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1, 2-Benzisothiazolin-3-one (BIT) Registration Review Team

Human Health & Environmental Effects

William Erickson

Srinivas Gowda

Najm Shamim

Siroos Mostaghimi

Jonathan Chen

Timothy Dole

Zoë Cavinder

Risk Management

Donna Kamarei

James Parker 

Office of General Counsel

Philip Ross
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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 

°C degrees Celsius

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 

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

μg microgram

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 
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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

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
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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

1.5 Regulatory History ......................................................................................................... 11

1.5.1 Tolerance Information ............................................................................................ 11

1.6 Incidents......................................................................................................................... 13

1.6.1 Human Health ......................................................................................................... 13

1.6.2 Ecological ............................................................................................................... 13

2 Anticipated Data Needs ........................................................................................................ 13

3 Human Health Risk Assessment........................................................................................... 17

3.1 Existing Toxicological Endpoints.................................................................................. 17

3.2 Dietary Exposure............................................................................................................ 19

3.2.1 Food ........................................................................................................................ 20

3.2.2 Drinking Water ....................................................................................................... 20

3.3 Occupational and Residential Exposures....................................................................... 21

3.3.1 Occupational Handler Exposure ............................................................................. 21

3.3.2 Residential Handler Exposures............................................................................... 22

3.3.3 Residential Post-Application Exposures................................................................. 22

3.4 Aggregate and Cumulative Exposure............................................................................. 23

3.4.1 Aggregate Exposures.............................................................................................. 23

3.4.2 Cumulative Exposures............................................................................................ 23

4 Environmental Risk Assessment........................................................................................... 23

4.1 Environmental Fate Assessment .................................................................................... 23

4.1.1 Leaching [Wood/Paint/Antifoulant Paint/Plastic/Textiles/e.g., treated article]...... 24

4.1.2 Water and Sediment................................................................................................ 24

4.1.3 Soil.......................................................................................................................... 24

4.1.4 Air ........................................................................................................................... 24

4.1.5 Water Quality.......................................................................................................... 24

4.2 Environmental Exposure Pathways................................................................................ 24

4.3 Ecological Effects Assessment....................................................................................... 26

4.3.1 Measures of Effect (Ecotoxicology Endpoints)...................................................... 26

4.4 Exposure Analysis Plan.................................................................................................. 27

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates ............................................ 27

4.4.2 Screening Level Down-the-Drain Analysis............................................................ 27

4.5 Effects Analysis Plan ..................................................................................................... 28

5 Endocrine Disruptor Screening Program (EDSP)................................................................. 28

6 Optional Label Changes........................................................................................................ 29

7 Guidance for Commenters.................................................................................................... 29

7.1 Preliminary Work Plan................................................................................................... 29

7.1.1 Trade Irritants.......................................................................................................... 29

7.1.2 Water Quality.......................................................................................................... 30
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7.1.3 Environmental Justice............................................................................................. 30

7.1.4 Additional Information ........................................................................................... 30

8 Next Steps............................................................................................................................. 31

9 References............................................................................................................................. 32

Appendix A Toxicology Profile............................................................................................... 33

Appendix B Environmental Fate ............................................................................................. 41

Appendix C Ecotoxicology Profile.......................................................................................... 44

Appendix D Screening Level Down-the-Drain Analysis ........................................................ 50

Appendix E Product Chemistry............................................................................................... 51

List of Tables

Table 1 – Summary of Anticipated Risk Assessments and Data Needs for Registration Review BIT 8

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

Table 3 – Chemical Identification of BIT.............................................................................................9

Table 4 – Physical-Chemical and Environmental Fate Properties for BIT...........................................9

Table 5 – Summary of BIT Registered Uses ......................................................................................11

Table 6 – Summary of BIT Food Contact Notifications.....................................................................13

Table 7 – Studies Anticipated as Needed for the Registration Review of BIT...................................15

Table 8 – Data Needs Required by the March 2008 Data Call-In for the BIT RED ..........................16

Table 9 – Existing Toxicological Endpoints.......................................................................................17

Table 10 – Occupational Handler Scenarios to be Assessed During Registration Review .................21

Table 11 – Residential Handler Scenarios to be Assessed During Registration Review.....................22

Table 12 – Residential Post-Application Scenarios to be Assessed During Registration Review .....22

Table 13 – Available Ecological Effects Endpoints ............................................................................27

Table 14 – Summary of Screening Level Down-the-Drain Analysis Results for Aquatic Organisms 29

List of Figures

Figure 1- Conceptual Model for Ecological Exposure and Effects of BIT to Aquatic and 

Terrestrial Organisms.................................................................................................................... 25
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1 Introduction

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

agency”) Preliminary Work Plan (PWP) for 1,2-Benzisothiazolin-3-one (BIT). The PWP 

document explains what EPA's Office of Pesticide Programs (OPP) knows about BIT, 

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 BIT’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 BIT and what types of new data or other

information would be helpful for the agency to receive as it moves toward a decision on BIT. 

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 and commit to a Final Work Plan (FWP) and 

anticipated schedule for the BIT case. 

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

in docket EPA-HQ-OPP-2014-0159. Tables 1 and 2 below summarize the issues relevant to this 

registration review case and the anticipated registration review schedule. 
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Table 1 – Summary of Anticipated Risk Assessments and Data Needs for Registration 

Review: BIT

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 and 8 for details)

Dietary (food) Yes 7/11/2005 Updated Product use information 

Dietary (drinking water) Yes N/A New Product use information

Occupational Handler Yes 9/01/2005 Updated Product use information, 90-day inhalation 

toxicology, immunotoxicity 

Residential Handler Yes 9/01/2005 Updated Product use information, 90-day inhalation 

toxicology, immunotoxicity

Residental Post Application 

- Incidental Oral and Dermal Yes 9/01/2005 Updated Indoor surface residues, product use information

Residental Post Application 

- Inhalation No 9/01/2005 Updated Product use information

Aggregate Yes 9/01/2005 Updated Product use information

Cumulative No N/A None None

Tolerance Review No N/A None None

Ecological Yes N/A New

Product use information, Aquatic plants, 

Leaching study, Ready biodegradability or one 

of three biodegradation in activated sludge 

simulation tests, Aerobic aquatic metabolism,

Activated sludge, respiration inhibition test

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 DCI, 

see Table 8.

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 2014-06 2014-06-25

Close Public Comment Period 2014-08

Phase 2: Case Development 

Issue Final Work Plan 2014-12

Issue Data Call-In (DCI) 2015-12

Receive Data to be Considered in Risk Assessment 2017-12

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2019-06

Close Public Comment Period 2019-07

Phase 3: Registration Review Decision and Implementation 

Open 60-Day Public Comment Period for Proposed Decision 2019-12

Close Public Comment Period 2020-02

Issue Final Decision 2020-06

Begin Post-Decision Follow-up 2020

Total (years) 6
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*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 the BIT case (case 3026) has been established at http://www.regulations.gov in 

docket number EPA-HQ-OPP-2014-0159.

1.3 Chemical Identification and Properties

Table 3 presents the active ingredient to be assessed in case 3026:1,2-Benzisothiazolin-3-one 

(PC Code 098901).

Table 3 – Chemical Identification of BIT

Chemical Name 1,2-Benzisothiazolin-3-one (BIT)

Chemical Classification Isothiazolone

PC Code 098901

CAS Number 2634-33-5

Molecular Formula C7H5NOS

Molecular Weight (grams/mole) 151.19

Molecular Structure

The BIT product chemistry information (MRID Nos. 43584001, 41927501, 43584001, 

42908201) relevant to risk assessment is summarized in Table 4, and the details of the 

environmental fate and product chemistry information are discussed in Appendix B and E, 

respectively.

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

Guideline No. Parameter 1,2-Benzisothiazolin-3-one (BIT)

Physical/Chemical Properties

830.7000 pH 4.25 - 1% slurry

830.7050 UV/Visible Absorption Stable with respect to sunlight

830.7200 Melting point (

oC) 159.5-160 oC 

830.7220 Boiling point (

oC) Not applicable

830.7300 Density 1.36±0.02 g/cm3

830.7370 Dissociation constant (pKa) Acid dissociation constant 9.12 x 10-8 moles/L (PAI)

pKa 7.04 at 25oC

830.7550 Octanol-water partition coefficient 

at 25 oC (Log Kow)

Log Kow 1.4 (PAI)

830.7840 Solubility in water (mg/L) 1118 ppm at 20 oC

1380 ppm at 24 oC

830.7860 Solubility in organic solvents n-Hexane: 100 ppm at 23 oC
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Guideline No. Parameter 1,2-Benzisothiazolin-3-one (BIT)

Ethyl acetate: 23000 ppm at 23 oC

Methanol: 67000 ppm at 24 oC

Acetonitrile: 13000 ppm at 23 oC

Acetone: 42000 ppm at 24 oC

Dichloromethane: 31000 ppm at 23 oC

Toluene: 5000 ppm at 24 oC

Heptane: 135 ppm at 20 oC

DMSO

830.7950 Vapor pressure (mmHg) 4.4 x 10-7 mm Hg at 20 oC (PAI)

9.8 x 10-7 mm Hg at 25 oC (PAI)

Environmental Fate Properties

Mobility

Organic Carbon Partitioning 

Coefficient (Koc)

From the Kd values, Koc were estimated: values range from 

254-728 mg/g

Persistence in Water (half-life)

Hydrolysis at 25 oC: pH 5, 7 &9

(days)

It is Hydrolytically stable at pHs 5, 7, and 9 under buffered 

conditions (MRID # 41199101, 44182101)

Aqueous photolysis at 25 oC 

(days)

The half-life of BIT at pH 5= 9 hours; pH 7 = 0.7 hours and at 

pH 9, the half-life is 0.7 hours. A number of photodegradates 

were identified: 1) ortho sulfbenzamide + 2-sulfobenzoic acid; 

2) 1,2-benzthiazolin-2-one; 3) hydroxy-1,2-benzthiazolin-3-

one and 4) sacchrin + 1,2-benzthiazolin-3-one-1,1-dioxide; 5) 

dihydroxy-1,2-benzthiazolin-e-one.

Two more degradates were observed (called degradate E, and 

M). these were not identified (MRID# 47329402)

Aerobic aquatic metabolism (days) No study was submitted

Anaerobic aquatic metabolism 

half-life (days) No study was submitted

Persistence in Soil (half-lifes)

Aerobic soil metabolism at 25 oC 

(days)

Half-life was measured between 0.4 to 3.6 days. It is not stable 

in aerobic soils and the degradates identified were: 1) ortho 

sulfbenzamide (same as in aqueous photolysis study; 2)BIT-soxide ;3) 1,2-benzthiazolin-3-one dioxide; 4) 2-

carbamylbenzenesulfonic acid. (MRID# 41199102, 41199103, 

93053102)

Anaerobic soil metabolism (days) No study was submitted

Persistence in WWTP (% 

removed)

Ready biodegradation No study was submitted

atm-m3/mol = atmosphere cubic meter per mole; oC = degrees Celsius; mg/L = milligrams per liter; mmHg = 

millimeters of mercury.

