Page 2 of 65

2-(Thiocyanomethylthio)-benzothiazole (TCMTB) Registration Review Team 

Antimicrobials Division 

Human Health & Environmental Effects 

Timothy Dole 

LT Jonathan Leshin 

William Erickson 

Srinivas Gowda 

Siroos Mostaghimi 

Najm Shamim 

Risk Management 

Sandra O’Neill 

Karen Leavy 

James Parker 

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-evaluation Division 

Steven Snyderman 

Avivah Jakob 

Office of General Counsel 

Philip Ross 
Docket Number EPA-HQ-OPP-2014-0405 

www.regulations.gov 

Page 3 of 65

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-m3

/mole atmospheric pressure-cubic meter per mole 

BCF bioconcentration factor 

BTOL 2-benzothiazolol 

BTSA benzothiazol sulfonic acid 

°C degrees Celsius 

CaSO4 calcium sulfate 

CaSO3 calcium sulfite 

CAS Chemical Abstracts Service 

CFR Code of Federal Regulations 

CHO Chinese hamster ovary 

CMA Chemical Manufacturers Association 

CO2 carbon dioxide 

COC concentration-of-concern 

cPAD chronic population adjusted dose 

DBB 2,2’-(dithiosbis) benzothiazole 

DCI data call-in 

EC50 median (or 50 percent) effect concentration

EC05 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, Drug, 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 

LC50 median (or 50 percent) lethal concentration 

LD50 median (or 50 percent) lethal dose 

LOAEC lowest-observed-adverse-effect-concentration 

LOEC lowest-observed-effect-concentration 

LOAEL lowest-observed-adverse-effect-level 

Log Kow logarithm of the octanol-water partition coefficient

MB 2-mercaptobenzthiazole 

μg microgram 
Page 4 of 65

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 Handler’s 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 plants 

 
Page 5 of 65

Table of Contents 

1 Introduction ............................................................................................................................. 7

1.1 Statutory and Regulatory Authority ................................................................................. 7

1.2 Case Overview ................................................................................................................. 9

1.3 Chemical Identification and Properties ............................................................................ 9

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

1.4.1 Registrations ........................................................................................................... 10

1.4.2 Summary of Registered Uses .................................................................................. 11

1.4.3 Usage Information .................................................................................................. 13

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

1.5.1 Tolerance Information ............................................................................................ 13

1.6 Incidents ......................................................................................................................... 14

1.6.1 Human Health ......................................................................................................... 14

1.6.2 Ecological ............................................................................................................... 14

2 Anticipated Data Needs ........................................................................................................ 15

3 Human Health Risk Assessment ........................................................................................... 19

3.1 Toxicological Endpoints ................................................................................................ 19

3.2 Dietary Exposure ............................................................................................................ 20

3.2.1 Residue Chemistry (Agricultural Uses Only) ......................................................... 21

3.2.2 Antimicrobial Uses ................................................................................................. 22

3.2.3 Agricultural Uses, Food and Drinking Water ......................................................... 22

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

3.3.1 Occupational Handler Exposure ............................................................................. 23

3.3.2 Residential Handler Exposures ............................................................................... 25

3.3.3 Residential Post-Application Exposures ................................................................. 25

3.4 Aggregate and Cumulative Exposure ............................................................................. 26

3.4.1 Aggregate Exposures .............................................................................................. 26

3.4.2 Cumulative Exposures ............................................................................................ 26

4 Environmental Risk Assessment........................................................................................... 26

4.1 Environmental Fate Assessment ......................................................................................... 27

4.1.1 Leaching From Treated Wood ................................................................................ 27

4.1.2 Water Quality .......................................................................................................... 28

4.2 Environmental Exposure Pathways ................................................................................ 28

4.3 Ecological Effects Assessment ....................................................................................... 29

4.3.1 Ecotoxicology Endpoints ........................................................................................ 29

4.4 Exposure Analysis Plan .................................................................................................. 30

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates ............................................ 30

4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 31

4.5 Effects Analysis Plan ..................................................................................................... 32

5 Endocrine Disruptor Screening Program (EDSP) ................................................................. 33

6 Optional Label Changes ........................................................................................................ 34

7 Guidance for Commenters .................................................................................................... 34

7.1 Preliminary Work Plan ................................................................................................... 34

7.1.1 Trade Irritants .......................................................................................................... 34

7.1.2 Water Quality .......................................................................................................... 34

7.1.3 Environmental Justice ............................................................................................. 34
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7.1.4 Structure Activity Relationships ............................................................................. 35

7.1.5 Additional Information ........................................................................................... 36

8 Next Steps ............................................................................................................................. 36

9 References ............................................................................................................................. 37

Appendix A Toxicology Profile ............................................................................................... 41

Appendix B Environmental Fate ............................................................................................. 53

Appendix C Ecotoxicology Profile .......................................................................................... 57

Appendix D Screening Level Down-the-Drain Analysis ........................................................ 64

Appendix E Product Chemistry ............................................................................................... 65

List of Tables 

Table 1 –Anticipated Risk Assessments and Data Needs for Registration Review: TCMTB ....... 8

Table 2 – Anticipated Registration Review Schedule .................................................................... 8

Table 3 – Chemical Identification of (Thiocyanomethylthio) benzothiazole (TCMTB) ............... 9

Table 4 – Physical-Chemical and Environmental Fate Properties for TCMTB ........................... 10

Table 5 – TCMTB Registered Antimicrobial Uses ...................................................................... 11

Table 6 – TCMTB Registered Agricultural Uses ......................................................................... 12

Table 7 – Studies Anticipated as Needed for the Registration Review of TCMTB ..................... 16

Table 8 – Data Needs Already Required by the May 19, 2010 Data Call-In for the TCMTB 

RED*............................................................................................................................................. 18

Table 9 – Existing Toxicological Endpoints ................................................................................. 19

Table 10 – Occupational Handler Scenarios to be Assessed during Registration Review ........... 23

Table 11 – Residential Handler Exposure Scenarios for TCMTB ............................................... 25

Table 12 – Residential Post-Application Exposure Scenarios for TCMTB ................................. 26

Table 13 – Identification of Major Degradates of TCMTB .......................................................... 27

Table 14 - Ecological Effects Endpoints for the Ecological Risk Assessment. ............................ 29

Table 15 - Summary of Screening Level Down-the-Drain Analysis for Aquatic Organisms ...... 31

 
Page 7 of 65

1 Introduction 

This document is the United States Environmental Protection Agency’s (USEPA, EPA or “the 

agency”) Preliminary Work Plan (PWP) for 2-(Thiocyanomethylthio)-benzothiazole, herein 

referred to as TCMTB. The PWP document explains what EPA's Office of Pesticide Programs 

(OPP) knows about TCMTB, highlighting anticipated data and assessment needs, identifying the 

types of information that would be especially useful to the agency in conducting the review, and 

providing an anticipated timeline for completing TCMTB’s review. 

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The agency intends, by sharing this information in the 

docket, to inform the public of what it knows about 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. The agency encourages all interested stakeholders to review the PWP and to provide 

comments and additional information that will help the agency’s decision-making process for 

this chemical. 

1.1 Statutory and Regulatory Authority 

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States generally must be registered by the USEPA 

based on scientific data showing that they will not cause unreasonable risks to human health or 

the environment when used as directed on product labeling. The registration review program is 

intended to make sure that, as the ability to assess risk evolves and as policies and practices 

change, all registered pesticides continue to meet the statutory standard of no unreasonable 

adverse effects to human health or the environment. Changes in science, public policy, and 

pesticide use practices will occur over time. Through the registration review program, the agency 

periodically reevaluates pesticides to make sure that as change occurs, products in the 

marketplace can be used safely. Information on this program is provided at 

http://www.epa.gov/oppsrrd1/registration_review/. 

The agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The agency 

will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. After 

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

comment period, the agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the TCMTB case. 

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

in docket EPA-HQ-OPP-2014-0405. Table 1 and Table 2 below summarize the issues relevant to 

this registration review case and the anticipated registration review schedule. 
Page 8 of 65

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 Method3

Dietary (food) No 

(see 3.2.1) 8/1/2006 None None 

Dietary (drinking water) Yes1 8/1/2006 New None 

Occupational Handler Yes 4/19/2006 Updated 

Indoor Exposure Data 

Acute Neurotoxicity2

Immunotoxicity2

90-Day Neurotoxicity2

90-Day Inhalation2

Residential Handler Yes 4/19/2006 Updated 

Indoor Exposure Data 

Acute Neurotoxicity2

Immunotoxicity2

90-Day Neurotoxicity2

90-Day Inhalation2

Residential Post 

Application - Incidental 

Oral and Dermal 

Yes 4/19/2006 Updated 

Acute Neurotoxicity2

Immunotoxicity2

90-Day Neurotoxicity2

Aggregate Yes 8/1/2006 Updated 

Acute Neurotoxicity2

Immunotoxicity2

90-Day Neurotoxicity2

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 risk assessments and data needs for Registration 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 required only for agricultural use. 

Table 2 – Anticipated Registration Review Schedule 

Anticipated Activity Target Date* Completion Date

Phase 1: Opening the Docket 

Open Docket and 60-Day Comment Period for Preliminary Work Plan 2014-09 09-24-14 

Close Public Comment Period 2014-11 

Phase 2: Case Development 

Issue Final Work Plan 2015-03 
Page 9 of 65

Issue Data Call-In (DCI) 2016-03 

Receive Data to be Considered in Risk Assessment 2018-03 

Open 30-Day Public Comment Period for 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).

