PRO-
Reregistration Eligibility
Decision (RED) for
Benzisothiazoline-3-one
September 29, 2005
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United States Office of Prevention, Pesticides 739-R-05-007
Environmental Protection and Toxic Substances September 2005
Agency (751OC)
Reregistration
Eligibility Decision for
1,2-Benzisothiazolin-3-one
(BIT)
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
This is to inform you that the Environmental Protection Agency (hereafter referred to as
EPA or the Agency) has completed its review of the available data and public comments
received related to the preliminary risk assessments for the antimicrobial l,2-benzisothiazolin-3-
one (hereafter referred to as BIT). The enclosed Reregistration Eligibility Decision (RED)
document was approved on September 29, 2005. Public comments and additional data received
were considered in this decision.
Based on its review, EPA is now publishing its Reregistration Eligibility Decision (RED)
and risk management decision for BIT and its associated human health and environmental risks.
A Notice of Availability will be published in the Federal Register announcing the publication of
the RED.
The RED and supporting risk assessments for BIT are available to the public in EPA's
Pesticide Docket OPP-2005-0200 at: http://www.epa.gov/edocket.
The BIT RED was developed through EPA's public participation process, published in
the Federal Register on July 20, 2005, which provides opportunities for public involvement in
the Agency's pesticide tolerance reassessment and reregistration programs. Developed with
input from EPA's advisory committees and others, the public participation process encourages
robust public involvement starting early and continuing throughout the pesticide risk assessment
and risk mitigation decision making process. The public participation process encompasses full,
modified, and streamlined versions that enable the Agency to tailor the level of review to the
level of refinement of the risk assessments, as well as to the amount of use, risk, public concern,
and complexity associated with each pesticide. Using the public participation process, EPA is
attaining its strong commitment to both involve the public and meet statutory deadlines.
Please note that the BIT risk assessment and the attached RED document concern only
this particular pesticide. This RED presents the Agency's conclusions on the dietary, drinking
water, occupational and ecological risks posed by exposure to BIT alone. This document also
contains both generic and product-specific data that the Agency intends to require in Data Call-
ins (DCIs). Note that DCIs, with all pertinent instructions, will be sent to registrants at a later
date. Additionally, for product-specific DCIs, the first set of required responses will be due 90
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days from the receipt of the DCI letter. The second set of required responses will be due eight
months from the receipt of the DCI letter.
As part of the RED, the Agency has determined that BIT will be eligible for reregistration
provided that all the conditions identified in this document are satisfied, including
implementation of the risk mitigation measures outlined in Section IV of the document. Sections
IV and V of this RED document describe labeling amendments for end-use products and data
requirements necessary to implement these mitigation measures. Instructions for registrants on
submitting the revised labeling can be found in the set of instructions for product-specific data
that accompanies this document.
Should a registrant fail to implement any of the risk mitigation measures outlined in this
document, the Agency will continue to have concerns about the risks posed by BIT. Where the
Agency has identified any unreasonable adverse effect to human health and the environment, the
Agency may at any time initiate appropriate regulatory action to address this concern. At that
time, any affected person(s) may challenge the Agency's action.
If you have questions on this document or the label changes necessary for reregistration,
please contact the Chemical Review Manager, Rebecca M. Miller, at (703) 305-0012.