1.4 Use/Usage Description

1.4.1 Registrations

There are 68 EPA-registered products that contain BIT as an active ingredient (a.i.). Two of the 

registered products are technical, ten are registered as intermediate formulations, and 56 are 

registered as end use products. There are currently fourteen companies that have active products 

containing BIT. 
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1.4.2 Summary of Registered Uses

Table 5 presents a summary of all registered uses of BIT, all of which will be assessed in this 

registration review. BIT can be applied by the following application methods: paint brush, 

roller, airless sprayer (for paints containing BIT), wiping, mopping (for cleaning products 

containing BIT), open pour and meter pump injection (for incorporation as a material 

preservative and treatment of industrial processes and water systems).

Table 5 – Summary of BIT Registered Uses

Use Application Method Application Rate

Industrial Processes and Water Systems

Air washer water systems

Commercial/industrial water cooling systems

Industrial waste disposal systems

Pulp/paper mill water systems

Reverse osmosis water system

Secondary oil recovery injection water

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour, Meter Pump

1 to 4 ppm

1 to 4 ppm

1 to 4 ppm

35 to 950 ppm

3 ppm

1 to 308 ppm

Material Preservative

Adhesives, industrial

Automotive Evaporator Cores

Coatings, industrial

Emulsions, resin/latex/polymer

Leather processing liquors

Leather and Leather Products

Metalworking Fluids

Oil recovery drilling muds/packer fluids

Paints (in-can)

Paper/paper products

Plastic products

Rubber products

Household and Janitorial Cleaning Products

Laundry and Dishwashing Detergents

Textiles (carpets, canvas, drapes, mattress covers)

Open Pour, Meter Pump

Dip

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour

Open Pour

Open Pour

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour, Meter Pump

Open Pour, Meter Pump

25 to 2000 ppm

1770 ppm (in dip solution)

25 to 950 ppm

25 to 2900 ppm

60 to 950 ppm

475 to 4920 ppm

25 to 1760 ppm

1 to 9200 ppm

25 to 950 ppm

25 to 490 ppm

2000 ppm

162 to 500 ppm

25 to 1025 ppm

25 to 1025 ppm

25 to 2000 ppm

1.5 Regulatory History

The first product containing BIT as an active ingredient was registered in the United States on 

April 16, 1973. The agency completed a Reregistration Eligibility Decision (RED) for BIT in 

September of 2005 (9/29/2005). The post-RED Data Call-Ins (DCIs), PDCI-098901-27549 and 

GDCI-098901-27548 were issued in March of 2008.

1.5.1 Tolerance Information

For the active ingredient BIT, no pesticide tolerances or exemptions from tolerances have been 

established. BIT currently has one inert ingredient exemption from the requirement of a 

tolerance for residues as required under the Food Quality Protection Act (FQPA) section 408. 

The existing inert exemption is for use on growing crops under 40 CFR part 180.920. 
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BIT is listed as a food contact substance by FDA, eight food contact notifications (FCNs) have 

been granted (FFDCA Section 409). See Table 6 below. These FCNs are only effective for the 

manufacturer or supplier identified in the notification.

Table 6 – Summary of BIT Food Contact Notifications

FCN 

No. Manufacturer

Effective 

Date Intended Use Limitations/Specifications

1208

Prom Chem 

Limited

24-Oct-12

As an antimicrobial agent in can-end cements.

For use at levels not to exceed 0.015 percent by weight 

(150 parts per million, ppm) in can-end cements that will 

contact aqueous, acidic, low alcoholic (up to 8 percent v/v 

alcohol content) and fatty food under Conditions of Use A 

through H, and high alcoholic food (greater than 8 percent 

alcohol content) under Conditions of Use C through G, as 

described in Tables 1 and 2. The FCS is not intended to be 

used in packaging for infant formula.

1111

Thor GmbH of 

Speyer 

Germany

28-Dec-11

For use as a biocide in uncured liquid rubber latex 

solutions used to manufacture repeat-use rubber 

gloves.

The FCS may be used at a level not to exceed 0.05 weight 

percent of the latex on a solids basis. The finished glove 

may be used in contact with all food types.

1108

Lanxess 

Corporation

14-Dec-11

As a biocide in uncured liquid rubber latex used to 

manufacture repeat-use rubber gloves intended for 

use in contact with all types of food.

For use at levels not to exceed 0.05 percent by weight of the 

latex solids.

846

The Dow 

Chemical 

Company

10-Jan-09

As a biocide in uncured liquid rubber latex used to 

manufacture repeat-use rubber gloves intended for 

use in contact with all types of food.

For use at levels not to exceed 0.05 percent by weight of the 

latex solids.

835

Lanxess 

Corporation

26-Dec-08

As a biocide in uncured liquid rubber latex used to 

manufacture repeat-use rubber gloves intended for 

use in contact with all types of food.

For use at levels not to exceed 0.05 percent by weight of the 

latex solids.

504

Arch 

Chemicals, 

Inc.

2-Jul-05

The notifier intends to use the FCS as a wet state 

preservative (biocide) for styrene/acrylic or polymer 

lattices used in the manufacture of coatings 

(lacquer) which will be applied to the food contact 

side of single use articles made from aluminum 

foil for use with all food types under Conditions of 

Use B through H (see Table 2).

The FCS will not exceed 250 ppm in the wet emulsion. The 

wet coat weight will not exceed 1g/m2 on the food contact 

side of aluminum foil.

371

Arch 

Chemicals, 

Inc.

23-Dec-03

As a biocide in uncured liquid rubber latex used to 

manufacture repeat-use rubber gloves intended for 

use in contact with all types of food.

For use at levels not to exceed 0.05 percent by weight of the 

latex solids.

315

Avecia, Inc. 25-Apr-03

As a biocide in uncured liquid rubber latex used to 

manufacture repeat-use rubber gloves intended for 

use in poultry and meat processing plants.

For use at levels not to exceed 0.05 percent by weight of the 

latex solids.

Food Contact Notifications for 1,2-Benzisothiazolin-3-one (CAS Reg. No. 2634-33-5)
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1.6 Incidents

1.6.1 Human Health 

There are eight incidents listed in the OPP Incident Data System for the period 1/01/2005, to 

4/14/2014, when the data system was queried. All eight of these incidents were rated as minor

and skin irritation was the most commonly reported effect. One incident also resulted in swollen 

lips in addition to skin irritation. 

1.6.2 Ecological

No ecological incidents are in the Incident Data System (IDS, v. 1.8) as of April 1, 2014.

2 Anticipated Data Needs

Several studies were required from the assessment of BIT in the 2005 RED. In addition to the 

already-required RED DCI data, the following studies as listed in Table 7 are expected to be 

needed for the registration review of BIT. Table 8 outlines the data requirements required by the 

post-RED DCI issued on March 3, 2008. The agency anticipates reviewing any data received in 

response to the post-RED DCI as well as data requested for this registration review prior to 

conducting the registration review risk assessments for BIT.
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Table 7 – Studies Anticipated as Needed for the Registration Review of BIT

GLN Study Name Test Substance

Time Frame 

(Measured in months 

from DCI Receipt)

Risk Assessment(s) Data 

Will Support

Use Site(s) Triggering 

Anticipated Data Requirement

Applicable 

Exposure Scenario

Studies Anticipated to be Required through the Registration Review DCI

NonGuideline Leaching Study EP 12 Ecological Risk 

Assessments Treated wood Soil/water

NonGuideline Leaching Study EP 12 Ecological Risk 

Assessments Treated Textiles Aquatic medium

835.31101

835.32202

835.32403

835.32804

Ready 

biodegradability or 

one of three 

biodegradation in 

activated sludge 

simulation tests

TGAI/ DEGR 12

Ecological Risk 

Assessments - Fate and 

persistence in WWTPs 

Down the drain assessment

Paints, Material Preservatives, 

Drilling Muds and Flooding 

Fluids, Textiles

Aquatic 

environment

835.4400 Aerobic aquatic 

metabolism PAI 24 Ecological Risk Assessments

Metalworking Fluids, once 

through cooling towers Aquatic medium

850.33005 or 

OECD 209

Activated sludge, 

respiration inhibition 

test

TGAI/ DEGR 12

Ecological Risk 

Assessments -Fate and 

persistence in WWTPs 

Down the drain assessment

Paints, Material Preservatives, 

Drilling Muds and Flooding 

Fluids, Textiles

Toxicity to WWTP 

organisms

850.4400 Aquatic plant toxicity, 

Lemna sp.

TGAI 12 Ecological Risk 

Assessments All Aquatic environment

850.45006 Algal toxicity (3 spp.) TGAI 12 Ecological Risk 

Assessments All Aquatic environment

850.45506 Cyanobacteria TGAI 12 Ecological Risk 

Assessments All Aquatic environment

875.1700

875.2700

Product Use 

Information 

(Applicator/Postapplication)

TGAI or EP 12 All Risk Assessments All use sites All exposure 

scenarios

875.2300 Indoor Surface 

Residues TGAI 24 Residential Post Application Carpet fibers, Leather, Mattress Covers, Plastics, Floor cleaners See footnote 7

870.3465 90-day Inhalation 

Toxicology TGAI 24 Occupational and Residential All All potential exposures

870.7800 Immunotoxicity TGAI 24 Occupational and 

Residential All All potential exposures
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TGAI = Technical Grade Active Ingredient; TGAI/DEGR = Technical Grade of the Active Ingredient and Degradates; EP = End Use Product; PAI = Pure Active 

Ingredient.

1EPA has a published final guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0017. The required 

biodegradation study required is based on results of an Activated Sludge Respiration Inhibition test. 

2EPA has a published final guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0024. The required 

biodegradation study required is based on results of an Activated Sludge Respiration Inhibition test. 

3EPA has a published final guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0034. The required 

biodegradation study is based on results of an Activated Sludge Respiration Inhibition test. 

4EPA has a published final guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0036. The required 

biodegradation study required is based on results of an Activated Sludge Respiration Inhibition test. 

5 EPA published draft guidance under guideline 850.6800 and has since published final guidance for this study under guideline 850.3300: 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0021. OECD Test Guideline 209 can also be used as guidance for this study, 

available online at http://www.oecd-ilibrary.org/content/book/9789264070080-en. The results of the Activated Sludge Respiration Inhibition Test (ASRI) will 

determine which of these four biodegradation tests is/are required. If the ASRI test EC50 is less than or equal to 20 mg/L, then either the (i)Biodegradation in 

Activated Sludge Study or (ii) Simulation Test - Aerobic Sewage Treatment: A. Activated Sludge Units or (iii) the Porous Pot Test is required. If the ASRI test 

EC50 is greater than 20 mg/L, then the registrant must conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation 

Test - Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no 

further testing is required. If, however, the antimicrobial fails the Ready Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation 

Test - Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study is required. 

6 Results for studies conducted for (i) the freshwater green alga, Selenastrum capricornutum, (ii) the freshwater diatom, Navicula pelliculosa, (iii) the marine 

diatom, Skeletonema costatum, and (iv) the cyanobacteria species Anabaena flos-aquae, must be submitted to satisfy this requirement. Final 850 guidelines for the 

algal testing were posted in June 2012. The Public Draft OPPTS 850.5400 Algal Toxicity guideline was split into two separate guidelines and renumbered with the 

cyanobacteria species separated into OCSPP 850.4550 and the other three species under OCSPP 850.4500. 