1.2 Case Overview 

The docket for TCMTB (case 2625) has been established at http://www.regulations.gov in 

docket number EPA-HQ-OPP-2014-0405. 

. 

1.3 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 (Thiocyanomethylthio) benzothiazole (TCMTB) 

Chemical Name TCMTB 

Chemical Classification Mercaptobenzothiazole; Thiazole; Thiocyanate 

PC Code 035603 

CAS Number 21564-17-0 

Molecular Formula C9H6N2S3

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 chemistry (Source: MRIDs 41612003, 41612001, 41612002, 
Page 10 of 65

41612003, 42059701, 42059702, 42324501, 42407401) and environmental fate information are 

discussed in Appendix E and Appendix B , respectively.

Table 4 – Physical-Chemical and Environmental Fate Properties for TCMTB 

Parameter TCMTB 

PHYSICAL/CHEMICAL CHARACTERISTICS 

Boiling point (oC) 191 oC, decomposes before boiling 

Density 1.376 g/cm3 

Octanol-water partition coefficient (Kow) 3.22 at 25oC; highly bioaccumulative, but depurates 

within 28 days 

Solubility in water (mg/L) 45 mg/L ± 15% in water at 25oC 

Vapor pressure (mmHg) PAI: 2.34 x 10-6 mm Hg 

ENVIRONMENTAL FATE PROPERTIES 

Mobility

Organic Carbon Partitioning Coefficient (Koc) 283-7896 in 5 soils 

Persistence in Water (half-life)

Hydrolysis at 25 oC: pH 5, 7 &9 (days) 

Stable at pH 5; it degrades at pHs 7, and 9 with a 

half- life of 2.1 days (MRID No. 423861-01 and 

MRID No. 434376-01). (see degradates in Appendix 

B) 

Aqueous photolysis at 25 oC (days) Half life at pH 5 is 1.5 hours. (MRID No. 426309-

01); (see degradates in Appendix B) 

Aerobic aquatic metabolism (days) half lives range from 2 to 7 days. (MRID No. 425086-

01); see degradates in section Appendix B 

Anaerobic aquatic metabolism half-life (days) half- life of 2.7 days (MRID No. 428154-01) 

(See degradates in Appendix B) 

Persistence in Soil (half-life)

Soil photolysis (days) Not required (See Appendix B) 

Aerobic soil metabolism at 25 oC (days) half -life of 1.4 days; (MRID No. 435322-01). 

See degradates in Appendix B 

Anaerobic soil metabolism (days) Not required (See Appendix B) 

Persistence in WWTP (% removed)

Ready biodegradation No data submitted, anticipated data requirement 

Adsorption/ Desorption or Batch Equilibrium 

study Kd

Range from 0.99 in sand to 62.7 in silt loam 

Kdes: 1.9-79.2 (MRID#426314-01) oC = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury; 

1.4 Use/Usage Description 

1.4.1 Registrations 

There are 27 EPA-registered products that contain TCMTB as an active ingredient (a.i.). One 

end-use product has agricultural 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 packaging, all of the products containing TCMTB are 

formulated as liquids. It should also be noted that one product listed in EPA’s database as a 
Page 11 of 65

wettable powder (EPA Reg. No. 1448-376) is actually a liquid. The label lists a product weight 

of 1.0 kg per liter and includes use directions that are given in fluid ounces. 

During registration review, the agency will work with registrants to clarify whether labels and 

use patterns are or are not intended for food or non-food contact. 

1.4.2 Summary of Registered Uses 

Table 5 and Table 6 present a listing of the registered uses of TCMTB. EPA Reg. No. 264-965 

was cancelled on 1-15-141. 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 the same as the uses that were assessed in the 

2006 RED. The paint uses have been removed from all labels; however, the textile use is still 

included on two end use product labels (#1448-440 and 81910-3) and four formulation 

intermediate labels (1448-401, 1448-403, 1448-405, 1448-407) and must be removed. The 

agency is reviewing TCMTB product labels to make sure they reflect labeling changes specified 

in the 2006 RED. With the exception of the textile use, all of the uses listed in Table 5 will be 

assessed in this registration review. TCMTB can be applied by the following application 

methods: open pour, brush, spray, dip treatment and pressure treatment. 

1.4.2.1 Antimicrobial Uses 

TCMTB products are used in commercial/institutional 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 products, surface coatings, adhesives, caulks, and 

sealants), and also as a wood preservative and 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. 

1.4.2.2 Agricultural Uses 

TCMTB is registered for use as an agricultural pesticide for seed treatment (on rice, safflower, 

and cotton). NUSAN® 30 E.C. (EPA Reg. No. 2935-389) contains 2.635 pounds of TCMTB per 

gallon. NUSAN ® 30 E.C. is recommended for the control 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 water. The recommended 

maximum rates may be dispersed in as much as 16 fl. oz. of water and applied to 100 lbs. of 

seed. 

Table 5 – TCMTB Registered Antimicrobial Uses 

Use Application 

Method 

Application Rate 

(ppm a.i.) 

 

1

 February 26, 2014 – Published the Product Cancellation Order for Certain Pesticide Registrations in the Federal 

Register (79 FR 10800) (FRL-9905-34) 
Page 12 of 65

Industrial Process and Water Systems 

Cooling Tower Wood – Circulate in Place Treatment 

Cooling Tower Wood – Surface Treatment 

Cooling Water Systems - Initial Treatment 

Cooling Water Systems – 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 – 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 Machines 

Metal 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 

Textiles1

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 (Lumber and Timbers) Dip, Spray, Brush, 

Pressure 

1,200 to 50,000 

1

The textile use was deemed ineligible in the RED but it remains on two product labels (1448-440 and 81910-3) and 

four formulation intermediate labels (1448-401, 1448-403, 1448-405, 1448-407). 

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 
Page 13 of 65

Rice 1.25 129 0.0332 

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

1.4.3 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. 

1.5 Regulatory History 

The first pesticide product containing TCMTB was registered by the EPA on January 21, 1980. 

The agency assessed TCMTB as a dual-use chemical and completed a RED in 2006. The agency 

issued a post-RED generic data call-in (GDCI-035603-29761) on May 19, 20102. 

1.5.1 Tolerance Information 

There are 25 tolerances listed in 40 CFR 180.288 for TCMTB. The agency anticipates reviewing 

all active tolerances/exemptions during the registration review process. 

1.5.1.1 Antimicrobial Uses 

For the active ingredient TCMTB, EPA has no tolerances or exemptions from tolerances 

established for use antimicrobial 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 for use as an antibacterial preservative in 

paper and paperboard components (21 CFR 176.300). 

1.5.1.2 Agricultural Uses 

The current tolerance expression does not comply with OPP’s Health Effects Division’s (HED) 

policy on tolerance expression. In addition, HED reviewed some recently submitted data for 

TCMTB and it appears that a tolerance for cotton gin byproduct may need to be established. 

Established tolerances on cotton, undelinted seed, rice grain, and safflower grain should be 

maintained to support the seed treatment uses for TCMTB on cotton, rice and safflower. The 

registrant has voluntarily cancelled uses of TCMTB as a fungicide on barley, sugar beets, corn, 

oats, sorghum, and wheat3

. The agency is working with registrants to revoke the tolerances for 

the cancelled commodities. There are no Codex/Canadian Maximum Residue Limits (MRL) 

established on TCMTB. 

 

2

 For the studies required through the post-RED DCI, see Table 7. 

3

 February 26, 2014 – Published the Product Cancellation Order for Certain Pesticide Registrations in the Federal 

Register (79 FR 10800) (FRL-9905-34) 
Page 14 of 65

1.6 Incidents 

1.6.1 Human Health 

Individual Incident Reports 

Incidents that are rated as moderate (HC) or higher are reported in individual reports which 

include information regarding the causes of the incident and symptoms experienced. In the case 

of TCMTB, six human health individual incident reports are listed 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 incidents are classified as human moderate (HC). Summaries of 

these incidents are included below. These summaries are provided for information purposes only 

to aid in risk management and are not meant to be a formal interpretation of cause and effect. 

 A chemical service company worker experienced 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 began to occur when the worker was in other 

areas of the mill where only the diluted product was used. 

 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 

bung hole cap. 

 A sapstain treatment worker alleged that TCMTB products have caused his knees to 

swell. He maintained dip chemicals for 10-11 yrs. 

 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. 

 A reporter working as a temporary worker for one day in a tannery received a facial 

chemical burn when treating “wet blues” (a stage of leather production) with a TCMTB 

product. 

 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) are reported in aggregate 

reports which are listings of the incidents for a manufacturer or distributer over a certain time 

period (often quarterly). Typically these reports only contain basic information such as the date, 

location and product involved and more detailed information such the cause of the incident or 

symptoms experienced are not included. In the case of TCTMB, there are 12 aggregate incidents 

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. 

1.6.2 Ecological 

No ecological incidents have been reported in the agency’s Incident Data System as of April 22, 

2014. A review of the Ecological Incident Information System (EIIS, version 2.1) and the Avian 

Monitoring Information System (AIMS) was completed on August 8, 2014, and no ecological 
Page 15 of 65

incidents were identified. Incident databases will be reviewed again at the time of the risk 

assessment. 

