.
44200901 Thompson, S.; Swigert, J. (1996) TCMTB: A 14-Day Static-Renewal Toxicity Test with Duckweed (Lemna minor): Final Report: Lab Project Number: 210A-101. Unpublished study prepared by Wildlife International Ltd. 58 p. Relates to L0000129.
48806701 Minderhout, T.; Chafey, K.; Gallagher, S.; et al. (2012) 2-(Thiocynaomethylthio) Benzothiazole (TCMTB): An Early Life-Stage Toxicity Test with the Fathead Minnow (Pimephales promelas): Final Report. Pr oject Number: 210A/114. Unpublished study prepared by Wildlife International, Ltd. 100p.
48859301 Sindermann, A.; Porch, J.; Krueger, H. et al. (2012) 2-(Thiocyanomethylthio) Benzothiazole (TCMTB): A Toxicity Test to Determine th e Effects of the Test Substance on Seedling Emergence of Ten Species of Plants: Final Report. Project Number: 210/123. Unpublished study prepared by Wildlife International, Ltd. 107p.
48859201 Sindermann, A.; Porch, J.; Krueger, H. et al. (2012) 2-(Thiocyanomethylthio) Benzothiazole (TCMTB): A Toxicity Test to Determine the Effects of the Ten Substance on Vegetative Vigor of Ten Species of Plants: Final Report. Project Number: 210/124A. Unpublished study prepared by Wildlife International, Ltd. 181p.
48721501 Jacobs, A.; Porch, J.; Kendall, T.; et al . (2011) 2-(Thiocyanomethylthio) Benzothiazole (TCMTB): A 96-Hour Toxicity Test with the Marine Diatom (Skeletonema costatum): Final Report. Project Number: 210A/113. Unpublished study prepared by Wildlife International, Ltd. 54p.
48721502 Jacobs, A.; Porch, J.; Kendall, T.; et al . (2011) 2-(Thiocyanomethylthio) Benzothiazole (TCMTB): A 96-Hour Toxicity Test with the Freshwater Alga (Pseudokirchneriella subcapitata): Final Report. Project Number: 210A/112. Unpublished study prepared by Wildlife International, Ltd. 54p.
48754401 Jacobs, A.; Porch, J.; Kendall, T.; et al . (2012) 2-(Thiocyanomethylthio) Benzothiazole (TCMTB): A 96-Hour Toxicity Test with the Freshwater Diatom (Navicula pelliculosa): Final Report. Project Number: 210A/111A. Unpublished study prepared by Wildlife International, Ltd. 51p.
48853701 Jacobs, A.; Porch, J.; Kendall, T. et al . (2012) 2-(Thiocyanomethylthio) Benzothiazole (TCMTB): A 96-Hour Toxicity Test with the Freshwater Alga ( Anabaena flos-aquae ): Final Report. Project Number: 210A/110A. Unpublished study prepared by Wildlife International, Ltd. 52p.
TN 2427 USEPA. 1979. Biological Report of Analysis : 2-(thiocyanomethylthio) benzothioazole (90% active). Sample No. MB 618, Static Jar Test #2427, Terrestrial & Aquatic Biology Lab.
TN 2432 USEPA. 1979. Biological Report of Analysis: TCMTB 2-(thiocyanomethylthio) benzothioazole (90+). Sample No. MB 618, Static Jar Test #2432, Terrestrial & Aquatic Biology Lab.
TN 2437 USEPA. 1979. Biological Report of Anal ysis: 2-(thiocyanomethylthio) benzothioazole. Sample No. MB 618, Static Jar Test #2437, Terrestrial & Aquatic Biology Lab.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

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# Appendix D Screening Level Down-theDrain Analysis