7Exposure scenarios include dermal and/or incidental oral exposures to carpet fibers, clothing, leather, mattress covers, plastics, and floors preserved with BIT or 

cleaned with BIT preserved cleaning products.
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Table 8 –Data Needs Required by the March 2008 Data Call-In for the BIT RED

GLN Study Name Test 

Substance Status 

Studies Required through the Post-RED DCI

870.1300 Acute Inhalation 

toxicity TGAI Data have been submitted 

870.4200 Carcinogenicity TGAI Data have been waived

875.1200 Indoor Dermal 

Exposure

TGAI or 

surrogate Awaiting data submission

875.1400 Indoor Inhalation 

Exposure

TGAI or 

surrogate Awaiting data submission 

875.1600

Applicator 

Exposure 

Monitoring Data 

Reporting

TGAI or 

surrogate Awaiting data submission 

875.2800

Description of 

Human Activity TGAI or EP Awaiting data submission 

(Post Application)
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3 Human Health Risk Assessment

The agency anticipates the need to conduct a human health risk assessment for BIT. The agency

expects to require additional data for use in conducting the registration review.

3.1 Existing Toxicological Endpoints

On August 28, 2002 the Antimicrobials Division’s Toxicology Endpoint Selection Committee 

(ADTC) reviewed the available toxicology data for BIT with regard to the acute and chronic 

Reference Doses (RfDs) and the toxicological endpoint selection for use as appropriate in 

occupational/residential exposure risk assessments. The potential for increased susceptibility of 

infants and children from exposure to BIT was also evaluated as required by the FQPA of 1996. 

On February 8, 2005, the ADTC met again to consider additional data submitted by the registrant 

in response to the conclusions reached from the first meeting and as discussed in the September 

2002 ADTC memo. On May 17, 2012, the ADTC met again for several purposes: (1) to consider 

results of additional data submitted since the issuance of the RED for BIT in 2005 and its impact 

on the previously selected endpoints; (2) to re-evaluate the conclusions reached previously on 

neurotoxicity; (3) to re-evaluate the impact of the lack of a developmental toxicity study in the 

rabbit for BIT; and (4) to update the mutagenicity and carcinogenicity sections of the ADTC 

memo. The toxicological end-points selected are summarized in Table 9. 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 MOE, UF, Special FQPA SF, 

for Risk Assessment

Study and Toxicological 

Effects

Dietary Risk Assessments

Acute Dietary

General population, 

including infants and 

children

NOAEL= 5 

mg/kg/day

UF = 100 (10x inter-species 

extrapolation, 10x intra-species 

variation)

FQPA SF= 1

DB UF = 1

Acute RfD =0.05 mg/kg/day

Co-Critical studies:

Subchronic toxicity (dog) 

NOAEL = 5 mg/kg/day 

based on increased 

incidence of emesis and 

clinical chemistry 

alterations at 20 

mg/kg/day.

Subchronic toxicity (rats) 

NOAEL = 8.42 

mg/kg/day based on 

macroscopic and 

microscopic lesions in the 

non-glandular and 
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Exposure

Scenario

Dose Used in 

Risk Assessment

(mg/kg/day)

Target MOE, UF, Special FQPA SF, 

for Risk Assessment

Study and Toxicological 

Effects

glandular regions of the 

stomach.

Chronic Dietary 

All populations

NOAEL =5 

mg/kg/day

UF = 300 (10x inter-species 

extrapolation, 10x intra-species 

variation)

FQPA SF = 1

DB UF = 3 (for extrapolation from 

subchronic to chronic)

Chronic RfD = 0.017 mg/kg/day

Co-critical studies:

Subchronic toxicity (dog) 

NOAEL = 5 mg/kg/day 

based on increased 

incidence of emesis and 

clinical chemistry 

alterations at 20 

mg/kg/day.

Subchronic toxicity (rats) 

NOAEL = 8.42 

mg/kg/day based on 

macroscopic and 

microscopic lesions in the 

non-glandular and 

glandular regions of the 

stomach.

Non-Dietary Risk Assessments

Incidental Oral

(short and 

intermediate term)

NOAEL =5 

mg/kg/day

MOE = 100 (10x interspecies 

extrapolation, 10x intraspecies 

variation)

Co-critical Studies:

Subchronic toxicity (dog) 

NOAEL = 5 mg/kg/day 

based on increased 

incidence of emesis and 

clinical chemistry 

alterations at 20 

mg/kg/day.

Subchronic toxicity (rats) 

NOAEL = 8.42 

mg/kg/day based on 

macroscopic and 

microscopic lesions in the 

non-glandular and 

glandular regions of the 

stomach.
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Exposure

Scenario

Dose Used in 

Risk Assessment

(mg/kg/day)

Target MOE, UF, Special FQPA SF, 

for Risk Assessment

Study and Toxicological 

Effects

Dermal

All time periods

(occupational and 

residential)

LOAEL = 100 

mg/kg/day

MOE =1000 (10x interspecies 

extrapolation, 10x intraspecies 

variation, 10x for lack of NOAEL)

Subchronic dermal 

toxicity (rat) 

LOAEL = 100 

mg/kg/day, based on 

macroscopic and 

microscopic changes in 

the stomach. 

NOAEL not established. 

Inhalation

All time periods

(occupational and 

residential)

NOAEL = 5 

mg/kg/day

MOE = 100 (10x interspecies 

extrapolation, 10x intraspecies 

variation,).

An additional 10x factor for route 

extrapolation is used based on the use 

of an oral endpoint (route-to-route 

extrapolation). 

Co-critical studies:

Subchronic toxicity (dog) 

NOAEL = 5 mg/kg/day 

based on increased 

incidence of emesis and 

clinical chemistry 

alterations at 20 

mg/kg/day.

Subchronic toxicity (rats) 

NOAEL = 8.42 

mg/kg/day based on 

macroscopic and 

microscopic lesions in the 

non-glandular and 

glandular regions of the 

stomach.

Carcinogenicity N/A Cancer study waived because risk assessment endpoints are 

protective of irritation effects. 

3.2 Dietary Exposure

The agency plans to update the dietary exposure (food and drinking water) assessments for BIT 

in order to support registration review. The food assessment must be updated to include uses 

that may result in exposure to food but were not previously assessed in support of the 2005 RED. 

The specific uses that need to be assessed are household and janitorial cleaning products and 

dishwashing detergents. Additionally, a drinking water assessment was not conducted as part of 

the 2005 RED, and will be included in the updated dietary exposure assessment.

Antimicrobial uses of BIT that may result in dietary exposure (food) include use in home and 

janitorial cleaning products, dishwashing detergent, as a slimicide in paper manufacturing, and as 

a preservative in coatings, adhesives, emulsions, paper/paper products, and plastics. All of these 

uses are considered indirect food uses because, although BIT is not intended to be applied 

directly to food, the use pattern may result in food contact. With respect to drinking water 

exposure, several approved uses including use as a material preservative and in industrial water 
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systems may result in BIT being discharged into waste water or leached from preserved materials 

and subsequently running off into surface water.

3.2.1 Food

BIT was previously evaluated as part of the U.S. EPA’s 2005 RED. All of the uses that may 

result in dietary exposure were evaluated except household and janitorial cleaning products and 

dishwashing detergents. As part of the 2005 RED, the agency conducted a dietary exposure and 

risk assessment for the use of BIT as a pulp and paper mill slimicide, and as a preservative in 

paper coatings and adhesives. For both the acute and chronic dietary exposure, the risk is highest 

for children (21.8% of the acute and chronic PAD). For an adult, the acute and chronic dietary 

exposure is 9.4% of the acute and chronic PAD. All dietary exposures calculated are below the 

agency’s level of concern (100% of aPAD or cPAD) for non-cancer risk.

Since the 2005 RED, new uses as cleaning products and dishwashing detergents were granted

and FCNs became effective for wet state preservatives, biocides in uncured liquid rubber latex 

used to manufacture repeat-use rubber gloves, and for can-end cements. Since these can 

contribute to dietary (food) exposure, the agency will need to conduct both acute and chronic 

dietary exposure assessments for all population subgroups to support registration review. In an 

effort to determine if additional residue data will be required to conduct these assessments, a 

screening level analysis was conducted for both the dish detergent use and the household 

cleaning products use. Both of these screens used FDA methodology (FDA, 1993) where 

appropriate as well as relied on high-end assumptions to be protective of human health. The 

toxicological points of departure used for the analyses were from a subchronic toxicity study 

with a NOAEL of 5 mg/kg/day. For the acute RfD a 100x uncertainty factor was applied in 

order to account for intra- and interspecies variation. For the chronic RfD a 300x uncertainty 

factor was applied in order to account for intra- and interspecies variation and for extrapolation 

from subchronic to chronic.

The previous risk assessment conducted in support of the RED as well as the screening level 

assessment conducted for dishwashing detergent and household cleaning product uses indicate 

that no further residue data will be required when the current toxicological information available 

is used to conduct the assessment. The exposure contributions from these two scenarios will be 

considered in the aggregate assessments conducted during registration review. It is important to 

note that if the toxicological point of departure for either the acute or chronic scenario changes 

based on data received during the registration review process, additional residue chemistry data 

may be required.

3.2.2 Drinking Water

A drinking water assessment has not been conducted for BIT in the past. However, for several 

approved uses (including some plastics, household cleaners, textile, paints, adhesives, oil 

recovery drilling fluids and water cooling systems) the agency cannot rule out the potential for 

BIT to enter surface water and to subsequently be present in drinking water. Since drinking 

water risk is a function of many unknown factors including (1) the residues of concern in 

drinking water, (2) the magnitude of these potential residues of concern, (3) the persistence of 

BIT in water, and (4) if residues of BIT are likely to pass through a wastewater treatment plant 
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(WWTP), 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 BIT 

will pass through a WWTP. Upon receipt and review, these data and/or other sources of 

information will be used during the risk assessment stage of this Registration Review to 

determine the potential for discharged or leached residues of BIT to result in human dietary 

exposure via drinking water, which may trigger a drinking water assessment.

3.3 Occupational and Residential Exposures

The agency anticipates the need to revise the Occupational Residential Exposure (ORE) 

assessment (EPA, 2005) that was written for the BIT 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 or are anticipated to 

be required for registration review of BIT. 

3.3.1 Occupational Handler Exposure

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

the 2005 RED. The exposures assessed include liquid pouring for industrial water systems 

treatment, oil and gas drilling fluids and material preservation and use of preserved materials

such as cleaning products and paint. Both dermal and inhalation exposures were assessed and 

were considered to be of short to intermediate term in duration. The dermal MOEs ranged from 

90 (airless sprayer application) to 450,000 and were generally not of concern because they 

exceeded the target MOE of 100. The inhalation MOEs ranged from 1,700 to 7,000,000 and 

were not of concern because they exceeded the target MOE of 1000. Based on these MOEs, the 

RED did not specify any risk mitigation.