2 Anticipated Data Needs 

Several studies were required from the assessment 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 TCMTB. 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 16 of 65

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

830.1800 Enforcement analytical method TGAI 12 Residue Chemistry Seed treatment 835.3110 1,2 835.3220835.3240835.3280 

Ready biodegradability or one of three biodegradation in activated sludge simulation tests 

Degradates8 24 

Fate and persistence in WWTPs Down the drain assessment 

Material Preservatives Metal Working Fluids Industrial Processes and Water Systems Wood Preservatives 

850.13005 Mysid chronic toxicity 

Degradates7

12 

Aquatic organisms 

Materials Preservatives, Wood Preservatives, Industrial Processes and Water Systems 

850.14005 Fish early-life stage, estuarine/marine species 12 850.17354

Whole sediment subchronictoxicity, freshwater invertebrates (2 spp.) 

12 

850.17404

Whole sediment subchronictoxicity, estuarine/marine invertebrate 

12 

850.2100 Avian acute oral (passerine) TGAI 12 Terrestrial organisms Seed treatment 850.3020 Honey bee acute contact toxicity TGAI 12 

Beneficial insects 

Wood preservatives Seed treatment 

OECD 213 Acute oral toxicity study with adult honey bees TGAI 12 

Seed treatment 

OECD 237 Acute oral toxicity study with honey bee larvae TGAI 12 OECD Draft GD 25 February 2014 

Honey bee larval toxicity test, repeated exposure4 TGAI 24 

Non-Guideline Honey bee adult chronic oral 4 TGAI 24 850.33003 or 

OECD 209 

Activated sludge, respiration inhibition test Degradates8 24 

Fate and persistence in WWTPs Down the drain assessment 

Material Preservatives Metal Working Fluids Industrial Processes and Water Systems Wood Preservatives 
Page 17 of 65

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

870.3465 90 day Inhalation TGAI 24 Human Health All Use Sites (including see

treatment) 

870.62006 90-Day Neurotoxicity TGAI 24 Human Health All Use Sites (including see

treatment) 

870.6200 Acute Neurotoxicity TGAI 24 Human Health All Use Sites (including see

treatment) 

870.78006 Immunotoxicity TGAI 24 Human Health All Use Sites (including see

treatment) 

875.1200 875.1400 

Indoor Exposure – Dermal and Inhalation 

TGAI or surrogate 24 Occupational Handler Wood Preservative 

875.1200 875.1400 

Indoor Exposure – Dermal and Inhalation 

TGAI or surrogate 24 Occupational and Residential Handler Materials Preservative – Wa

Covering Adhesive 

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

20 mg/L, then either the (i)Biodegradation in Activated Sludge Study or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activated Porous Pot Test is expected to be required. If the ASRI test EC50 is greater than 20 mg/L, then the registrant would likely be required to c

Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge U

Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to be required. Ifantimicrobial fails the Ready Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic SewActivated Sludge Units, or c) the Porous Pot study would likely be required. 

3EPA published draft guidance under guideline 850.6800 and has since published final guidance for this study under guideline 

850.3300: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0021. OECD Test Guideline 209 can also be us

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/marine ver

estuarine/marine invertebrates), as determined from the results of the acute toxicity tests (acute EC50 freshwater invertebrates; acute LC5

marine organisms; acute freshwater fish LC50). 

6All 90-day subchronic studies in the rodent can be designed to simultaneously fulfill the requirements of the 90-day neurotoxicity and/or 

by adding separate groups of animals for testing of neurotoxicity and/or immunotoxicity parameters. 

7 Specific to the following degradates: 2-mercapto-benzothiazole (2-MBT or MB) 8 Specific to the following degradates: MB and benzothiazol sulfonic acid (BTSA) 
Page 18 of 65

Table 8 – Data Needs Already Required by the 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) Triggerin

Requir

835.4200 Anaerobic Soil Metabolism 24 Environmental Fate 

Agricultural Premises and ECommercial, Institutional aEquipment Residential and Public AcceMaterials Preservatives Industrial Processes and WaWood 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 – Plants, Livestock 24 860.1500 Crop Field Trials (Honey) 24 Residue Chemistry 860.1500 Crop Field Trials (Honeycomb) 24 875.1200 875.1400 Indoor Exposure – Dermal and Inhalation 24 Occupational Handler 

Materials Preservatives (did adhesive use site in the brusscenario) Industrial Processes and WaWood Preservatives (did notreatment exposure scenario

875.1600 Application Exposure Monitoring Data Reporting This study is no longer required. This report is addressed in the submis

exposure data requirements. 

875.2800 Description of Human Activity 12 All human exposure 

Materials Preservatives Industrial Processes and WaWood 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 19 of 65

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 use in conducting the registration 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 Registration Review, also posted 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 toxicological endpoints as part of this registration 

review. Table 9 presents the endpoints used in EPA’s most recent human health risk assessment 

in support of the 2006 RED. As previously stated, toxicological studies were identified as data 

gaps in the RED and identified in the registration review as anticipated data needs based on 

currently registered uses. All available information including existing toxicology studies, valid 

scientific literature, and the studies that are expected to be required for registration review will be 

considered in establishing the endpoints to be used in the registration review 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-species 

extrapolation 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/loose 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-species 

extrapolation 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- and 

IntermediateTerm 

NOAEL=16.2 mg 

ai/kg/day MOE = 100 Developmental toxicity study in rabbits 
Page 20 of 65

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- and 

intermediateterm) 

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 characterization, 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 Sprague-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-contact pulp and paper products. Since risks of concern were not 

identified at that time and no additional uses to contribute additional exposure from food contact 
Page 21 of 65

have been registered, the agency does not anticipate the need to update the dietary (food only) 

assessment. With respect to drinking water exposure, 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 agricultural-use product (EPA Reg No. 2935-389) registered for use for 

seed treatment of rice, safflower and cotton. No additional residue chemistry 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 addressed 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 characterization of parent and/or metabolites were not 

performed and data on solvent and TCMTB concentration in the treatment solution as well as the 

seed treatment rate were not provided. In response 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, respectively. 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 identification 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, incorporated rate differences between the crops 

and applied theoretical concentration factors to the cotton TRR values 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 demonstrating that the metabolite profile in cotton 

metabolism study was stable in the extract of immature plants for ~6 months. Therefore, no 

additional storage stability data are anticipated to be needed for any crops. Additionally, since 

the only remaining active uses are rice, safflower and cotton, no field trial data for sugar beets 

are expected to be required. Furthermore, based on the negligible residues in feed items, HED 

expects negligible, if any, residues in livestock tissues; therefore, a livestock feeding study is not 

expected to be required. The only outstanding deficiency is the enforcement method. The 

available enforcement method (Method B in PAM Vol. II.) is outdated and uses toxic reagents; 

therefore, an updated enforcement method which does not use toxic reagents is anticipated to be 

required. 
Page 22 of 65

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 food-contact paper and paperboard. Acute and chronic dietary risks 

associated with this use were summarized in the 2006 RED and were below the agency’s 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 agency’s 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 conducted for TCMTB in the past. However, for 

several approved uses (including water cooling systems) the agency cannot rule out the potential 

for TCMTB to enter drinking water. There are uncertainties with respect to the residues of 

concern in drinking water, the magnitude of these 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 anticipates needing certain 

environmental fate data listed in Section 4 of this 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 drinking 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-FCID) version 2.03 (2/28/06, D324018). This 

model uses food consumption data from the U.S. Department of Agriculture’s Continuing 

Survey of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. These acute and 

chronic analyses were conservative and assumed tolerance level residues, empirical processing 

factors, 100% crop treated values for all commodities, and the FQPA Index Reservoir Screening 

Tool (FIRST) estimated peak drinking water concentration. The highest rate was from the 

safflower seed treatment scenario. The calculated acute exposure to food and water resulted in 

estimated risks which were < 2% of the acute population adjusted dose (aPAD) at the 95th 

percentile for all population subgroups. Chronic dietary 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 population subgroups, with the highest exposed 

population subgroup being children 3-5 years old at 17% of the cPAD. TCMTB is classified as 

“possible carcinogen” and the reference dose (RfD) approach should be used for quantitation of 

human risk. Therefore, quantification of risk using a non-linear approach (i.e. the chronic 

reference dose (cRfD)) will adequately protect for all chronic toxicity, including carcinogenicity 
Page 23 of 65

that could result from exposure to TCMTB. An updated dietary (food and drinking water) risk 

assessment may be conducted during registration review if the toxicological PoDs or UFs 

change, and/or updated drinking water assessment may be conducted if the values vary 

significantly from the values used in the current assessment. 

3.3 Occupational and Residential Exposures 

The agency anticipates the need to revise the Occupational Residential 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 studies that were submitted after the RED and to 

utilize the exposure and surface residue data that were required by the post-RED DCI’s and are 

anticipated to be required for registration review of TCMTB. 

3.3.1 Occupational Handler Exposure 

3.3.1.1 Antimicrobial Uses 

EPA anticipates the need to revise the occupational handler assessment conducted in support of 

the 2006 RED. The exposures assessed include 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 brush application, respectively, 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 airless sprayer application, the inhalation MOEs exceeded 1000 and 

were not of concern. Based on the low MOEs for the 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 concentration approach for inhalation 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 Registration 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 
Page 24 of 65

Scenario Exposure 

Route(s) Duration

Brush/roller application of TCMTB preserved wall 

covering adhesives 

Dermal, 

Inhalation 

Short and Intermediate 

Term 

Machinist exposure to TCMTB preserved MWF Dermal, 

Inhalation Long Term 

Wood Preservation– Dip, spray and brush 

application 

Dermal, 

Inhalation 

Short and Intermediate 

Term 

Wood Preservation – 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 exposure to TCMTB in occupational 

scenarios from handling TCMTB products during the seed treating process (both commercial and 

on-farm) and a potential for post-application worker 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 associated with the registered 

uses of TCMTB were not assessed using current HED policies. There have been updates to 

several HED standard operating procedures (SOPs) including but not limited to primary and 

secondary handler unit exposures in SOP 14 and daily pounds of seeds treated per day in SOP 

15. There is also a guidance document from the Biological and Economic Analysis Division 

(BEAD) that provides input values including seed count and seeding rate (most recently updated 

March 24, 2011). Revised occupational handler and post-application exposure and risk 

assessments will be required for registration review. These assessments will incorporate all 

updated toxicological PoDs, UFs/SFs, and all current policies and procedures. 