The Down-the-Drain (DtD) module of E-FAST (E xposure and Fate Assessment Screening Tool), [version 2] was used to screen for the potential for aquatic organisms downstream of domestic wastewater treatment plants to be exposed to 2-(thiocyanomet hylthio) benzothiazole (TCMTB) and its degradates. The Down-the-Drain modul e uses daily per capita release of household wastewaters, stream dilution factors, and wast ewater treatment plant removal efficiency to provide both high-end and median (average) tim e-averaged surface wate r concentrations of chemicals discharged by domestic wastewater treatment plants. The high-end scenario uses surface water concentrations downs tream of domestic wastewater treatment plants based on the 10 th percentile stream dilution factor (SDF); the average scenario uses surface water concentrations based on the 50 th percentile SDF. SDF is defined as the ratio of the stream flow downstream of a wastewater treatm ent plant to the wastewater trea tment plant flow. Inputs used to run the DtD module included concentrations of concern (C OCs) for aquatic organisms, percent removal during wastewater treatment, and hypothetical wastewater treatment plant influent volumes. The results of the DtD module ar e expressed as number of days of exceedance of COCs for aquatic organisms. COCs are grouped into 3 categories: acute, endangered/listed, and chronic. Acute COCs for freshwater fish and invertebrates were derived by dividing LC 50 values for freshwater organisms by 2. Endange red/listed COCs for freshwater fish and invertebrates were derived by dividing LC 50 values by 20. EC 50 values for plants were used to establish acute COCs for plants. NOAEC valu es for plants were used to establish endangered/listed COCs for plants . Chronic COCs for freshwater fish and invertebrates are based on NOAEC values. For acute and endang ered listed COCs, there may be potential concern for freshwater organisms if the COC is exceeded for 1 day or more. For chronic COCs, there may be potential concern for freshwater organisms if the COC is exceeded 20 days or

more.

The Down-the-Drain module was first run using a high-end scenario, assuming a percentage of the production volume and 0% removal sorption or degradation to determ ine whether the model predicted exceedances of concentrations of concer n. Then an average scenario was used to run the DtD model.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

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# Appendix E Product Chemistry

TCMTB product chemistry information is su mmarized in Table E1 (source: MRIDs 41612003, 41612001, 41612002, 41612003, 42059701, 42059702, 42324501, and 42407401).

Table E1 – Product Chemistry of TCMTB

Guideline No. Physical and Chemical Properties TCMTB
830.1550 Product identity and composition Refer to Table 3. 830.1600 Description of materials used to produce the product Confidential Business Information (CBI)

830.1620 Description of production process CBI 830.1650 Description of Formulation Process CBI 830.1670 Discussion of Formation of Impurities CBI 830.1700 Preliminary analysis CBI 830.1750 Certified limits CBI 830.1800 Enforcement an alytical method HPLC 830.1900 Submittal of samples CBI 830.6302 Color Vivid orange/strong orange
830.6303 Physical State Semi-transparent orange liquid. Viscous liquid 830.6304 Odor Strong sour and pungent odor (like mineral oil)

830.6313 Stability to normal and elevated temperature, metals/metal ions Stable.
830.6314 Oxidation/Reduction Not required for products which do not contain oxidizing or reducing agents. 830.6315 Flammability Not flammable. Do not contain combustible liquids. 830.6316 Explodability Not explosive 830.6320 Corrosion Characteristic Not reported 830.7000 pH 5.99 (1:100 dilution in water)
830.7050 UV/Visible Absorption TCMTB absorbs UV light and undergoes direct photolysis 830.7100 Viscosity 352.4cSt 830.7200 Melting point Not applicable for liquids 830.7220 Boiling point Decomposes before boiling 830.7300 Density 1.376 g/m 3 830.7370 Dissociation Constant Not applicable for non-aqueous products
830.7550 Partition coefficient ( n -octanol/water) 3.23 ± 3% at 20 ஈ C 3.22 at 25 ஈ C 830.7840 Solubility in water 45 mg/L ± 15% in water at 25 ஈ C 830.7860 Solubility in organic solvents Soluble in most organic solvents 830.7950 Vapor pressure PAI: 2.34 x 10 -6 mm Hg; 4.08 x 10 -6 mm Hg (25 ஈ C)Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

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# Appendix F Comments Received Concerning the Preliminary Work Plan

On September 24, 2014 EPA opened a 60-day public comment period on the preliminary work plan (PWP) for the registration review of TC MTB. The comment period ended on November 24, 2014. The single comment received did not result in a modification to the anticipated data needs detailed in the TCMTB PWP.