The exposure to machinists using metal working fluids treated with BIT 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 Assessed 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 

Brush/roller and airless sprayer application of BIT 

preserved paints Dermal, Inhalation Short and Intermediate Term 

Machinist exposure to BIT preserved MWF Dermal, Inhalation Long Term 
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Scenario Exposure Route(s) Duration

Mop wipe and trigger sprayer application of BIT 

preserved cleaning products. Dermal, Inhalation Short and Intermediate Term 

3.3.2 Residential Handler Exposures

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

2005 RED. Residential handler dermal and inhalation exposures to BIT were assessed in the 

RED for moping and wiping using BIT preserved cleaning products and for brush/roller and 

airless sprayer application of BIT preserved paints. The dermal MOEs ranged from 140 (airless 

sprayer application) to 48,000 and were not of concern because they exceeded the target MOE of 

100. The inhalation MOEs ranged from 5,600 to 590,000 and were not of concern because they 

exceeded the target MOE of 1000. Based on these MOEs, the RED did not specify any risk 

mitigation.

The residential handler scenarios will need to be assessed for registration review are listed in 

Table 11. 

Table 11 – Residential Handler Scenarios to be Assessed During Registration Review

Scenario Exposure Route(s) Duration

Mop, wipe and trigger spray application of BIT preserved 

cleaning products Dermal, Inhalation Short and Intermediate Term 

Brush/Roller and airless sprayer application of BIT 

preserved paints Dermal, Inhalation Short and Intermediate Term 

3.3.3 Residential Post-Application Exposures

EPA anticipates the need to revise the residential post-application assessment conducted in 

support of the 2005 RED. Residential post-application dermal and incidental oral exposures to 

residues arising from contact with vinyl flooring cleaned with BIT preserved floor cleaning 

products and clothing laundered with BIT preserved laundry detergent were assessed. The 

MOEs for dermal exposure ranged from 7,200 to 11,000 and they were not of concern because 

the exceeded the target MOE of 100. The MOEs for incidental oral exposures ranged from 1,700 

to 65,000 and were not of concern because they exceeded the target MOE of 300. 

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

of BIT are listed in Table 12.

Table 12 – Residential Post-Application Scenarios to be Assessed During Registration 

Review

Scenario Exposure Route(s) Duration

Carpet fibers - child Dermal and Incidental Oral Short and Intermediate Term 

Clothing – child and adult Dermal and Incidental Oral Short and Intermediate Term 

Leather – child and adult Dermal and Incidental Oral Short and Intermediate Term 

Mattress Covers – child and adult Dermal Short and Intermediate Term 
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Plastics – child Incidental Oral Short and Intermediate Term 

Flooring cleaned with BIT preserved cleaners – child Dermal and Incidental Oral Short and Intermediate Term 

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 2005 

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) 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 BIT and any other substances and BIT 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 BIT 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

No ecological risk assessment was conducted for the RED (EPA 2005). In 2013, the agency

completed an environmental risk assessment for the new use of BIT for industrial use in the 

manufacture of roofing membranes. The agency concluded that this new use of BIT did not 

exceed any acute or chronic level of concerns (LOCs) for listed or nonlisted aquatic organisms

that might be exposed to BIT leached from roofing membranes and transported to the aquatic 

environment. Other uses have not been assessed for ecological risks.

The ecological risk assessment planned during registration review will allow the agency to 

determine potential risks to aquatic organisms exposed to BIT and its transformation products 

that may be transported to the aquatic environment. The risk assessment will allow the agency to 

determine whether each use of BIT 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

BIT is water soluble and is not likely to volatilize from water surfaces. In aqueous photolysis 

process, the half-life of BIT is 0.7 hours at pH 7 and 9. The six identified photodegradates are 
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not stable, and in the 30 day study the concentrations decreased to low percentages in the 

aqueous medium. Under aerobic conditions BIT degrades quickly with a maximum half-life of 

3.6 days. Due to water solubility and moderate mobility in soils, and fast degradation on soil 

surfaces, the degradates are likely to reach the sediments. Any potential water contamination is 

likely due to degradates and not parent BIT. The agency anticipates requiring a number of fate 

studies based on the various use scenarios including aerobic and anaerobic aquatic metabolism 

and leaching from wood and textiles studies. The agency will conduct a full risk assessment.

4.1.1 Leaching [Wood/Paint/Antifoulant Paint/Plastic/Textiles/e.g., treated 

article]

No leaching data are available. Leaching data are anticipated to be needed to assess potential 

exposures from wood preservative and textile uses. 

4.1.2 Water and Sediment

BIT is water soluble and partitions into soils/sediments. No aerobic or anaerobic aquatic studies 

were submitted for assessment; however, in the aqueous system it photolyzes quickly at all three 

pHs, and it forms a number of photodegradates as indicated above.

4.1.3 Soil

BIT degrades quickly in aerobic soils, with a half-life of 3.6 days (MRID# 4119102, 41199103).

4.1.4 Air

BIT has a low vapor pressure (4.4 x 10-7 mmHG, see Table 4) and it is not likely to volatilize in 

air.

4.1.5 Water Quality

BIT 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, 2014)

1

. In addition, no Total 

Maximum Daily Loads (TMDL) have been developed for BIT, based on information provided at 

the agency’s National Pesticide TMDL web site (searched April, 2014)

2

. More information on 

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

4.2 Environmental Exposure Pathways

Aquatic organisms potentially at risk from exposure to BIT include those inhabiting water bodies 

adjacent to or downstream from sources of down-the-drain discharges (e. g., waste water 

treatment plants), cooling tower direct discharge, or from environmental transport of BIT leached 

from application of paints and coatings to exterior surfaces. 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. 

 

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

2http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES
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Aquatic organisms likely to be acutely exposed include fish, invertebrates, aquatic stages of 

amphibians, and aquatic and semi-aquatic plants. Chronic exposure is possible due to 

continuous or repeated exposures from residential and industrial down-the-drain discharges.

Exoposure from the use in cooling towers is represented in the conceptual diagram below. 

Figure 1- Conceptual Model for Ecological Exposure and Effects of BIT to Aquatic and 

Terrestrial Organisms

Stressor

Source

Receptors 

and Exposure 

Routes

Attribute

Change(s)

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae

Reduction in prey

Modification of PCEs related 

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related to 

habitat

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Ingestion Ingestion

Uptake/gills 

or integument

Aquatic Plants

Non-vascular

Vascular

Uptake or sorption/cell, roots, 

leaves, 

Piscivorous*

Invertebrates

Vertebrates

Phytoplanktivore/ 

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal (e.g., amphibians, mollusks, crustaceans, etc.)

Ingestion

Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway 

contributing to risk

Low likelihood of 

contributing to risk

Cooling Tower (Once Through and/or Recirculating)

WWTP 

microorganisms

Uptake or 

sorption

Population

Respiration 

inhibition

Direct 

Discharge

Surface Water

Sediment

Volatilization

Terrestrial birds 

and mammals

Inhalation 

exposure 

pathway see 

Figure (B)

(A)
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4.3 Ecological Effects Assessment

4.3.1 Measures of Effect (Ecotoxicology Endpoints)

Ecological effects data are used as measures of direct and indirect effects to aquatic and 

terrestrial organisms. Acute and chronic toxicity data from registrant-submitted studies 

conducted in accordance with the 850 OCSPP Harmonized Test Guidelines are used to evaluate 

the potential direct and indirect effects to plants and animals. Relevant data from the open 

literature also may be used if available.

4.3.1.1 Submitted data 

All data requirements and available ecotoxicity endpoints from studies submitted by registrants 

are tabulated in Appendix C. OPP uses the most sensitive of these endpoints for assessing risk to 

each terrestrial and aquatic receptor group. The available endpoints selected for the risk 

assessment for BIT are provided in Table 13. Data gaps exist for aquatic plants. 

Table 13- Available Ecological Effects Endpoints 

Receptor 

Group

Test 

Material

Risk 

Scenario Toxicity Endpoint Reference

Freshwater fish TGAI

Acute LC50 = 0.54 mg ai/L 443649-13

Chronic NOAEC = 0.28 mg ai/L 477598-15

Freshwater 

invertebrates TGAI

Acute EC50 = 1.5 mg ai/L 455346-01

Chronic NOAEC = 0.91 mg ai/L 477598-14

Estuarine/marine fish TGAI

Acute LC50 = 12.2 mg ai/L 429450-01

Chronic Not required --

Estuarine/marine 

invertebrates TGAI

Acute EC50 = 0.047 mg ai/L 429524-01

Chronic Not required --

Aquatic plants -

Lemna

TGAI EC50

NOAEC Data gap --

Aquatic plants -

algae

TGAI EC50

NOAEC Data gap --

Cyanobacteria TGAI EC50

NOAEC Data gap --

Birds TGAI Acute oral LD50 = 453 mg ai/kg bw 409913-01
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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 environment. Resulting exposure estimates will be compared to the 

toxicity endpoints to determine if levels of concern are exceeded for each receptor group. 

4.4.2 Screening Level Down-the-Drain Analysis

The Down-the-Drain (DtD) module of E-FAST (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 BIT to be exposed to BIT 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 E. A conservative assumption of no removal during wastewater 

treatment was used in DtD model runs.

The DtD analysis for BIT is intended to serve two purposes: (1) to demonstrate the maximum 

WWTP influent volume of BIT that would trigger potential concerns for aquatic organisms 

exposed to BIT 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 BIT 

enters domestic wastewater treatment plants. A key purpose of the DtD analysis for BIT is to 

determine the lowest maximum annual WWTP influent volumes of BIT that would trigger 

potential concerns for aquatic organisms downstream of domestic WWTPs.

Table 14 presents results of a screening-level DtD analysis for BIT which was based on 

laboratory toxicity data for freshwater organisms. Based on these aquatic toxicity data and the 

total annual production volume of BIT, the DtD model predicted exceedances of concentrations 

of concern for acute and endangered aquatic organisms. In addition, a DtD analysis predicted 

that over 150000 kg/yr of BIT 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 14 – Summary of Screening Level Down-the-Drain Analysis Results for Aquatic 

Organisms

WWTP Influent 

Volume

Freshwater Fish, Acute 

(COC = 270 ug ai/L)

Freshwater Invertebrates, acute

(COC = 75 ug ai/L)

Endangered species - aquatic 

plants (COC = 400 ug ai/L)

High-End Scenario

2800000 

kilograms/year Exceeded 4 days per year Exceeded 40 days per year Exceeded 2 days per year

150000 

kilograms/year No exceedances Exceeded < a day No exceedances
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Average Scenario

2800000

kilograms/year Exceeded < 1 day Exceeded 4 day Exceeded < 1 day

150000 

kilograms/year No exceedance Exceeded < 1 day No exceedance

This screening level analysis assumes that BIT and salts are released to domestic wastewater 

treatment plants. Based on registered uses of BIT and salts 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 BIT that could be expected to enter 

domestic wastewater treatment plants. There is also uncertainty about the potential for exposure 

to aquatic organisms from BIT entering industrial wastewater treatment plants as a result of 

industrial uses of BIT. The agency does not have high quality data on the toxicity of BIT to 

activated sludge microorganisms in wastewater treatment plants and does not have high quality 

data on biodegradation of BIT during wastewater treatment. Consequently, the agency

anticipates requiring data addressing toxicity to activated sludge microorganisms and 

biodegradation of BIT during wastewater treatment.