In accordance with the updated Part 158 data requirements (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 anticipated 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 (applicable to agricultural crops use). In 

accordance with the updated Part 158 data requirements (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 contact 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 agricultural commodities involves such an activity as 
Page 25 of 65

defined in the no/low contact criteria in the Worker Protection Standard (WPS). No quantitative 

post-application assessment is required for exposure to treated seeds that have already been 

planted. Therefore, DFR studies are not anticipated to be needed for TCMTB at this time. 

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 removed 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 that 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. Therefore, 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 through 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 residential post-application assessment conducted in 

support of the 2006 RED. Residential post-application dermal and incidental oral exposures to 

residues arising from contact with carpet and textiles (i.e. clothing and blankets) preserved with 

TCMTB were assessed using an application rate of 6000 ppm.The MOEs for carpet were 4 for 

incidental oral exposure and 2 for dermal exposure 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 concern because they did not exceed 100. 

The risks of exposure to leather products treated with TCMTB were assessed in the RED based 

upon preliminary leaching data submitted by the registrant. These data suggested that the MOEs 

would exceed 100 and thus the risks would not be of concern. 

Because of concerns identified in the 2006 RED, the textile use was deemed ineligible for 

reregistration. The post-RED DCI also required that a finalized transferable residue study be 

submitted for the leather use. This study has been submitted and will be used during registration 

review to assess the leather use. 
Page 26 of 65

The residential post application scenarios that will need to be assessed for the registration review 

of TCMTB are listed in Table 12. 

Table 12 – Residential Post-Application Exposure Scenarios for TCMTB 

Scenario Exposure Route(s) Duration

Exposure to Treated Leather Products Dermal Short and Intermediate Term 

3.3.3.2 Agricultural Uses 

There are no residential uses of TCMTB. Therefore, 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 aggregate assessment conducted in support of the 2006 

RED. Upon a reevaluation and selection of toxicological endpoints, 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 mechanism 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 produced 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 information regarding EPA’s efforts to determine which 

chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such 

chemicals, see http://www.epa.gov/pesticides/cumulative/. 

4 Environmental Risk Assessment 

The agency conducted an environmental risk assessment 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 environment was sufficiently high to pose risks to aquatic 

organisms. The highest LOC exceedance was for chronic risk to freshwater fish. LOCs also were 

exceeded for acute risks to listed and non-listed freshwater and estuarine/marine fish and aquatic 

invertebrates. LOCs were not exceeded for aquatic plants. Risks to beneficial insects and chronic 

risks to freshwater invertebrates and estuarine/marine fish and invertebrates 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 
Page 27 of 65

risk assessment planned during registration review will allow the agency to determine potential 

acute and chronic risks to aquatic and terrestrial organisms exposed to TCMTB transported from 

antimicrobial use sites into the aquatic environment. In addition, the assessment will allow the 

agency to determine potential acute and chronic risks to aquatic and terrestrial organisms 

exposed to TCMTB from the agricultural use of seed treatment (e.g., consumption of treated 

seed, consumption of plant or plant components from growing from treated seeds, contact with 

dust during planting, or runoff from fields containing treated seed). The risk assessment will 

allow the agency to determine whether each use has 'no effect' or 'may affect' federally listed 

threatened or endangered species (listed species) or their designated critical habitats. When an 

assessment concludes that a pesticide’s use 'may affect' a listed species or its designated critical 

habitat, the agency will consult with the U.S. Fish and Wildlife Service and/or National Marine 

Fisheries Services (the Services), as appropriate. 

4.1 Environmental 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 hours at pH 5. Under aerobic and 

anaerobic aquatic media, it is not stable and degrades quickly with 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-Mercaptobenzthiazole (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, including 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 the quantity of TCMTB that may reach aquatic 

environments when fallen logs are removed by floatation 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. The study was not performed according to the 

American Wood Preservers’ Association Standard, and was not conducted for 30 or 45 days but 

it provides adequate information for an environmental fate assessment of TCMTB (MRID No. 

441198-02). Table 13 below summarizes the degradates of TCMTB formed during various fate 

studies. 

Table 13 – Identification of Major Degradates of TCMTB 

Degradate Name/ 

Abbreviation 

CAS# Structure 

2-Mercaptobenzthiazole 

(MB) 

149-30-4 

N

S

SH
Page 28 of 65

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 

Thiocyanomethylthiobenzisothiazole (TCMTB) is not identified as a cause of impairment for 

any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on 

information provided at the agency’s National Pesticides Cause of Impairment of Waters website 

(searched April 10, 2014)4

. In addition, no Total Maximum Daily Loads (TMDL) has been 

developed for TCMTB based on information provided at the agency’s National Pesticide 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. 

4.2 Environmental Exposure Pathways 

Aquatic organisms potentially at risk from exposure 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 preservatives, and those inhabiting water bodies 

receiving runoff from fields planted with treated seed. Water bodies might include impounded 

bodies (e. g., ponds, lakes, reservoirs) or flowing waterways (e. g., streams, rivers). For uses in 

coastal areas, aquatic habitat also includes marine ecosystems, including estuaries. Aquatic 

organisms likely to be acutely or chronically exposed include fish, invertebrates, and aquatic 

stages of amphibians. For aquatic animals, the major route of exposure is considered to be 

uptake via the respiratory surface (gills) or the 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. 

 

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

S

S

N

S

N

S

OH

N

S

SO3H
Page 29 of 65

Terrestrial organisms potentially at risk from exposure to TCMTB or its degradates include, but 

are not limited to, those consuming or contacting treated seed on the field, those drinking water 

(puddles) on the treated fields, or those contacting, inhaling, or consuming dust occurring during 

mechanical planting of treated seed. In addition, TCMTB may move off-field through dust/drift 

during planting or runoff after planting and potentially contact non-target seeds and plants. 

All U.S. rice is produced in irrigated fields. Producers in the United States can apply seed 

aerially in dry or flooded fields, or drill or broadcast 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 typically begins in early 

March in Texas and southwest Louisiana. The Delta plants the bulk of its crop in April, and 

California's crop is planted from late April through 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. Some producers in Texas and southwest Louisiana 

are able to reflood their fields after harvest and achieve a partial 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 USEPA 2014). 

4.3 Ecological Effects Assessment 

4.3.1 Ecotoxicology Endpoints

4.3.1.1 Submitted Data 

Acute and chronic toxicity data from registrant-submitted studies conducted in accordance with 

the 850 OCSPP Harmonized Test Guidelines will be used to evaluate the potential effects of 

TCMTB to plants and animals. All available ecotoxicity endpoints from studies submitted by 

registrants are tabulated in Appendix C. The most sensitive endpoints 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 data are anticipated to be needed to assess risks 

to beneficial insects from use of TCMTB to treat wood. Acute toxicity data for the passerine are 

anticipated to be needed as passerines are often more sensitive than upland game birds or 

waterfowl. Additional honey bee toxicity 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 
Page 30 of 65

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 EC50

NOAEC 

EC50 = 2.7 μg ai/L 

NOAEC = 1.5 μg ai/L 48721501 

Aquatic vascular plants TGAI EC50

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 additional 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 the Seventeenth Annual Aquatic Toxicity Workshop 

(Chapman et al. 1991) and a summary of a thesis entitled The Effect of TCMTB on Juvenile Coho 

Salmon (Oncorhynchus kisutch): Sublethal Toxicity Testing. These studies demonstrated that 

sublethal exposure to TCMTB caused gill damage and behavioral changes, including swimming 

performance, which could reduce the ability of fish 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 determine the estimated environmental concentration 

(EECs) in the aquatic and terrestrial environment. Resulting exposure estimates will be 

compared to the toxicity endpoints to determine if levels of concern are exceeded for each 

receptor group. 
Page 31 of 65

4.4.2 Screening Level Down-the-Drain Analysis 

The Down-the-Drain (DtD) module of E-FAST (Exposure 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 degradates. 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 parameters 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 wastewater treatment was used in DtD model 

runs. 

The DtD analysis for TCMTB is intended to serve 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 potential exposures based on the assumptions 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 lowest maximum annual WWTP influent volumes of 

TCMTB that would trigger potential concerns for aquatic organisms downstream of domestic 

WWTPs. 

Table 15 presents results of a screening-level DtD analysis for TCMTB which is based on 

laboratory toxicity data for freshwater 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 concentration of concern (COC) for endangered freshwater 

fish and invertebrates. 

Table 15 - Summary of Screening Level Down-the-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 

 (COC = 1.1 

ug/L) 

Endangered 

speciesAquatic plants

(COC=1.5 

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 
Page 32 of 65

 

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)

Endangered 

speciesAquatic 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 TCMTB is released to domestic wastewater treatment 

plants. Based on registered uses of TCMTB presented in Table 8 of this PWP, there are some 

uses, such as commercial and industrial cooling water systems and paper mill water systems, for 

which discharges may enter industrial WWTPs rather than domestic WWTPs prior to entering 

surface water. Different methods and tools for assessing potential exposures and associated 

ecological risks will be applied for these other types of uses. 