The agency received a comment submission from the Center for Biological Diversity (Center) during the public comment period on the initial docket. The Cente rSs comment sought to confirm the agencySs coordinati on with the U.S. Fish and Wildlife Service and the National Marine Fisheries under Section 7 of the Endangered Species Act (ESA) to ensure that TCMTB does not jeopardize the continued existence of any listed species or result in adverse modification or destruction of critical habitat.Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 67 of 68 Comments Received on the Registration Review Preliminary Work Plan for TCMTB

Submitter: The Center for Biol ogical Diversity (Center)

1. Comment: The CenterSs comment focuses on the EPASs duty to consult with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the Services) on the registration review of TCMTB in accordance wi th the ESA. The Center mentions various aspects of the risk assessment process, includ ing use of the best ava ilable data to develop endangered species risk assessments, sources of data available to conduct an effects determination, and evaluation of effects on e ndangered and threatened species and their designated critical habitat. The Center also expressed concern regard ing the rigor of the agencySs preliminary determinations regard ing the effects of TCMTB on endangered and threatened (listed) species and their de signated critical habitat for the TCMTB registration review.

EPA Response: EPA has reviewed the comments fr om the Center on the registration review docket opening for TCMTB and plans to address many of the concerns raised by the Center as part of the implementation plan fo r assessing the risks of pesticides to listed species based on the recommendations of th e April 2013 National Academy of Sciences (NAS) report (also cited by the Center). EPA will address concerns specific to TCMTB in connection with the development of its final registration review decision for this pesticide.

In November 2013, EPA, along with the Serv ices and USDA, released a summary of their joint interim approaches for assessing ri sks to endangered and threatened (listed) species from pesticides. The interim approach es were developed jointly by the agencies in response to the NAS recommendations and reflect a common approach to risk assessment shared by the agencies as a way of addressing scientific differences between the EPA and the Services. The NAS report [1] outlines recommendations on specific scientific and technical issues related to th e development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA.

The joint interim approaches were released prior to a stakeholder workshop held on November 15, 2013. In addition, the EPA presen ted the joint interim approaches at the December 2013 Pesticide Program Dialogue Co mmittee (PPDC) and State-FIFRA Issues Research and Evaluation Group (SFIREG) meetings. The agenci es also held stakeholder workshops in April and October 2014, allowi ng additional opportunitie s for stakeholders to comment on the interim approaches. Additional workshops are planned to enhance stakeholder involvement. As part of a phased, iterative process for developing the interim approaches, the agencies will al so consider public co mments on the interim approaches in connection with the deve lopment of upcoming registration review decisions. The details of the joint interim a pproaches are contained in the white paper, Interim Approaches for National-Level Pes ticide Endangered Species Act Assessments

[1] http://www.nap.edu/catalog.php?record_id=18344Docket Number EPA-HQ-OPP-2014-0405 www.regulations.gov

Page 68 of 68 Based on the Recommendations of the National Academy of Sciences April 2013 Report [2] , dated November 1, 2013.

Given that the agencies are continuing to de velop and work toward implementation of the interim approaches to assess the potential risk s of pesticides to listed species and their designated critical habitat, this FWP for TCMTB does not describe the specific ESA analysis, including effects determinations for sp ecific listed species or designated critical habitat, to be conducted during registrati on review. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk assessments for endangered and threatened (lis ted) species and their designated critical habitats, these methods will be applied to subsequent analyses for TCMTB as part of completing this registration review.

[2] http://www.epa.gov/espp/2013/nas.html