4.5 Effects Analysis Plan

The ECOTOX database will be searched during the risk assessment phase and the data will be 

reviewed following the agency’s policy for reviewing public literature for use in assessing risks 

from pesticides (http://www.epa.gov/pesticides/science/literature-studies.html). Those 

ecotoxicity values found in the public literature to be more sensitive than those currently in the 

data and 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 its 2005 reregistration decision, for BIT, 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), BIT is subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP). 
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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, 20133and includes some pesticides 

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

construed as a list of known or likely endocrine disruptors.

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

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

website.4

6 Optional Label Changes

The agency invites comments 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, registrants may consider amending product labeling.

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 BIT 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 

 

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

chemicals.

4 http://www.epa.gov/endo/
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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 Process5in 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 

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 BIT 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 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

 

5 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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8. Monitoring data 

8 Next Steps

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

any comments received in a timely manner, and then issue a Final Work Plan for the BIT case.
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9 References 

U.S. Environmental Protection Agency (EPA). 2002. ECOTOX User Guide: ECOTOXicology 

Database System. Version 3.0. Available: http://www.epa.gov/ecotox/

U.S. Environmental Protection Agency. High Production Volume Information System (HPVIS). 

http://www.epa.gov/hpvis/
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Appendix A Toxicology Profile

Acute Toxicity for Product Labeling 

As summarized in Table 16, acute toxicity data show that 1,2-benzisothiazolin-3-one is 

moderately toxic by the oral and dermal routes (Toxicity Category III for both studies); however, 

this chemical is a severe eye irritant. Irritation to the skin from acute data show only mild skin 

irritation. This response could be related to the ability of this chemical to cause a moderate skin 

sensitization response.

Table 16 – Acute Toxicity Studies for BIT

Guideline

Number

Study Type MRID

Numbers

Results Toxicity Category

870.1100 Acute Oral 41022101; 

42858101

LD50 = 670 mg/kg (M); 

784 mg/kg (F) III

870.1200 Acute Dermal 41022102; 

42858102 LD50 > 2000 mg/kg III

870.1300 Acute Inhalation --- --- See footnotesa,b

870.2400 Primary Eye 

Irritation 42905102 severe eye irritant I

870.2500 Primary Skin 

Irritation 42905101 slight irritant IV

870.2600 Dermal 

Sensitization

41750001; 

42858103

moderate dermal 

sensitizer N/A

a On the basis of the recently published waiver guidance for conduct of acute toxicity studies 

(http://www.epa.gov/pesticides/science/acute-data-waiver-guidance.pdf), a waiver can be granted for the acute 

inhalation toxicity test for the technical test material. In MRID 42905103, the registrant showed that the majority of 

particles generated from Proxel Press paste are greater than 15 um aerodynamic diameter, and are thus larger than 

the 1-4 um diameter targeted for acute inhalation toxicity tests with solids. 

bData waivers were not granted for any of the aqueous-based formulations. Thus, aqueous solutions of 1, 2-

benzisothiazolin-3-one will require acute inhalation toxicity data.

Subchronic Toxicity 

There are two subchronic dog studies. In a subchronic oral toxicity study in dogs (MRID 

42205701) BIT (94.6% a.i., w/w) was administered to 4 beagle dogs/sex/dose by capsule at dose 

levels of 0, 5, 20, or 50 mg/kg/day for 92 days. No animals died during the study. The only 

treatment-related clinical observation was an increased incidence of emesis in both sexes of 

dogs, primarily at the higher dose levels. Treatment with resulted in no differences in body 

weight or total body weight gain compared to controls. Hematological alterations were sporadic 

and not considered to be dose-related. Clinical chemistry parameters that were altered 
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significantly from controls (p# 0.05 or 0.01) at the high dose in both sexes for one or more weeks 

include plasma albumin (9-11% decrease), total protein (7-13% decrease), alanine transaminase 

(26-30% decrease), and triglycerides (30-49% increase). These results were accompanied by 

increased absolute liver weight in high-dose dogs of both sexes (17%) and mid-dose females 

(12%), and are consistent with an adverse effect on liver function. There were no treatment 

related effects on gross or microscopic pathology, food consumption, or ophthamology. The 

LOAEL is 20 mg/kg/day for both male and female dogs, based on the incidence of emesis 

and clinical chemistry alterations at this dose. The NOAEL is 5 mg/kg/day. 

In the second subchronic dog oral toxicity study (MRID 47759802), BIT (89.8% a.i; Lot #: 

2005-051) was administered to 4 beagle dogs/sex/dose in diet at dose levels of 0, 300, 1000, or 

3000 ppm (equivalent to 0, 11, 37, and 106 mg a.i./kg bw/day for males; and 0, 11, 38, 89 mg 

a.i./kg bw/day for females). There was no mortality or signs of clinical toxicity observed in either 

male or female dogs treated at any dose level. There were no toxicologically significant effects 

on hematological, clinical chemistry, organ weights, gross or histopathology by oral 

administration of 1,2-benzisothiazolin-3-one. In the 3000-ppm dose group, mean cumulative 

body weight/mean cumulative body weight gain was significantly lower in male dogs during 

weeks 0-4 of the study and in females throughout the study period. During week 13, mean body 

weights of the 3000-ppm male and female dogs were 6.6% and 18.7% lower than the 

corresponding control animals. Decreases in mean food consumption correlated with the 

decreased body weight. Although there were several changes in organ weights in high-dose 

females, these were all secondary to the reduced body weight. Based on the effects on food 

consumption and body weight, the LOAEL is 3000 ppm (106 mg a.i/kg bw/day – male; 89 mg 

a.i./kg/day – female). The NOAEL is 1000 ppm (37 mg a.i./kg bw/day – male; 38 mg a.i./kg 

bw/day – female). This 90-day oral toxicity study in the dog is Acceptable Guideline and 

satisfies the guideline requirement for a 90-day oral toxicity study (OPPTS 870.3150; OECD 

409) in non-rodent species. 

There are two subchronic rat oral studies. In a subchronic oral toxicity study in rats (MRID 

46346201), BIT (84.2% a.i., Batch # 22001 014), suspended in carboxymethyl- cellulose, was 

administered to 10 HsdCpb: WU conventionally bred (inhouse random bred) Wistar 

rats/sex/dose by oral gavage at dose levels of 0, 10, 30, and 75 mg/kg bw/day (0, 8.42, 25.26, and 

63.15 mg a.i./kg/day, respectively). In addition, 10 rats/sex/dose were administered 0 and 75 

mg/kg/day (63.15 mg a.i./kg/day) for 90 days, followed by a 28-day recovery period. The 

LOAEL is identified as 30 mg/kg/day (25.26 mg a.i./kg/day), based on the incidence of 

macroscopic and microscopic lesions in both sexes. The NOAEL is 10 mg/kg/day (8.42 mg 

a.i./kg/day). This subchronic toxicity study in the rat is acceptable-guideline and satisfies the 

guideline requirement for a 90-day oral toxicity study (OPPTS 870.3100; OECD 408) in rats. 

In the second 90-day rat oral toxicity study (MRID 47759801) 1, 2-benzisothiazolin-3-one 

(89.8% a.i., batch/lot #2005-051) was administered to 10 Sprague-Dawley (Crl:CD) 

rats/sex/dose by gavage of 5 mL/kg at initial dose levels of 0, 10, 25, or 65 mg/kg/day once a day 

for 91 or 92 concurrent days. The initial dose of 65 mg/kg/day was lowered to 50 mg/kg/day on 

day 15 due to mortality and negative health effects.

Mortality was observed in three males and four females in 65/50 mg/kg/day group. Clinical 

signs of cardiopulmonary distress and/or behavioral/CNS related toxicity were observed at 65/50 
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mg/kg/day during a week prior to death. Upon examination extensive gastric lesions, including 

hyperplasia and hyperkeratosis of the mucosa of the forestomach, erosions, ulcers, mucosal 

hemorrhage and/or submucosal inflammation in the glandular and/or nonglandular areas, were 

found and considered to be the cause of death. Additionally, one male in the 10 mg/kg/day 

group died on day 47. This rat showed mild necrosis of the laryngeal mucosa and disseminated 

necrosis of the tracheal mucosa, presumably due to aspiration of the treatment substance, which 

is thought to have been a factor in the death of this animal. 

Other observations included a decrease in mean body weight gain in the 65 mg/kg/day group 

during weeks 1 and 2, as compared to controls, although no effects on food consumption were 

noted. No neurotoxic effects (week 11) or ophthalmic toxicity (week 12) were found in any of 

the treatment groups. Hematological evaluations indicated lowered albumin and globulin levels 

resulting in a significantly lower total protein in the 65/50 mg/kg/day males and females, which 

was consistent with the lesions found in the stomach including ulceration and erosions, 

submucosal inflammation and areas of superficial hemorrhage or hyperplasia of the glandular 

mucosa in this treatment group. 

Treatment-related dose-dependent microscopic findings in the stomach, most commonly 

thickening of the nongladular (forestomach) mucosa resulted from hyperplasia and 

hyperkeratosis of the squamous mucosa, ranging from minimal in the low-dose group to marked 

diffuse in the high-dose animals, were observed in all treatment levels in both male and female 

rats. Additional changes, including superficial mucosal erosions or ulcers and submucosal 

inflammation in the nonglandular area of the stomach, were found only in the mid and high dose 

groups.

The LOAEL is 10 mg/kg/day, based on microscopic findings in the stomach. The NOAEL 

could not be determined. This 90-day oral toxicity study in the rat is ACCEPTABLE 

GUIDELINE and satisfies the guideline requirement for a 90-day oral toxicity study (OPPTS 

870.3100; OECD 408) in rats.

There is one acceptable rat dermal 90-day study. In the study (MRID 45184601), BIT (98.71% 

a.i., lot #579) was applied to the shaved dorsal skin of 10 Wistar albino rats/sex/dose at dose 

levels of 0, 100, 300, or 1000 mg/kg-d, 6 hours/day for 5 days/week during a 90-day period. The 

application site was occluded. 

No mortality or clinical signs of systemic toxicity were observed during this study. No effects 

were observed on body weight or food consumption. Treatment-related skin abnormalities and 

microscopic changes to the stomach mucosa were observed in rats from all treatment groups. 

The most common microscopic changes were thickening of the epidermis and nonglandular 

mucosa of the stomach due to hyperplasia and hyperkeratosis. No other treatment-related gross 

or microscopic changes in pathology were found. Hematological evaluations indicated a 

significant increase in the white blood cell count of females treated with 1000 mg/kg-d when 

compared to controls. Slight changes in clinical chemistry were observed with a significant 

increase in triglycerides for 300-mg/kg-d females and significant decreases in albumin and total 

protein levels in 1000-mg/kg-d females. The mean relative liver weight of males treated with 

1000 mg/kg-d was significantly higher than controls. The systemic LOAEL is 100 mg/kg-d, 

based on macroscopic and microscopic changes to the stomach mucosa. A NOAEL for the 
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systemic effects cannot be determined. The LOAEL for local effects is 100 mg/kg-d, based 

on macroscopic and microscopic changes in the treated skin. A NOAEL for local effects 

cannot be determined. This 90-day dermal toxicity study in the rat is ACCEPTABLE / 

GUIDELINE and satisfies the guideline requirement for a 90-day dermal toxicity study (OPPTS 

870.3250) in rodents.