There is considerable uncertainty regarding the 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 entering industrial wastewater treatment plants as a 

result of industrial uses of MCMTB. The Agency does not have high quality data on the toxicity 

of TCMTB to activated sludge microorganisms in wastewater treatment plants and does not have 

high quality data on biodegradation of TCMTB during wastewater treatment. Consequently, the 

agency anticipates needing the following data on TCMTB to fulfill data gaps regarding toxicity 

to activated sludge microorganisms and biodegradation of TCMTB during wastewater treatment: 

1. Activated Sludge Respiration Inhibition (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 literature studies will be 

identified through EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will 

be searched during the risk assessment phase and the data reviewed following the agency’s 
Page 33 of 65

policy for reviewing public literature for use in assessing risks from pesticides6. 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 USEPA, Office of Research and Development, 

and the National Health and Environmental Effects Research Laboratory's Mid-Continent 

Ecology Division. 

5 Endocrine Disruptor Screening Program (EDSP) 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of the 2006 RED for TCMTB, EPA reviewed these data and selected 

the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard 

database. However, as required by FFDCA section 408(p), TCMTB is subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP). 

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

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

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

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

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

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

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

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

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

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

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

Under FFDCA section 408(p), the agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 20137

 and includes some pesticides 

 

6

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_reregistration_work

group/esa_evaluation_open_literature.htm 7

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

chemicals. 
Page 34 of 65

scheduled for registration review and chemicals found in water. Neither of these lists should be 

construed as a list of known or likely endocrine disruptors. 

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.8

6 Optional Label Changes 

The agency invites comment on any label amendments that could be considered to eliminate the 

anticipated need for EPA to require certain data, reduce the possibility that EPA’s planned risk 

assessments overestimate risk due to reliance on conservative assumptions, and/or improve label 

clarity. 

7 Guidance for Commenters 

7.1 Preliminary Work Plan 

The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the TCMTB registration review case. 

7.1.1 Trade Irritants 

Through the registration review process, the agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The agency 

will work to harmonize tolerances and international maximum residue limits (MRLs) and may 

modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any 

trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and 

MRLs in key export markets, providing as much specificity as possible regarding the nature of 

the concern. 

7.1.2 Water Quality 

The agency invites submission of water quality data for this pesticide. To the extent possible, 

data should conform to the quality standards in Appendix A of the OPP Standard Operating 

Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s 

Registration Review Risk Assessment and Management Process9 in order to ensure they can be 

used quantitatively or qualitatively in pesticide risk assessments. 

7.1.3 Environmental Justice 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

 

8

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

9 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
Page 35 of 65

environmental justice issues, the agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to TCMTB compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population.

7.1.4 Structure Activity Relationships 

EPA must rely upon information of appropriate quality and reliability for each decision made by 

the agency. In the OPP, the evaluation process for a pesticide chemical traditionally begins with 

the applicant’s submission of a set of studies conducted with the specific pesticide chemical of 

interest. The use of the results of such testing (measured data) is a logical, scientifically rigorous 

process that identifies the physical, chemical, and environmental fate properties of the pesticide, 

as well as the dose and endpoints at which an adverse effect can occur in various animal species. 

Today, there is significant interest in alternative techniques, i.e., techniques other than data 

generation that could significantly inform the agency’s decision-making process. Recently, OPP 

has made increasing use of structure activity relationship (SAR) as part of its regulatory 

decision-making process. In the SAR process, a chemical's molecular structure is compared to 

that of other chemicals for which data are available. These structural similarities are then used to 

make predictive judgments about a chemical’s physical, chemical, and biological properties. 

Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly 

related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To 

develop a QSAR, a selected set of measured data on a single physical, chemical, or biological 

property is used to derive a model (an equation) to predict the value of that property. 

Since SAR assessments and QSAR modeling are another set of tools that are available to agency 

scientists, OPP has begun a process shift that envisions shifting from the current study-by-study 

approach to an approach in which the use of predicted data, generated using validated models, is 

considered along with information from open literature and studies specifically generated under 

Part 161 requirements. All relevant information would be considered as part of a weight-of-theevidence evaluation. 

At this time, EPA believes that for certain endpoints, especially physical/chemical and fate 

properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements 

for many antimicrobial pesticide chemicals. When considering biological properties, at this time, 

EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of 

chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is 

appropriate because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a 

screening-level assessment procedure rather than multiple tiers of assessments with progressively 

more data requirements. 

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the 

TCMTB case, then the agency invites submission of this information. The submitter would be 

expected to supply a rationale describing the utility of the information and provide 

documentation on the scientific validity of the information. The determination that the predicted 

data fulfills the data requirement would be at the sole discretion of the agency. Pre-submission 

consultation with the agency is encouraged. 
Page 36 of 65

7.1.5 Additional Information 

Stakeholders are also specifically asked to provide available information and data that will assist 

the agency in refining its risk assessments, including any species-specific ecological effects 

determinations. The agency is interested in receiving the following information: 

1. Confirmation on the following label information: 

A. Sites of application 

B. Formulations 

C. Application methods and equipment 

D. Maximum application rates 

E. Frequency of application, application intervals and maximum number of 

applications 

F. Geographic limitations on use 

2. Use or potential use distribution 

3. Use history 

4. Usage/use information for non-agricultural uses (e.g., materials preservation) 

5. Typical application interval 

6. State or local use restrictions 

7. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the agency 

8. Monitoring data 

8 Next Steps 

After the 60-day comment period closes in November, 2014, the agency will review and respond 

to any comments received in a timely manner, and then issue a Final Work Plan for the TCMTB 

case. 
Page 37 of 65

9 References 

C. Smith D324013. TCMTB [2-(Thiocyanomethylthio)benzothiazole]: Second Revision of 

the Occupational and Residential Exposure Assessment for the Reregistration 

Eligibility Decision Document. 7/27/2006 

D. Smegal D322597. TCMTB Risk Assessment for the Reregistration Eligibility Decision 

(RED) Document 8/01/2006 

EPA 2006a. Registration Eligibility Decision for 2-(Thiocyanomethylthio) benzothiazole 

(TCMTB), F. Sanders, Antimicrobials Division, August 1, 2006. 

EPA. 2006b. Environmental fate assessment of 2-(Thiocyanomethylthio) benzothiazole 

(TCMTB) for the Reregistration Eligibility Decision (RED) Document. S. 

Gowda, Antimicrobials Division, February 16, 2006. 

EPA, 2006c. Occupational and Residential Exposure Assessment for 2-(Thiocyanomethylthio) 

benzothiazole TCMTB. DP 322615, S. Mostaghimi, Antimicrobials Division, 

April 19, 2006 

Kline, 2005. Specialty Biocides North America 2004-2005, Volume II: United States, Kline and 

Company, Inc. 

Manninen, A., Auriola S, Vartiainen M., Leisivuori J., Turunen, T., Pasanen M. 1996. 

Determination of urinary 2-mercaptobenzothiazole (2-MBT), the main metabolite 

of 2-(thiocyanomethylthio)benzothiazole (TCMTB) in humans and rats. 

S. Ary D322617. TCMTB. Summary of Analytical Chemistry and Residue Data for the 

Reregistration Eligibility Decision (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, 

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for Weed Control in Rice Production (DP # 420989). Memo from Biological and 

Economic Analysis Division (7503P) to Pesticide Re-evaluation Division 

(7508P); August 20, 2014. U.S. Environmental Protection Agency, Office of 

Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, 

Biological and Economic Analysis Division, Washington, DC. 

T. Bloem D418804. TCMTB. Review of Cotton Metabolism Study Submitted in Response 

to Deficiencies Identified in the TCMTB ((2-benzothiazolylthio)methyl 

thiocyanate) Reregistration Eligibility Decision (RED) Document. 8/26/2014 
Page 38 of 65

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 Hypersensitivity (Buehler Technique) of 

TCMTB: Intox Sample No. 513: Protocol No. BUC-AT-046. Unpublished study 

prepared by Intox Laboratories, 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 Other Genotoxic Effects TCMTB (EPA Reg. 

No.:1448-29): In the Rat Primary Hepatocyte Unscheduled DNA Synthesis 

Assay: HBC Project No. 20991. Unpublished study prepared by Hazleton 

Biotechnologies Company. 21 p. 

00165520 Bonner, G. (1986) Evaluation for Structural 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 study 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 study 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 Research International Limited. 10 p. 

41342201 Goburdhun, R.; Greenough, R. (1988) 2-(Thiocyanomethylthio) Benzothiazole 

(TCMTB) 52 Week Dietary Toxicity Study in Dogs: Lab Project No. 635605; 

Report No. 5646. Unpublished study prepared by Inveresk Research International. 

160 p. 

41386101 Lawlor, T.; Respess, C. (1990) Mutagenicity 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) TCMTB Two Generation Reproduction Study in 

Rats: Report No. 5168: IRI Project No. 435334. Unpublished study prepared by 

Inveresk Research International. 156 p. 
Page 39 of 65

41515401 Hazleton-Institut Francais de Toxicologie (1990) TCMTB Technical Grade: 

Acute Dermal Median Lethal Dose: 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 Inveresk Research International. 247 p. 