Sincerely,
Frank T. Sanders
Director, Antimicrobials Division
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REREGISTRATION ELIGIBILITY
DECISION
for
l,2-Benzisothiazolin-3-one (BIT)
ListC
CASE 3026
Approved By:
Frank T. Sanders
Director, Antimicrobials Division
Attachment
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Table of Contents
BIT Reregistration Team i
Glossary of Terms and Abbreviations ii
Executive Summary iv
I. Introduction 1
II. Chemical Overview 3
A. Regulatory History 3
B. Chemical Identification 4
C. Use Profile 5
III. Summary of BIT Risk Assessments 6
A. Human Health Risk Assessment 6
1. Toxicity of BIT 6
2. FQPA Safety 9
3. Population Adjusted Dose (PAD) 10
a. Acute PAD 10
b. Chronic PAD 10
4. Dietary Exposure Assumptions 10
5. Dietary (Food) Risk Assessment 11
a. Acute and Chronic Dietary Risk 11
b. Dietary Exposure for Inert Ingredient Uses 12
c. Dietary Risk from Drinking Water 15
6. Residential Risk for Active Ingredient Uses 15
a. Toxicity 16
b. Residential Handler Scenarios 17
i. Exposure Scenarios, Data and Assumptions 17
ii. Residential Handler Risk Estimates 18
c. Residential Post-Application Exposure 19
i. Exposure Scenarios, Data and Assumptions 19
ii. Residential Post-Application Risk Estimates 19
7. Residential Risk for Inert Ingredient Uses 20
8. Aggregate Risk 22
a. Acute and Chronic Aggregate Risks 22
b. Short- and Intermediate- Term Aggregates Exposures
and Risks 23
9. Occupational Risk 26
a. Occupational Toxicity 26
b. Occupational Handler Exposure 27
c. Occupational Handler Risk Summary 28
d. Occupational Post-Application Exposure 29
B. Environmental Risk Assessment 30
1. Environmental Fate and Transport 30
2. Ecological Risk 30
3. Listed Species Consideration 32
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IV. Risk Management, Reregistration, and Tolerance Reassessment Decision... 34
A. Determination of Reregistration Eligibility 34
B. Public Comments and Responses 34
C. Regulatory Position 35
1. Food Quality Protection Act Findings 35
a. "Risk Cup" Determination 35
b. Determination of Safety to U.S. Population 35
c. Determination of Safety to Infants and Children 35
d. Cumulative Risks 36
e. Endocrine Disrupter Effects 36
2. Tolerance Summary 37
a. Tolerances Currently or Proposed to be Listed 37
b. Codex Harmonization 37
D. Regulatory Rationale 38
1. Human Health Risk Management 38
a. Dietary (Food) Risk Mitigation 38
b. Drinking Water Risk Mitigation 38
c. Residential Risk Mitigation 38
d. Occupational Risk Mitigation 39
i. Handler Exposure 39
ii. Post-Application Risk Mitigation 39
2. Environmental Risk Management 39
3. Listed Species Considerations 39
a. The Endangered Species Program 39
b. General Risk Mitigation 40
V. What Registrants Need to Do 41
A. Manufacturing Use Products 43
1. Additional Generic Data Requirements 43
2. Labeling for Technical and Manufacturing Use Products 43
B. End-Use Products 44
1. Additional Product-Specific Data Requirements 44
2. Labeling for End-Use Products 45
VI. Appendices 46
A. Table of Use Patterns for BIT 47
B. Table of Generic Data Requirements and Studies Used to Make the
Reregistration Decision 62
C. Technical Support Documents 67
D. Bibliography Citations 68
E. Generic Data Call-In 143
F. Product Specific Data Call-In 144
G. Batching of End-Use Products 145
H. List of All Registrants Sent the Data Call-In 150
I. List of Available Forms 151
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BIT Reregistration Team
Health Effects Risk Assessment
Melba Morrow
Cassi Walls
Tim McMahon
Michelle Centra
Timothy Leighton
Environmental Fate and Ecological Assessment
Najm Shamim
Kathryn Montague
Use Analysis
Rebecca Miller
Risk Management
Rebecca Miller
Registration Support
Karen Angulo
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GLOSSARY OF TERMS AND ABBREVIATIONS
a.i. Active Ingredient
aPAD Acute Population Adjusted Dose
APHIS Animal and Plant Health Inspection Service
ARTF Agricultural Re-entry Task Force
BCF Bioconcentration Factor
CDC Centers for Disease Control
CDPR California Department of Pesticide Regulation
CFR Code of Federal Regulations
ChEI Cholinesterase Inhibition
CMBS Carbamate Market Basket Survey
cPAD Chronic Population Adjusted Dose
CSFII USDA Continuing Surveys for Food Intake by Individuals
CWS Community Water System
DCI Data Call-In
DEEM Dietary Exposure Evaluation Model
DL Double layer clothing {i.e., coveralls over SL}
DWLOC Drinking Water Level of Comparison
EC Emulsifiable Concentrate Formulation
EDSP Endocrine Disrupter Screening Program
ED STAC Endocrine Disrupter Screening and Testing Advisory Committee
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an
environment, such as a terrestrial ecosystem.