There is no subchronic inhalation study. A 90-day repeat-dose inhalation toxicity study is

identified as a data gap to properly assess inhalation risks from all uses of this active ingredient, 

as extrapolation from an oral toxicity study may underestimate inhalation risk.

Developmental Toxicity 

There were two developmental toxicity studies conducted in rats with 1,2-benzisothizolin-3-one. 

One study (MRID 43663008) used 100% a.i. in carboxymethylcellulose by gavage, while the 

other study (MRID 40961201 and 42858104) used a paste of 73.4% purity administered by 

gavage in 0.5% hydroxy methyl propyl cellulose that was diluted in 0.1% polysorbate 80. 

Although the dose levels in these two studies were similar (0, 10, 30, and 90 mg/kg/day for the 

first study, and 0, 10, 40, and 100 mg/kg/day for the second study [doses corrected for % a.i.]), 

the maternal toxicity LOAELs were not similar and similar effects were not observed at these 

doses. In MRID 43663008, the maternal toxicity LOAEL was 30 mg/kg/day based on mortality 

and clinical signs, while in MRID 40961201, the maternal toxicity LOAEL was 100 mg/kg/day 

based on decreased body weight gain and food consumption. Neither of these two studies 

indicated any evidence of sensitivity of offspring to the toxicity of 1,2-benzisothizolin-3-one in 

rats.

Reproductive Toxicity

There are two reproduction and fertility effects studies are currently available for BIT. The 

agency has reviewed these studies and their respective executive summaries are presented below. 

In a 2-generation reproduction study (MRID 46097101), BIT (~ 93% pure) was administered to 

24 rats (Crl:WI[Glx/BRL/Han]BR)/sex/dose via diet at concentrations of 0, 250, 500, or 1000 

ppm (equivalent to18.5-24.0, 37.2-48.0, and 75.1- 97.8 mg/kg/day for males and 21.7-27.4, 43.0-

55.6, and 86.3-115.7 mg/kg/day for females). The test material was administered to P males and 

females for 10 weeks prior to mating. Dosing continued throughout the 2-week mating period, 

as well as during the resulting pregnancies and throughout lactation until weaning of the F1

offspring. The F1 generation was randomly selected on lactation day 21 to consist of 24 animals 

from each sex, direct treatment continued throughout the F1 maturation period (10 weeks). F1

animals also were administered the test material throughout the mating period, as well as during 

the resulting pregnancies and throughout lactation until weaning of the F2 offspring. 

Parental toxicity from exposure to BIT via diet was evident at 1000 ppm (75.1-97.8 mg/kg/day 

for males and 86.3-115.7 mg/kg/day for females) and 500 ppm (37.2-48.0 mg/kg/day for males 

and 43.0-55.6 mg/kg/day for females). Toxicity at 1000 ppm consisted of decreased mean body 

weight gains (F1 males and females), limiting ridge hyperplasia of the stomach (P and F1 males 

and females), squamous cell hyperplasia (P and F1 females), forestomach gastritis (F1 females), 
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keratosis (F1 females), and erosion/ulcer (F1 females). Toxicity at 500 ppm consisted of limiting 

ridge hyperplasia in the stomach (P and F1 males and females). Therefore, the parental toxicity 

NOAEL is determined to be 250 ppm (18.5-27.4 mg/kg/day for males and females), and the 

parental toxicity LOAEL is determined to be 500 ppm (37.2-48.0 mg/kg/day for males and 

43.0-55.6 mg/kg/day for females).

There was evidence for toxicity in offspring of animals exposed to 1000 ppm (75.1-97.8 

mg/kg/day for males and 86.3-115.7 mg/kg/day for females). At this dose, preputial separation 

in F1 male offspring and impaired growth and survival of pups of both sexes was observed. 

Therefore, the offspring LOAEL is determined to be 1000 ppm, and the offspring NOAEL 

is determined to be 500 ppm. 

This study is classified as acceptable- non-guideline. Concentration analyses of the diets 

administered to the second generation indicate that animals did not receive adequate doses of the 

test article during weeks 34 to 38 and/or the test diets may have contained an unknown

contaminant. However, the study does not need to be repeated because an additional study of 

this magnitude is unlikely to reveal reproductive toxic effects beyond those that were reported. 

The study can therefore be used for regulatory purposes, as dietary errors were not present until 

the last 4 weeks of the study, thus allowing sufficient time for the manifestation of reproductive 

effects that could be attributed to the test compound. 

In the second two-generation reproduction study (MRID 47759803), 1, 2 benzisothiazolin-3-one

(BIT; 89.8% a.i, batch/lot 2005-051) was administered to three groups of male and female 

Crl:CD(SD) rats (30/sex/group) daily by oral gavage at dose levels of 0, 10, 25, and 65/50 mg/kg 

bw/day. Mortality, clinical signs of excessive irritation, and reductions in food consumption and 

body weight gain were observed at 65 mg/kg/day, indicating that this dose exceeded the 

maximum tolerated dose. The high-dose was reduced to 50 mg/kg/day after the first 21 days of 

dosing, and was maintained at this lower level for the remainder of the F0 generation. This 

dosage level was also used as the high-dose for the F1 generation. One litter per dam was 

produced in each generation.

F0 animals were approximately 8 weeks of age at the initiation of test article administration. BIT 

was administered to offspring selected as the F1 parental generation following weaning (starting 

postnatal day [PND] 21). F0 and F1 parental males continued to receive the test article 

throughout mating and through the day prior to euthanasia. F0 and F1 parental females continued 

to receive the test article throughout mating, gestation and lactation, and through the day prior to 

euthanasia. 

Test article-related deaths occurred in the 25- and 65/50-mg/kg/day groups in the F0 generation 

and in the 50-mg/kg/day group in the F1 generation. Clinical findings for the majority of animals 

found dead or euthanized in extremis consisted of those related to the irritant properties of BIT, 

including gasping, rales, labored respiration, red material around the mouth, nose and/or eyes, 

and/or salivation. Microscopic findings of stomach lesions consisted mainly of hyperplasia and 

hyperkeratosis of the non-glandular (forestomach) mucosa in both F0 and F1 males and females at 

all dose level groups. These treatment-related changes were in a dose-related manner for 

incidence and severity. Other changes in the non-glandular mucosa that occurred in the highdose rats included submucosal inflammation, keratinous cysts, erosions, and ulcers. In the 
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glandular mucosa of the stomach, test article-relate changes included hyperplasia in the surface 

epithelium, erosions, and submucosal inflammation. Based on the test article-related deaths

observed at 25-mg/kg/day and 65/50-mg/kg/day, the adverse clinical signs observed in 

surviving animals and animals prior to death, and microscopic findings in the stomach in 

both F0 and F1 males and females at all dose levels, the parental systemic LOAEL for the F0

and F1 generations was 10 mg/kg/day. A NOAEL was not observed. 

Lower mean F0 body weight gains, food consumption, and food efficiency were observed in the 

65/50-mg/kg/day group males and females during the first 3 weeks of dosing at 65 mg/kg/day. 

Improvement was noted after the dosage level was lowered to 50 mg/kg/day; however, these 

early reductions in mean body weight gains resulted in lower overall mean body weight gains 

when the pre-mating period (males and females) and entire generation (males only) were 

evaluated. A test article-related lower mean body weight gain was also noted in the 50-

mg/kg/day F1 females during PNDs 22-29.

F0 and F1 reproductive parameters were not affected by BIT administration at any dosage level. 

There were no test article-related microscopic changes in any of the reproductive organs 

evaluated from the F0 and F1 generation rats at any dosage level. Based on the lack of effects 

on F0 and F1 reproductive parameters, a dosage level of 50 mg/kg/day was considered to be 

the NOAEL for parental reproductive toxicity. 

Mean numbers of F1 and F2 pups born, mean live litter sizes on PND 0, and offspring sex ratio 

were unaffected by BIT administration in both generations. Lower F1 postnatal survival was 

observed in the 65/50-mg/kg/day group, due in part to 2 F0 females with total litter loss. 

However, there were no test article-related effects on F2 postnatal survival in this group 

(offspring of females administered 50 mg/kg/day throughout the generation). No effects of 

parental test article administration were observed on the general physical condition of the pups in 

both generations or mean body weights and body weight gains. For pups found dead or 

euthanized in extremis, no test article-related macroscopic findings were noted. There were no 

test article-related effects on the organ weights of F1 or F2 pups on PND 21, or on the attainment 

of sexual developmental landmarks in F1 weanlings. Based on the lower F1 postnatal survival 

at the 65/50-mg/kg/day level, the NOAEL for neonatal toxicity was considered to be 25 

mg/kg/day.

This study is classified as Acceptable Guideline and satisfies the guideline requirements

(OPPTS 870.3800; OECD 416) for a two-generation reproduction study in the rat.

Chronic/ Carcinogenic Toxicity 

There are currently no data on file describing carcinogenicity of 1, 2-benzisothiazolin-3-one. 

However, based on extensive discussions with the registrants and with the Health Effects 

Division’s Hazard and Science Policy Council (HASPOC), the following conclusions are 

reached regarding the carcinogenicity of BIT (from the HASPOC memo dated May 3, 2012): 

“The HASPOC recommends, based on a weight of evidence (WOE) approach, that the chronic 

toxicity/carcinogenicity study for BIT is not required at this time if the risk assessment is 

protective of irritation. This recommendation was based on the following considerations: 1) 
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available cancer studies for the isothiazolone pesticides are negative; 2) there is a lack of 

mutagenicity concern for BIT and the other isothiazolone pesticides; 3) BIT and the other 

isothiazolones are irritants following oral, dermal, and inhalation exposures and produce similar 

effects following subchronic exposures; 4) the isothiazolones as a group have a known mode of 

action for antimicrobial activity; 5) irritation is the predominant effect and is the basis of the 

PODs; 6) although the metabolism study for BIT showed an increased half-life and accumulation 

of radioactivity in thyroid compared to other isothiazolone chemicals, these observations were 

determined to be not of toxicological significance, as the toxicological effects of BIT up to 90 

days were not different than the effects observed with the other isothiazolone chemicals.”

HASPOC also recommended that AD evaluate the available data to inform the need for an 

uncertainty factor to account for extrapolation from subchronic-to-chronic exposure durations for 

BIT. As long as the risk assessment addresses the potential irritation-like effects, chronic/cancer 

study requirements can be waived.

Mutagenicity 

Several mutagenicity studies are available for BIT, including a Salmonella typhimurium reverse 

mutation assay (MRID 47759804), an in vitro mammalian cells in culture gene mutation assay in

Chinese hamster ovary (CHO cells; MRID 47759805), an in vitro mammalian cytogenetics

chromosome aberration assay MRID 47759806), and an in vivo mammalian cytogenetics 

(erythrocyte micronucleus assay) in ICR mice (MRID 47759807). There was no evidence of 

mutagenicity for BIT in any of these studies. 