41570301 Finch, J. (1990) TCMTB--104 Week Dietary 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 Irritation 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. Unpublished study prepared by Springborn 

Laboratories, Inc. 63 p. 

41640601 Terrill, J. (1988) Acute Inhalation Toxicity Study with TCMTB in the Rat: Lab 

Project Number: 197/188. Unpublished study pre- pared by Hazleton Laboratories 

America, Inc. 53 p. 

41655801 Siglin, J. (1990) 21-Day Dermal Toxicity 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 After 104 Weeks): Supplement: Lab Project 

Number: 435313. Unpublished study prepared by Inveresk Research 

International. 1160 p. 

42349201 Karcher, R.; Siglin, J.; Becci, P. (1986) 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 Carcinogenicity Study in Mice: ?Final Report|: 

Lab Project Number: 435329: 7516. Unpublished 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 14C-TCMTB by Bluegill Sunfish Leopmis macrochirus. 

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

Laboratories International, Inc. 
Page 40 of 65

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 Active Ingredient TCMTB. Project 

Number: B/0456/9. Unpublished study prepared by Opus Prima S.A. 39 p. 

46947216 Bernardo, W. (1999) Bacterial Reverse Mutation Test Synopsis and Toxicity 

Category Recommendation Technical Grade Active Ingredient TCMTB. Project 

Number: B/0459/9. Unpublished study prepared by Opus Prima S.A. 12 p. 

46947217 Richiello, G. (2005) "In Vitro" Mammalian Cell Gene Mutation Test Study 

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. 

46947218 Richiello, G. (2005) Unscheduled DNA Synthesis in Mammalian 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 Raltech Scientific Services. 438 p. 
Page 41 of 65

Appendix A Toxicology Profile 

Acute Toxicity for Product Labeling 

The data base for acute toxicity is considered complete. No additional studies are expected to be 

required at this time. TCMTB exhibits low acute oral and dermal toxicity (toxicity category III). 

However, it is highly irritating to the eyes and skin (toxicity category I and II, respectively)) and 

is also considered to be highly toxic via the inhalation route of exposure (toxicity category I). 

TCMTB is a dermal sensitizer. The acute toxicity data on the TCMTB Technical (80% ai), or 

Busan 72 (containing 60% ai) are summarized below in Table A1. 

Table A1 – Acute Toxicity Studies for TCMTB 

Guideline No./ Study 

Type MRID No. Results Toxicity Category

870.1100/ 

Acute oral toxicity 41583801 LD50 = 750 mg/kg (M+F); 80% ai III 

870.1200/ 

Acute dermal toxicity 41515401 LD50 > 2000 mg/kg (M+F); 80% ai III 

870.1300/ 

Acute inhalation toxicity 41640601 LC50=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 induced 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 considered adequate for risk assessment purposes. 

Although the subchronic rodent studies 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, TCMTB caused increased incidence of mild to severe 

stomach lesions characterized by inflammation, hyperplasia, necrosis, and ulceration. 

Inflammatory cells infiltration and edema were also noted at a low incidence. TCMTB resulted in 

decreased body weight gains (78 to 84% of control), food consumption (87-95% of control) and 

food efficiency. In a 21-day rat dermal toxicity study, TCMTB produced dose-dependant dermal 
Page 42 of 65

irritation in all dose groups beginning on treatment days 3-4, which progressed to eschar formation. 

Rats in the mid and high dose group had ulcers, hemorrhages and chronic dermatitis. Decreased 

body weight gain, food consumption, and hematological (changes in hemoglobin, hematocrit, and 

segmented neutrophils) and clinical chemistry changes (blood urea nitrogen, glucose, globulins, 

and elevated serum aspartate aminotransferase (AST) were also noted. However, the clinical 

chemistry changes did not correspond to any treatment-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 rats (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 equivalent 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 (24.5 mg ai/kg/day) and above in the form of 

increased incidence of squamous epithelial hyperplasia 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 efficiency (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/day (24.5 mg ai/kg/day) and the NOAEL for systemic toxicity is 

10 mg TCMTB/kg/day (8.3.8.4 mg ai/kg/day) based on increased incidences of stomach lesions. 

This 90-day oral toxicity study in the rat is UNACCEPTABLE-GUIDELINE and does not 

satisfy the guideline requirement for a subchronic (90-day) oral toxicity study OPPTS 870.3100 

in the rat because is was only a range finding study, and based on major deficiencies (stability, 

diet concentrations and homogeneity were not measured, and hematology and clinical chemistry 

parameters were not measured). This study can not be upgraded. Although this study is 

unacceptable, there are chronic studies available to fulfill the guideline requirements. No 

additional oral toxicity data are anticipated 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) was 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/day, which is equivalent to 0, 13.4, 20 and 

30 mg ai/kg/day, respectively based on a purity 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 the 
Page 43 of 65

high dose group. Mild to severe changes in the 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) and 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 toxicity study in the rat is UNACCEPTABLE-GUIDELINE and does not 

satisfy the guideline requirement for a subchronic (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 ophthalmoscopic examinations were not 

done. The approximate purity of 80% ai was submitted 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 anticipated to be required at this time. 

870.3200 21-Day Dermal Toxicity - Rat 

Executive Summary: In a dermal toxicity 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 beginning 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 were observed in male and female rats of the 

high dose level. Several clinical chemistry parameters were significantly increased in high dose 

males and females (blood urea nitrogen, glucose and globulins); while high dose females also had 

elevated serum aspartate aminotransferase (AST). However, the clinical chemistry changes did 

not correspond to any treatment-related 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 LOAEL is 20.6 mg ai/kg/day based 

on dose-dependent irritation which progressed to eschar formation in 2 rats of the low dose group 

and in all rats of the mid- and high-dose groups. Mid- and high-dose groups exhibited ulcers, 

hemorrhages and chronic dermatitis. 

Based on the recent submission of purity information 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. 
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Developmental Toxicity 

The data base for prenatal developmental toxicity is considered complete. Developmental 

toxicity studies were available in both the rat and rabbit for 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 and 64 mg ai/kg/day. No 

developmental effects were noted in the rabbit at the highest dose tested (32 mg ai/kg/day). 

However, in the rat adverse developmental effects including increased fetal and litter incidence of 

fused/wavy ribs, rudimentary cervical, thoracic and lumbar ribs and increased incidence of 

sternebrae and pelvic girdle anomalies were noted at doses of 105 mg ai/kg/day, which was 

maternally toxic. Thus, the Agency concludes that these studies show no evidence of primary 

developmental toxicity of TCMTB, which is consistent with the previous conclusion of the Health 

Effects Division’s 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 dissolved in corn oil/ 1% Tween 80 at doses of 0, 

25.1, 76.5, and 125.5 mg/kg/day from gestation days 6 through 15. These 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 ventral alopecia, rough coat, dyspnea/wheezing, oral 

discharge, nasal discharge, diarrhea/loose stool, urine staining, piloerection, and hunched gait. 

Developmental toxicity was evident at the 105 mg ai/kg/day (125.5 mg TCMTB/kg/day) dose level 

in the form of increased fetal and litter incidence of fused/wavy ribs, rudimentary cervical, 

thoracic, and lumbar ribs, and increased number of sternebrae and 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 increased fetal and litter incidence 

of skeletal anomalies. 

This developmental toxicity study in the rat is classified as ACCEPTABLE-GUIDELINE and 

satisfies the requirement (OPPTS 870.3700) for a developmental toxicity study in the rodent. No 

additional studies are anticipated to be required at this time. 

870.3700b Prenatal Developmental Toxicity Study - Rabbit

In a prenatal developmental toxicity (teratology) 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 verified by the registrant. 
Page 45 of 65

Maternal toxicity was evidenced by decreased body weight gain and food consumption in the 32 

mg ai/kg/day dose group. Statistically 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 considered 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 aborted their litters prior to scheduled sacrifice (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 occurring 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/day based on decreased body weight gain and food 

consumption. 

No statistically significant or treatment-related changes were noted in any treatment group for 

deaths/resorptions, altered growth, developmental anomalies or malformations. The 

Developmental Toxicity LOAEL is greater than 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 toxicity (teratology) study in rabbits. No additional studies are 

anticipated to be required at this time. 

Reproductive Toxicity 

The data base for reproductive toxicity is considered complete. No additional studies are 

required at this time. The available data showed that TCMTB did not cause reproductive effects 

in rats. 

In a 2-generation reproduction toxicity study (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 levels 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 significant effects were noted in mean body weight in the high dose 

offspring in the second mating (F2B) around lactation day 21 (approximately 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 toxicological significance. 
Page 46 of 65

The parental/systemic NOAEL = 400 ppm (38.4/45.5 mg /kg/day [males/females]) and the 

parental/systemic LOAEL > 400 ppm (> 38.4/45.5 mg /kg/day [males/females]). The offspring 

NOAEL is 400 ppm (HDT) and the offspring LOAEL > 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 study (§870.3800; OECD 416) in rats 

Consistent with both the RfD Peer Review’s conclusion and that of the California Environmental 

Protection Agency’s summary of TCMTB (February 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 considered complete, and no additional studies are required 

at this time. 

In a chronic toxicity study (MRID 41342201), technical TCMTB (81.6% ai, Batch 1517; MRID 

92179008, 46698604) was administered to male and female beagle dogs at dose levels of 0, 

100ppm (3.8 mg/kg/day in males; 4.0 mg/kg/day in females), 300ppm (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 and female dogs at the 1000 ppm dose level. 