EP End-Use Product
EPA U.S. Environmental Protection Agency
EXAMS Tier II Surface Water Computer Model
FDA Food and Drug Administration
FFDCA Federal Food, Drug, and Cosmetic Act
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FOB Functional Observation Battery
FQPA Food Quality Protection Act
FR Federal Register
GL With gloves
GPS Global Positioning System
HIARC Hazard Identification Assessment Review Committee
IDFS Incident Data System
IGR Insect Growth Regulator
IPM Integrated Pest Management
RED Reregistration Eligibility Decision
LADD Lifetime Average Daily Dose
LC50 Median Lethal Concentration. Statistically derived concentration of a substance expected to cause
death in 50% of test animals, usually expressed as the weight of substance per weight or volume
of water, air or feed, e.g., mg/1, mg/kg or ppm.
LCO Lawn Care Operator
LD50 Median Lethal Dose. Statistically derived single dose causing death in 50% of the test animals
when administered by the route indicated (oral, dermal, inhalation), expressed as a weight of
substance per unit weight of animal, e.g., mg/kg.
LOAEC Lowest Observed Adverse Effect Concentration
LOAEL Lowest Observed Adverse Effect Level
LOG Level of Concern
LOEC Lowest Observed Effect Concentration
mg/kg/day Milligram Per Kilogram Per Day
MOE Margin of Exposure
MP Manufacturing-Use Product
MRID Master Record Identification (number). EPA's system of recording and tracking studies
submitted.
MRL Maximum Residue Level
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N/A Not Applicable
NASS National Agricultural Statistical Service
NAWQA USGS National Water Quality Assessment
NG No Gloves
NMFS National Marine Fisheries Service
NOAEC No Observed Adverse Effect Concentration
NOAEL No Observed Adverse Effect Level
NPIC National Pesticide Information Center
NR No respirator
OP Organophosphorus
OPP EPA Office of Pesticide Programs
ORETF Outdoor Residential Exposure Task Force
PAD Population Adjusted Dose
PCA Percent Crop Area
PDCI Product Specific Data Call-In
PDF USDA Pesticide Data Program
PF10 Protections factor 10 respirator
PF5 Protection factor 5 respirator
PHED Pesticide Handler's Exposure Data
PHI Pre-harvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
PRZM Pesticide Root Zone Model
RBC Red Blood Cell
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RID Reference Dose
RPA Reasonable and Prudent Alternatives
RPM Reasonable and Prudent Measures
RQ Risk Quotient
RTU (Ready-to-use)
RUP Restricted Use Pesticide
SCI-GROW Tier I Ground Water Computer Model
SF Safety Factor
SL Single layer clothing
SLN Special Local Need (Registrations Under Section 24C of FIFRA)
STORET Storage and Retrieval
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TRAC Tolerance Reassessment Advisory Committee
TTRS Transferable Turf Residues
UF Uncertainty Factor
USDA United States Department of Agriculture
USFWS United States Fish and Wildlife Service
USGS United States Geological Survey
WPS Worker Protection Standard
ill
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EXECUTIVE SUMMARY
The Environmental Protection Agency (hereafter referred to as EPA or the Agency) has
completed its review of public comments on the human health and environmental risk
assessments for l,2-benzisothiazolin-3-one (hereafter referred to as BIT) and is issuing its risk
management decision. The Agency has decided BIT is eligible for reregistration provided all
measures outlined in this document are implemented. BIT is an antimicrobial that is used as an
industrial preservative for the protection of water-based adhesives, caulks, sealants, grouts,
spackling, ready-mixed cements, ready-mixed wallboard compounds, aqueous compositions
such as emulsion paints, aqueous slurries, home cleaning and car care products, laundry
detergents, fabric softeners, stain removers, inks, photographic processing solutions, paints and
stains, titanium dioxide slurries, oil in water emulsions, latices, metalworking fluids, casein/rosin
dispersions, textile spin-finish solutions, pesticide formulations, tape joint compound, leather
processing solutions, preservation of fresh animal hides and skins, and for offshore and terrestrial
gas/oil drilling muds and packer fluids preservation. l,2-Benzisothiazolin-3-one is also used as
an inert ingredient in a variety of products as a materials preservative. Exposures and risks from
the use of products containing l,2-benzisothiazolin-3-one as both the active and inert ingredients
are assessed in this reregistration eligibility decision (RED). End-use products are formulated as
either a soluble, ready-to-use, or flowable concentrates (all of which are considered to be
liquids).