Immuntoxicity

There is currently no existing immunotoxicity study for BIT. This is a required study and has 

been identified as a data gap. The agency anticipates requiring this study. 

Metabolism Study

In a metabolism study (MRID 47759808), 14C-1,2-Benzisothiazolin-3-one ([BIT] radiolabeled 

at the benzene ring (Lot #s 1069.0003 and 1069.0004) was administered to (1) Sprague-Dawley 

rats (4/sex/dose) via single oral gavage at dose levels of 10 or 100 mg/kg and sacrificed at 96 

hours post-dosing; (2) another group of rats (3/sex) via oral gavage at dose level of 10 mg/kg 

14C-BIT and sacrificed at 1 hour post-dosing; (3) a repeat-dose group at dose level of 10 mg/kg 

14C-BIT once per day for 5 days and sacrificed at 96-hours after the final dose. One male rat 

and one female rat served as controls without being dosed with 14C-BIT. 

In the single-dose groups, the majority of 14C-BIT was excreted within 24 hours (89.30-

94.59%), mostly through urine (94.17 – 97.19% recovery in urine plus cage rinse) with a lesser 

amount found in the feces (1.87 – 4.18%). In the single dose 100 mg/kg group, the highest tissue 

concentrations of radioactivity (μg equivalents of BIT/g tissue) were found in adrenals, thyroids, 

and bone marrow, with higher concentrations (in these tissues) in females than males. In 

contrast, only the thyroid contained higher than the lower limit of quantitation (LLOQ) for 

radioactivity in the single low dose (10 mg/kg) group. 
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In the 10 mg/kg dose group, mean time to maximum concentration (Tmax) of radioactivity was 

1.7 hr in blood and 1 hr in plasma in both males and females. In the 100 mg/kg group, mean 

Tmax was 2.3 hr in blood and plasma for females and 3.0 hours in blood and plasma for males. 

Mean T1/2 values in blood were 3.7 and 4.7 hrs in the low dose males and females, respectively, 

and were 3.8 and 6.0 in high dose males and females, respectively. T1/2 values in plasma were 

2.3 and 2.6 hrs in the low dose males and females, respectively, and were 3.4 and 5.0 hrs in high 

dose males and females, respectively. These results indicated that high dose females had higher 

exposure to BIT-derived radioactivity compared to males. Concentration of radioactivity was 

similar in blood and plasma, indicating that there was no preferential difference in red blood 

cells.

BIT was extensively metabolized and primarily excreted through urine in the single-dose 

animals. Parent compound was not detected in urine or feces. Three metabolites, M1, M2, and 

M3, were identified in urine, with M3 having the highest proportion. In the feces, metabolites 

M1, M2, M3, and M4 were identified for the single-dose group. Proposed metabolic pathway 

includes a thiazolin-ring opening (between sulfur and nitrogen atoms) precursor (not detected), 

followed by glucuronyl (M1) or methyl (M4) conjugates, then di-oxidation of thioanisole (M4) 

resulted in the formation of M3 (sulfoxide), whereas mono-oxidation of M4 resulted in the 

formation of M2 (sulfone). The data presented for the single-dose groups satisfy the 

guideline requirement for a metabolism study OPPTS 870.7485, OECD 417 in rats. 

There are uncertainties for the repeated-dose group (group 6). The study report indicated that the 

majority of the radioactivity was recovered in the urine and cage rinse (90.92 – 91.50%) with the 

amount in feces ranging from 4.96-5.90%, and tissues contained less than 0.1% radioactivity at 

192 hours post-dose, which brought the total mean recovery of radioactivity to the range of 96.47 

– 96.83%. However, the data showed that the total identified percent distribution (% dose) of 

BIT metabolites in urine and feces for Group 6 was 16.38% and 15.78% for males and females, 

respectively, which was significantly lower than those for Group 1 (single low-dose) and Group 

3 (single high-dose). 

Toxicological Effects of Degradates.

See Appendix B, a number of degradates have been identified and characterized for the parent 

BIT. Structurally, these degrades are similar to the metabolites identified in the in vivo 

metabolism studies. There is no information indicating degradates can be more toxic than the 

parent compound. Therefore, the parent compound, BIT, will be used to assess the toxicity 

concern of its degradates.
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Appendix B Environmental Fate

Environmental Fate and Transport Properties of Benzisothazolin-3-

one and its degradate(s)

Water and Sediment

Hydrolysis

BIT is hydrolytically very stable for > 30 days under abiotic and buffered conditions at the three 

environmentally important pHs: 5, 7, and 9 (MRID# 4119901, 4418210).

Aqueous Photolysis

In aqueous photolysis, BIT is not stable and breaks down at pH 5, the half-life is 9 hours, while 

at pH 7, and 9, the half-life is 0.7 hours. Six photodegradation products were identified. In the 

30 day study, it was shown that these photodegradates also degrade to very low percentages by 

day 30. The photodegrates are oxidative metabolites, and form sulfur derived side chains

(MRID# 47329402).

Octanol-Water Partition Coefficient

The measured value of log Kow has been reported as 1.4. The value is much lower than the risk 

conern level (log Kow of 3.2). BIT is not likely to be bioaccumulative in aquatic species.

Soil

Soil Leaching/Adsorption/Desorption Batch Equilibrium

Adsorption/desorption study showed that Kd were in the range of 1.3-12.3 mg/g, which makes 

BIT to be mobile to moderately mobile in soils. Correspondingly, Koc were estimated at 254-728 

mg/g which shows similar trend as the Kd This tendency of mobility will take BIT move 

downward in soils, and possibly contaminate ground water. However, since BIT is also not 

stable on soil surfaces, and its half-life is 3.6 days, it the degradates rather than the parent that are

likely to reach the ground water (MRID# 41687102).

Aerobic Soil Metabolism

BIT metabolizes in soils under aerobic conditions with a short half-life of 3.6 days. A Three 

major metabolites were identified These metabolites are also oxidative metabolites. The Benzene 

skeleton of the parent is kept intact (MRID# 41199102, 41199103, 93053102). 
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A number of degradates have been identified and characterized for the parent BIT. 

The degradates of BIT are characterized through photolysis and soil metabolism studies: 

 BIT (1,2-benzisothiazol-3(2H)-one)

 

 2-sulfobenzamide

 1,2-benzthiazolin-2-one

 

Hydroxy-1,2-benzisothiazol-3-one
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Saccharin (1,2-benzisothiazolin-3-one-1,1-dioxide) 

The soil metabolism degradates include: 2-cabroamoylbenzene sulfonic acid, 1,2-

benzisothaizolin-3-one-1,1-dioxide and 1,2-benzthiazolin-3-one-1-oxide.

A number of similarities are evident with these degradates:

1. These are all oxidative degradates.

2. Benzene part of the structures remains intact.3.

3. The changes in the thiazolo part of the molecule is sulfonation, or sulfur oxidation.

4. Sulfonates, sulfoxides are known to degrade fast in the environmental media.

5. Due to structural similarities of the degradates to the parent, the reactivity and toxicity of 

the degradates should be equal to or less than the parent. These degradates are not likely 

to have additional adverse impact in the environmental media.

The agency anticipates that environmental fate data other than those studies anticipated as 

required for waste water treatment will not be required for these degradates.

If, however, stakeholders believe that submission of additional environmental fate data on the

degradates can streamline the environmental fate risk assessment of BIT, 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.
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Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Organisms

Birds

One acceptable acute-oral (LD50) study categorizes BIT as being moderately toxic to birds. The 

guideline (850.2100) is satisfied. Avian dietary studies (850.2200) are not required for BIT. 

However, one study was previously submitted and indicates that BIT is practically nontoxic 

when administered in the diet. No additional avian toxicity data are anticipated to be needed.

Avian Acute-oral and DietaryToxicity

Test Species Test Material

(% ai) Toxicity ToxicityCategory

EPA Study

ID

Northern bobwhite

(Colinus virginianus)

99 LD50 = 453mg ai/kg bw Moderately toxic 409913-01

Acceptable

72.2 LC50 >5620 ppm Practically nontoxic

417320-01

Acceptable

Nontarget Insects 

Toxicity data for beneficial insects (850.3020, 850.3030) are not needed to support the current 

use patterns, because BIT is not registered as a wood preservative. 

Toxicity to Aquatic Organisms

Freshwater Fish, acute

The available acute toxicity studies categorize technical-grade BIT as being moderately to highly 

toxic to freshwater fish. The guideline (850.1075) for acute toxicity testing is satisfied. 
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Acute Toxicity to Freshwater Fish

Test Species Test Material

(% ai)

Toxicity Endpoint

(mg ai/L)

Toxicity

Category

EPA Study

ID

Rainbow Trout

(Oncorhynchus 

mykiss)

73.62 LC50 = 1.3 Moderately toxic 455346-02

Acceptable

93 LC50 = 1.6 Moderately toxic 416871-01

Acceptable

89.9 LC50 = 1.9 Moderately toxic 473190-10

Acceptable

Bluegill

(Lepomis 

macrochirus)

93.2 LC50 = 0.54 Highly toxic 443649-13

Acceptable

Freshwater Invertebrates, acute

Four available acute toxicity studies categorize technical-grade BIT as being moderately to very 

highly toxic to freshwater invertebrates. The guideline (850.1010) for acute toxicity testing is 

satisfied. 

Acute Toxicity to Freshwater Invertebrates

Test Species Test Material

(% ai)

Toxicity Endpoint

(mg ai/L)

Toxicity

Category

EPA Study

ID

Water flea

(Daphnia magna)

73.62 EC50 = 1.5 Moderately toxic 455346-01

Acceptable

76.1 EC50 = 3.3 Moderately toxic 429490-01

Acceptable

89.8 EC50 = 3.7 Moderately toxic 473190-11

Acceptable

Freshwater Fish and Invertebrates, chronic

Two studies are available. NOAECs have been determined for both fish and aquatic invertebrates. No 

additional chronic data are expected to be needed for freshwater organisms (850.1300, 850.1400). 
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Chronic Toxicity to Freshwater Organisms

Species Test material

(% ai)

Toxicity

(mg ai/L or kg) Endpoint Status/MRID

Water column:

Fathead minnow

(Pimephales promelas)

89.8 NOAEC = 0.28

LOAEC = 0.59 Growth 477598-15Acceptable

Water flea

(Daphnis magna)

89.8

NOAEC = 0.91

LOAEC = 1.9

EC50 = 2.4

No. offspring;

Immobility

477598-14

Acceptable

Estuarine/Marine Fish and Invertebrates, acute

The available studies categorize technical-grade BIT as being slightly toxic to estuarine/marine 

fish and moderately to very highly toxic to invertebrates. The guidelines for acute toxicity to 

estuarine/marine fish (850.1075) and invertebrates (850.1025, 850.1035) are satisfied. No 

additional acute data are expected to be needed. 