Hematological effects include significant decreases in circulating white blood cells and 

monocytes in male dogs at all dose levels tested, while effects on hematology in female dogs 

were limited. Plasma ALT was significantly decreased 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 were observed in female dogs. Involution of the 

thymus was the main histologic finding, and the severity of this lesion appeared 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 plasma 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. However, this study is scientifically 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 considered complete, and no additional studies are 

anticipated to be required at this time. TCMTB produced an increase in testicular interstitial 
Page 47 of 65

adenomas in male rats and thyroid C-cell adenomas in female rats. 

Combined Chronic Toxicity/Carcinogenicity Study in Rats (MRID No.: 42116301; 41529701; 

41570301) 

In a combined chronic/carcinogenicity 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, interim 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 toxicity were noted during the study. No dose-related or significant 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 platelets was noted in all treated females at week 104. All other 

changes in hematology parameters were not considered to be toxicologically significant. No 

changes in the clinical chemistry parameters were considered to be biologically significant due to 

the lack of a dose—response relationship. No treatment—related 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 dose response relationship was not present, it was 

not considered to be biologically significant. Terminal organ weights were not reported. 

Only one finding displayed a dose-response relationship in the microscopic pathology, interstitial 

cell tumors in the testes. The tumor incidences were control group 4/50, low dose 5/50, mid dose 

13/50 and the high dose with 14/50. The mid and high doses were significantly different 

(p<0.05) from the controls. Additionally, the incidence of thyroid C-cell adenomas was increased 

in female rats of the high dose group, as compared 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 interstitial cell tumors in the testes 

and thyroid C-cell adenomas in female rats. 

Although the current study did not appear to test to high enough doses to produce systemic toxicity, 

on the basis of results from other toxicity 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 anticipated to be required at this time. 

Discussion of Tumor Data 

Two findings displayed dose-response relationships in the microscopic pathology, interstitial 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 interstitial cell tumors. 

Female rats had significant dose-related increasing trends, and significant differences in the pairwise comparisons of the 20 mg/kg/day dose group with the controls for thyroid C-cell adenomas 
Page 48 of 65

and adenomas and/or carcinomas combined; however, only adenomas were present in treated 

groups (the control group had the single carcinoma noted). Although there were no significant 

differences in the pair-wise comparisons of the dosed groups with the controls, female rats did 

have a significant increasing trend in thyroid C-cell hyperplasia at p < 0.01. 

Adequacy of the Dose Levels Tested 

The statistical evaluation of mortality indicated no significant incremental changes with 

increasing doses of TCMTB in male rats. Female rats showed a significant decreasing trend in 

mortality with increasing 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 platelets was noted in all treated females at week 104. All other 

changes in hematology parameters were not considered to be toxicologically significant. No 

changes in the clinical chemistry parameters were considered to be biologically 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 considered 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 control 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) indicate that toxic effects (decreased body weight gain and 

increased incidence of squamous epithelial hyperplasia of the stomach) were observed at the dose 

level of 30 mg/kg/day (a dose slightly higher than the HDT in this 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 rats (MRID#’s 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 give 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 gains in high dose males and females 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 was no effect on food consumption in this study. 

None of the gross findings were remarkable. An increase in focal and diffuse hyperplasia of the 
Page 49 of 65

duodenal mucosa was seen microscopically in males receiving 150 mg/kg/day: the incidence was 

10/42 compared to 1/41 in controls (p<0.01). A nonsignificant increase was seen for mucosal 

hyperplasia of the duodenum in high-dose females (8/45 compared to 4/46 in controls). No other 

pathologic findings were considered 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 duodenum 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 tumors observed in male or female mice. All tissues were 

examined. 

Adequacy of the Dose Levels Tested 

The statistical evaluation of mortality indicated no significant incremental changes with 

increasing doses of TCMTB in male mice. Female mice showed a significant decreasing trend in 

mortality with increasing 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 weeks 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 controls for the high-dose males and females, 

respectively. No marked effects on food consumption were observed. None of the gross 

findings were remarkable. Based on the histologic changes in the duodenum in high-dose males 

and the decreased weight gain in both sexes at the high-dose, the systemic 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 considered 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-of-the-evidence on 2-(Thiocyanomethylthio) 

benzothiazole (TCMTB) with particular reference to its carcinogenic 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 
Page 50 of 65

that for the purpose of risk characterization, the Reference Dose (RfD) approach should be used 

for quantitation of human cancer risk. 

Mutagenicity 

The data base for mutagenicity is considered adequate and no additional studies are anticipated 

to be required at this time. TCMTB was negative for mutagenicity in the gene mutation assay 

with bacteria (MRID# 41386101), and did not cause 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 genotoxicity 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 confirmed in an independently performed trial. 

Study Type: Evaluation for Structural Chromosomal Aberration of TCMTB (EPA Reg. No.: 

1448-29): Clastogenic Evaluation in the In Vivo Mouse Micronucleus Assay 

In a structural chromosomal aberration assay (MRID# 00165520), the high dose of 

TCMTB (500 mg/kg) exhibited mortality and signs of clinical toxicity. No evidence of an 

increase in micronucleated polychromatic erythrocytes was noted at the 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 primary hepatocytes as measured in this study. 

Immunotoxicity 

There is no immunotoxicity database for TCMTB. The agency anticipates the need to require an 

immunotoxicity study for registration review. 

Neurotoxicity 
Page 51 of 65

There is no neurotoxicity database, acute or subchronic, for TCMTB. The agency anticipates the 

need to require a 90-day neurotoxicity study for registration review. 

 

Other Toxicological Effects 

2-Mercaptobenzothiazole (2-MBT) is the main mammalian urinary metabolite of TCMTB, and 

has been suggested as a biological marker of exposure 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 samples, 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-(mercaptomethylthio)benzothiazole. The amount of 

2-MBT excreted in rat urine was 66  12% (SD), 51 20% and 44  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 workers. Most concentrations of 2-MBT were below 

the limit of detection, 0.12 mol/l, the concentrations were 0.12-0.15 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 workers’ 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 radioactivity was monitored, as well as measurement of 

plasma levels and excretion of TCMTB derived radioactivity in bile. Metabolites of TCMTB in 

urine, plasma, and bile were characterized using 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 radioactivity. However, these levels were low (0.02-2.41 g equiv./g 

tissue). Measurement of elimination of radioactivity from blood showed that the half-life in red 

cells might be in excess of 7 days. 

Excretion of TCMTB derived radioactivity was mainly in urine, with between 80-85% of the 

total dose excreted in non-cannulated rats. Fecal excretion 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 order elimination at both the low and high dose. 
Page 52 of 65

Metabolite characterization using 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 metabolite could be a glucuronide conjugate. 

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. 

 
Page 53 of 65

Appendix B Environmental Fate 

Environmental Fate and Transport Properties of TCMTB and 

Degradates 

Hydrolysis 

In a hydrolysis study conducted under abiotic and buffered conditions, 2-(thiocyano 

methylthio)benzothiazole (TCMTB), appeared hydrolytically 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  for up to 35 days (pH 5 and pH 7) or for 21 days at 

pH 9. The major degradate of 2-mercaptobenzothiazole (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, degradation of TCMTB was noted at pH 9 with a half -life of 1.8 days. 

The second study was also conducted under abiotic and buffered conditions.(MRID Nos. 

423861-01 and MRID No. 434376-01). The studies were accepted as supplemental and no 

additional data is anticipated to be required (161-1). 

Aqueous Photolysis 

Since the hydrolysis study showed that TCMTB was stable at pH 5 only, a photodegradation 

study was conducted in a pH 5 buffered aqueous solution, which was irradiated over an 8-hour 

period with artificial light at 25, TCMTB degraded with a half-life of 1.5 hours. The dark 

control solution showed that TCMTB was stable. Main degradation products were: MB (75.1%) 

of the applied radioactivity following 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. 426309-01). 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 indicates that a chemical may potentially 

bioconcentrate; however, the results of a bioconcentration 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 sunfish under flow-through aquarium 

conditions. Analysis of fillet, whole fish, and visceral portions were performed throughout the 

exposure period. Maximum bioconcentration factors (BCFs), based on total radioactivity, were 

302X for viscera, 64X for fillet, and 184X for whole fish tissues. The maximum concentrations 

of residues were 27 g/kg (14 days) for the fillet tissue, 130 g/kg (28 days) for the viscera 

tissue, and 79 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, 
Page 54 of 65

viscera and whole fish tissues, respectively, and 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 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 day one after the twenty eight day study. The Agency concludes 

that since the depurated residues 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, residues were characterized in the viscera and 

fillet tissues collected at 21 and 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, respectively. Three unidentified minor metabolites were 

each present in the fillet tissues at 2.3 ppb, and five unidentified minor metabolites were each 

present in the viscera tissues at 9.1 ppb levels. The results of the two studies strongly indicate 

that though some residues were characterized, 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 quantitation (LOQ). The study is acceptable and fulfils the 

fate data requirements (MRID 42418501) and no additional 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 post-treatment. In the aqueous 

phase, the major degradate of MB was present at a maximum of 23.6% of the applied 

radioactivity at 31 days post-treatment. An unidentified major degradate 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 [14C] 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 guidelines for the fulfillment of data requirements 

(OPPTS 162-4) on aerobic aquatic metabolism because the degradate that reached 30.5% was 

not identified. This study is acceptable/supplemental (MRID No. 425086-01). No additional data 

are anticipated to be required. 

Anaerobic Aquatic Metabolism 

A study of the anaerobic metabolism of TCMTB in lake water and sediment was also conducted. 