Acute Toxicity to Estuarine/Marine Invertebrates

Test Species Test Material

(% ai)

Toxicity Endpoint

(mg ai/L)

Toxicity

Category

EPA Study

ID

Sheepshead minnow

(Cyprinodon 

variegatus)

76.1 LC50 = 12.2 Slightly toxic 429450-01

Acceptable

89.9 LC50 = 19 Slightly toxic 477598-13

Acceptable

Mysid shrimp

(Mysidopsis bahia)

76.1 LC50 = 0.99 Highly toxic 429490-02

Acceptable

89.8 LC50 = 1.8 Moderately 

toxic

477598-11

Acceptable

Pacific oyster

(Crassostrea gigas) 76.1 EC50 = 0.047 Very highly toxic

429524-01

Acceptable
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Estuarine/Marine Fish and Invertebrates, chronic

No chronic data are available for estuarine/marine fish (850.1400) or mysids (850.1350). 

Because the acute toxicity to the estuarine/marine fish is less than that of the freshwater fish and 

the mysid is comparable to the daphnid, the agency can use the acute: chronic ratio (ACR) from 

the freshwater species and the acute data to extrapolate the chronic NOAECs for the 

estuarine/marine organisms if values are needed for risk assessment. 

Aquatic Plants 

One supplemental study is available for a non-vascular species. A toxicity test using a vascular species 

(Lemna sp.) is anticipated to be needed (850.4400) to support all use patterns. To support Industrial 

Process and Water Systems use, toxicity tests also are anticipated to be needed for a green algae 

and freshwater diatom (850.4500) and for cyanobacteria (850.4550). If the green algae EC50 

from a Tier II test is less than 1 mg ai/L, the freshwater diatom and cyanobacteria tests would 

also be anticipated to be needed to support the Materials Preservative use pattern.

Toxicity to Aquatic Plants

Species Test material

(% ai)

Toxicity 

(mg ai/L)

Status/

MRID

Vascular:

Duckweed

(Lemna sp.) TGAI No data Outstanding

Non-Vascular:

Green algae

(Pseudokirchniriella subcapitata)

89.8 --

477598-17

Unacceptable1

Marine diatom

(Skeletonema costatum)

89.8 EC50 = 0.4 477598-18

Supplemental2

Freshwater diatom

(Navicula pelliculosa)

TGAI No data Outstanding

Cyanobacteria

(Anabaena flos-aqua)

TGAI No data Outstanding

1 BIT ai concentration was not provided; concentrations were based on nominal values

2 cell density in the control group was below guideline recommendations

Benthic Organisms

Based on the environmental fate properties of BIT (i.e., Kd <50 L/kg, Koc <1000), sediment toxicity 

testing (850.1735, 850.1740) is not anticipated to be required.
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Appendix C References

40991301 Roberts, N.; Phillips, C.; Howlett, C.; et al. (1988) The Acute Oral Toxicity of Proxel Press 

Paste to the Bobwhite Quail: Report No. ISN 164/88278. Unpublished study prepared by 

Huntingdon Research Centre. 37 p. 

41732001 Long, R.; Foster, J.; Hoxter, K.; et al. (1990) A Dietary LC50 Study With the Northern 

Bobwhite: Lab Project No. 123-162. Unpublished study prepared by Wildlife International 

LTD. 16 p. 

41687101 Brown, D. (1979) Proxel Press Paste: Determination of the Acute Toxicity to Rainbow 

Trout Salmo gairdneri: Lab Project Number: BL/B/1986. Unpublished study prepared by 

ICI Brixham Laborato- ry. 22 p. 

45534602 Scheerbaum, D. (1998) Fish (Rainbow trout), Acute Toxicity Test, 96 h, Semi-Static: 

Acticide BIT: Lab Project Number: 98702TS: FAR59991: FAR5999-. Unpublished study 

prepared by Dr U. Noack Laboratorium Fuer Angewandte Biologie. 50 p. {OPPTS 

850.1075} 

42949001 Kent, S.; Roberts, G.; Grinell, A. (1993) Proxel Press Paste: Acute Toxicity to Daphnia 

magna: Lab Project Number: BL4847/B: X060/B. Unpublished study prepared by Zeneca 

Ltd.'s Brixham Environmental Lab. 20 p. 

45534601 Noack, U. (1998) Aquatic Invertebrate Acute Toxicity Test (48 h), Freshwater Daphnids: 

Daphnia magna Straus: Acticide BIT: Lab Project Number: 9807012TS: DAI59991: 

DAI5999-. Unpublished study prepared by Dr. U. Noack Laboratorium fuer Angewandte 

Biologie. 55 p. {OPPTS 850.1010} 

42945001 Roberts, G.; Caunter, J.; Grinell, A. (1993) Proxel Press Paste: Acute Toxicity to 

Sheepshead minnow (Cyprinodon variegatus): Lab Project Number: BL4869/B: X060/A. 

Unpublished study prepared by Zeneca Limited, Brixham Environmental Lab. 20 p. 

42949002 Kent, S.; Roberts, G.; Stanley, R. (1993) Proxel Press Paste: Acute Toxicity to Mysid 

Shrimp (Mysidopsis bahia): Lab Project Number: BL4797/B: X060/C. Unpublished study 

prepared by Zeneca Ltd.'s Brixham Environmental Lab. 20 p. 

42952401 Roberts, G.; Caunter, J.; Johnson, P. (1993) PROXEL PRESS PASTE: Acute Toxicity to 

Larvae of the Pacific Oyster (Crassostrea gigas): Lab Project Number: BL4917/B. 

Unpublished study prepared by Brixham Environmental Lab, ZENECA Limited. 21 p. 

47319011 Palmer, S; Kendall, T.; Krueger, T.; et al. (2006) 1,2-Benzisothiazolin-3-one: A 48-Hour 

Flow-Through Acute Toxicity Test with the Cladoceran (Daphnia magna): Preventol BIT 

85 1,2-Benzisothiazolin-3-one. Project Number: 12A200, 06RC/084. Unpublished study 

prepared by Wildlife International, Ltd. 60 p.
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47759811 Palmer, S.; Kendall, T.; Krueger, H. (2007) 1,2-Benzisothiazolin-3-One: A 96-Hour FlowThrough Acute Toxicity Test with the Saltwater Mysid (Americamysis bahia): Final Report. 

Project Number: 129A/202, 06RC/085, 129/041806/MYS/96H2/100P/608. Unpublished 

study prepared by Wildlife International, Ltd. 60 p.

47319010 Palmer, S.; Kendell, T.; Krueger, H. (2006) 1,2-Benzisothiazolin-3-one: A 96-Hour FlowThough Acute Toxicity Test with the Rainbow Trout (Oncorhynchus mykiss): Preventol BIT 

85 1,2-Benzisothiazolin-3-one. Project Number: 129A/201, 06RC/082. Unpublished study 

prepared by Wildlife International, Ltd. 60 p.

47759814 Palmer, S.; Kendall, T.; Krueger, H. (2007) 1,2-Benzisothiazolin-3-One: A Flow-Through 

Life-Cycle Toxicity Test with the Cladoceran (Daphnia magna): Final Report. Project 

Number: 129A/204, 06RC/091. Unpublished study prepared by Wildlife International, Ltd. 

83 p.

47759815 Palmer, S.; Kendall, T.; Kruger, H. (2007) 1,2-Benzisothiazolin-3-One: An Early Life-Stage 

Toxicity Test with the Fathead Minnow (Pimephales promelas): Final Report. Project 

Number: 129A/205, 06RC/090. Unpublished study prepared by Wildlife International, Ltd. 

96 p.

44364913 Gilbert, J.L., Roberts, G.C. (1996) Acute Toxicity to Bluegill Sunfish (Lepomis macrochirus): 

Lab Project Number BL5701/B. Unpublished study prepared by Brixham Environmental 

Lab, ZENECA Specialties.
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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 BIT. 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 for acute effects were determined by dividing LC50 values 

(or EC50 values, if appropriate) from acute toxicity tests on aquatic vertebrates and invertebrates 

by 2. COCs for listed endangered and threatened aquatic organisms were determined by dividing 

LC50 values from acute toxicity tests on aquatic vertebrates and invertebrates by 20. COCs for 

chronic effects for non-listed and listed species were based on NOAEC values from tests on 

aquatic vertebrates and invertebrates. COCs for non-listed and listed aquatic plant species were 

determined by using the IC50 and NOAEC, respectively, from aquatic plant tests. In the absence 

of data on removal of BIT during wastewater treatment, no removal of BIT during wastewater 

treatment was assumed. 

The Down-the-Drain module was first run using a high-end scenario to determine whether the 

model predicted exceedances of concentrations of concern. If the high-end scenario predicted 

exceedances of the concentration of concern, the model was also run using the average scenario. 
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Appendix E Product Chemistry

The1,2-Benzisothiazolin-3-one (BIT)product chemistry information is summarized in Table E1 

(source: MRIDs 43584001, 41927501, 43584001, 42908201).

Table E1 – Product Chemistry of 1,2-Benzisothiazolin-3-one (BIT).

Guideline

Numbers Physical and Chemical Properties 1,2-Benzisothiazolin-3-one 

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 NMR; HPLC

830.1900 Submittal of samples CBI

830.6302 Color Off white to brown

830.6303 Physical State Solid

830.6304 Odor Little or no odor

830.6313

Stability

Stability to normal and elevated temperature, 

metals/metal ions 

Stable with respect to sunlight.

Stable with respect to normal and elevated 

temperatures.

Stable at 55oC for 14 days

Unstable with respect to copper metal and iron (III) ion.

830.6314 Oxidation/Reduction Neither an oxidizing nor a reducing agent.

Incompatible with strong oxidizers.

830.6315 Flammability Not Flammable

830.6316 Explodability Not Explodable

830.6320 Corrosion Characteristic No corrosion or discoloration was observed on 

packaging (Tests done with manufactured product)

830.7000 pH at25 °C 4.25 - 1% slurry

830.7050 UV/Visible Absorption Stable with respect to sunlight

830.7100 Viscosity Not applicable

830.7200 Melting point (°C) 159.5-160 oC 

830.7220 Boiling point(°C) Not applicable

830.7300 Density (g/cm3) 1.36±0.02 g/cm3

830.7370 Dissociation Constant pKa(s) Acid dissociation constant 9.12 x 10-8 moles/L (PAI)

pKa 7.04 at 25oC

830.7520 Particle size, fiber length, & diameter 

distribution Not reported

830.7550 Partition coefficient (n-octanol/water) Log Kow 1.4 (PAI)

830.7840 Solubility in water (mg/L) at 25 oC

1118 ppm at 20 oC

1380 ppm at 24 oC
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Guideline

Numbers Physical and Chemical Properties 1,2-Benzisothiazolin-3-one 

830.7860 Solubility in organic solvents

n-Hexane: 100 ppm at 23 oC

Ethyl acetate: 23000 ppm at 23 oC

Methanol: 67000 ppm at 24 oC

Acetonitrile: 13000 ppm at 23 oC

Acetone: 42000 ppm at 24 oC

Dichloromethane: 31000 ppm at 23 oC

Toluene: 5000 ppm at 24 oC

Heptane: 135 ppm at 20 oC

DMSO

830.7950 Vapor pressure (mm Hg) at 25 °C

Test done with PAI:

4.4 x 10-7 mm Hg at 20 oC

9.8 x 10-7 mm Hg at 25 oC