Samples of lake water and sediment were incubated at 25 ± 1C for up to 58 days. In this study, 

TCMTB degraded (calculated half-life = 2.7 days) under anaerobic aquatic conditions to two 

major degradates, MB and DBB. DBB was present at a maximum of 67.7% of the applied 

radioactivity at 14 days post-treatment; MB was at a maximum of 30.8% 58 days post-treatment. 

Other minor degradation products were also found. The majority of the residues were observed 

in the water phase. This study satisfies the anaerobic aquatic metabolism guideline requirements 

(OPPTS 162-3) (MRID No. 428154-01) and no additional data are anticipated to be required. 
Page 55 of 65

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, clay and clay loam. The study determined 

TCMTB to be very mobile in clay loam, sand, and sandy loam soil, and mobile in clay and silt 

loam soil. Freundlich Kads 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 Koc

values were 282, 765, 2120, 2554, and 7896 mL/g. Freundlich Kdes 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 Koc values were 262, 1480, 1627, 1504, and 9973 mL/g. This study 

satisfies the adsorption/desorption guideline 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 maintained 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-benzothiazolol (BTOL), 

benzothiazol sulfonic acid (BTSA), DBB, and seven other minor unidentified metabolites. The 

major degradate BTSA was present at a maximum of 70.8% of the applied 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 satisfy guidelines (OPPTS 162-1) for aerobic soil 

metabolism (MRID No. 435322-01). The agency however, 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 degradates are presented in the table below. These 

are estimated characteristics based on EPA’s EPI Suite Estimation Program ,version 4.3. 

(accessed on April 10, 2014). 

Table B1: P/Chem and Some Fate Characteristics of Degradates 
Page 56 of 65

NameCas# mp/bp/ 

(

o C) 

Vapor 

pressure 

(mm Hg) 

Solubility in 

water 

(mg/L) 

Log 

Kow

Ready 

biodeg. 

Half life in air 

(hours) 

STP 

Removal 

(%) 

Koc 

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 x104

The estimated characteristics of the degradates of TCMTB show that the solubility of these 

degradates appear to vary from highly slightly to very little soluble in water. All degradates have 

low vapor pressure and are not likely to volatilize from surface water. Once in air their half lives 

in the air vary between 24 minutes to three hours to about three days, and are not possibly 

persistent in the atmosphere. The log Kow 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 Koc less than 3 to 129 L/Kg indicating that these 

degradates are mobile to not mobile from soil surfaces. Again the dithio has a very high value of 

Koc of > 1 x104

 L/Kg, which makes it immobile from the soil surfaces. 

Environmental Fate Data Requirements for the Degradates of TCMTB. 

At this time the agency anticipates the need to require the following studies for the two 

degradates, 2-Mercaptobenzthiazole (MB), and Benzothiazol sulfonic acid (BTSA): 

 Activated Sludge Respiration Inhibition (OECD 209) or Modified Activated Sludge 

Respiration Inhibition (OCSPP 850.6800); 

 Ready biodegradability test (835.3110) or one of three biodegradation in activated sludge 

simulation tests (835.3220; 835.3280; 835.3240) 

 
Page 57 of 65

Appendix C Ecotoxicology Profile 

Toxicity to Terrestrial Organisms 

Birds, acute and dietary 

One available acute-oral study categorizes technical-grade TCMTB as being slightly toxic to 

birds and another categorizes a major degradate (2-MBT) as being practically nontoxic. The 

guideline (850.2100) is satisfied. Three dietary studies indicate that TCMTB is practically 

nontoxic and 2-MBT as slightly to practically nontoxic 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 (850.3020, 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 categorize technical-grade TCMTB as being very highly 

toxic to freshwater fish. One additional study indicates that the degradate 2-MBT is highly toxic. 
Page 58 of 65

The guideline (850.1075) for acute toxicity testing is satisfied. The two available chronic studies 

indicate that TCMTB impacts reproduction, growth, and survival at low concentrations. The 

guideline (850.1400) for freshwater chronic 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 categorize technical-grade TCMTB as being very 

highly toxic to freshwater invertebrates. An additional study with 2-MBT categorizes this 

degradate as being moderately toxic. The guideline (850.1010) for acute toxicity testing is 

satisfied. The one available chronic study indicates that TCMTB impacts reproduction, growth, 

and survival at low concentrations. The guideline (850.1300) for freshwater chronic testing is 

satisfied. No additional data are anticipated to be required. 
Page 59 of 65

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 TCMTB as being very highly toxic 

to estuarine/marine organisms. The guidelines for acute testing with fish ((850.1075), a bivalve 

(850.1025 or 850.1055), and mysid (850.1035) are satisfied. 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-stage) and mysid (850.1350) are not satisfied. 

Because TCMTB degrades rapidly in the environment, most chronic exposure is anticipated to 

be to the degradates. Therefore, the chronic testing is anticipated to be needed for 2-MBT, a 

major degradate in the water column. 
Page 60 of 65

Toxicity to Estuarine/marine 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 vascular species and four studies for non-vascular species. The data 

indicate that aquatic plants are highly sensitive to exposure to TCMTB. The guidelines for 

testing with a vascular species (850.4400), three algal species (850.4500), and cyanobacteria 

(850.4550) are satisfied. No additional data 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 

48721502 

Acceptable

Marine diatom 

(Skeletonema costatum) TCMTB (81.839) EC50 = 2.7 

NOAEC = 1.5 

48721501 

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 

Acceptable 

Benthic Organisms 
Page 61 of 65

Based on environmental fate properties (i.e., Kd >50 L/kg for silt loam soil; Koc’s >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, and mortality in the vegetative vigor test. Phytotoxic 

effects were also demonstrated in the seedling emergence test and included leaf curl, chlorosis, necrosis, 

and mortality. For vegetative vigor, the most sensitive monocot species, based on biomass, was corn with 

a NOAEC of 0.6 lb ai/A and an EC25 of 0.79 lb ai/A, and the most sensitive dicot species was soybean, 

based on survival, with a NOAEC and EC25 values of <0.25 and 0.37 lb ai/A, respectively. For seedling 

emergence, the most sensitive monocot species was corn, based on biomass, with NOAEC and EC25

values of 3.36 and 23.15 lb ai/A, respectively, The most sensitive dicot was cabbage, based on survival, 

with NOAEC and EC25 values of 10.21 and 9.93 lb ai/A, respectively. The reviewer cautioned that the 

results for the seedling emergence test should be interpreted 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) 

EC25 = 3.36 lb ai/A 

NOAEC = 23.15 lb 

ai/A for corn 

EC25 = 10.21 lb ai/A 

NOAEC = 9.93 lb ai/A 

for cabbage 

48859301 

Acceptable 

Terrestrial Vascular Plants: 

Vegetative Vigor TCMTB (30.6) 

EC25 = 0.79 lb ai/A 

NOAEC = 0.6 lb ai/A 

for corn 

EC25 = <0.25 lb ai/A 

NOAEC = 0.37 lb ai/A 

for soybean 

488859201 

Acceptable

 

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) Report: 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 under 0F0954; prepared by Woodard Research 

Corp., submitted by Buck- man Laboratories, Inc., Memphis, TN; CDL:091624-J) 
Page 62 of 65

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 Project 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 Toxicity 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 Supplement: Lab Project Number: 40089. 

Unpublished study prepared by ABC Laboratories, Inc. 56 p. 

42592901 Rhodes, J.; Stuerman, L. (1992) Early Life-stage 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. Project 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 the Effects of the Test Substance on Seedling 
Page 63 of 65

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 Analysis: 2-(thiocyanomethylthio) benzothioazole. 

Sample No. MB 618, Static Jar Test #2437, Terrestrial & Aquatic Biology Lab. 
Page 64 of 65

Appendix D Screening Level Down-theDrain Analysis 

The Down-the-Drain (DtD) module of E-FAST (Exposure 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-(thiocyanomethylthio) benzothiazole (TCMTB) 

and its degradates. The Down-the-Drain module uses daily per capita release of household 

wastewaters, stream dilution factors, and wastewater treatment plant removal efficiency to 

provide both high-end and median (average) time-averaged surface water concentrations of 

chemicals discharged by domestic wastewater treatment plants. The high-end scenario uses 

surface water concentrations downstream of domestic wastewater treatment plants based on the 

10th percentile stream dilution factor (SDF); the average scenario uses surface water 

concentrations based on the 50th percentile SDF. SDF is defined as the ratio of the stream flow 

downstream of a wastewater treatment plant to the wastewater treatment plant flow. Inputs used 

to run the DtD module included concentrations of concern (COCs) for aquatic organisms, 

percent removal during wastewater treatment, and hypothetical wastewater treatment plant 

influent volumes. The results of the DtD module are 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 LC50

values for freshwater organisms by 2. Endangered/listed COCs for freshwater fish and 

invertebrates were derived by dividing LC50 values by 20. EC50 values for plants were used to 

establish acute COCs for plants. NOAEC values 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 endangered 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 determine whether the model 

predicted exceedances of concentrations of concern. Then an average scenario was used to run 

the DtD model. 
Page 65 of 65

Appendix E Product Chemistry 

TCMTB product chemistry information is summarized 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 analytical 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/m3 

830.7370 Dissociation Constant Not applicable for non-aqueous products 

830.7550 Partition coefficient (n-octanol/water) 3.23 ± 3% at 20oC 

3.22 at 25oC 

830.7840 Solubility in water 45 mg/L ± 15% in water at 25oC 

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 (25oC)