Overall Risk Summary
The Agency's human health risk assessment indicates few risks of concern. Acute and
chronic dietary exposure is below the agency's level of concern for general U.S. populations and
all population subgroups. Likewise, it was concluded that risk from exposure of BIT in drinking
water would also not represent a risk of concern because it is not likely to be in drinking water
sources at substantial concentrations. This is based on the fact that BIT readily biodegrades, is
applied to crops via inert use in small amounts and is only likely to come into contact with
soil/surface water via paint uses in small amounts. The acute and chronic aggregate dietary risk
assessment estimates associated with the use of BIT as an inert or active ingredient are below the
Agency's level of concern.
Short and intermediate term residential post-application and handler exposures (dermal,
inhalation or incidental oral) from hard surface residues did not exceed the Agency's level of
concern. For residential exposure and risk, the toddler post-application dermal exposure scenario
from residues remaining on pets from the inert use, the margin of exposure (MOE) is below the
targeted MOE, indicating that this scenario is a risk of concern.
For aggregate exposure, the risk estimates associated with BIT are below the Agency's
level of concern. In cases where an aggregate risk index (ART) was used to assess risk because
of the different uncertainty factors for oral, dermal and inhalation exposure scenarios, the risk
indices suggested that there is reasonable certainty of no harm from using products containing
BIT. Based on the information provided, inhalation exposures were not considered to be of
concern with regard to inhalation risk from occupational handler scenarios; however the dermal
MOE indicated that the dermal risk for occupational handlers was below the target MOE for one
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scenario, handlers of BIT-containing paint using an airless sprayer. While the inhalation risk
may be an underestimation based on extrapolation from an oral study, the dermal risk is based on
a number of conservative assumptions and are not of concern. Dermal and inhalation exposures
to bystanders from the occupational use of BIT are also expected to be minimal.
The indoor uses of BIT make it unlikely that any appreciable exposure to terrestrial or
aquatic organisms would occur. Facilities using BIT for indoor industrial applications are
required to have NPDES permits before discharging effluents into receiving waters.
l,2-Benzisothiazolin-3-one's ready biodegradation in soil and small application amount
greatly reduce the exposure potential for terrestrial and aquatic organisms. Run-off into surface
water from pesticidal uses is likely to be low and it is not likely to be present in water sources at
substantial concentrations. The ecological risks from the use of BIT suggest that because of the
high toxicity of BIT to green algae and invertebrate species, adverse effects to the environment
could result from contamination from BIT-treated oil recovery fluids.
Dietary Risk
The Agency has conducted a dietary exposure and risk assessment for use of 1,2-
benzisothiazolin-3-one as a pulp and paper mill slimicide, and a preservative in paper coatings
and paper adhesives, all of which may end in indirect food contact scenarios. 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. Furthermore, given the conservative nature of the assumptions
used in the inert dietary exposure and risk assessment, risks of concern from food are not likely
from the use of l,2-benzisothiazolin-3-one as inert ingredients in pesticide products. A dietary
cancer risk assessment could not be performed as there are no carcinogenicity data for 1,2-
benzisothiazolin-3-one.
Drinking Water Risk
Based on environmental fate data, l,2-benzisothiazolin-3-one binds moderately with soil
and may potentially move with the soil during rainfall events and reach surface waters.
Although, l,2-benzisothiazolin-3-one has been shown to be hydrolytically stable with a half life
of > 30 days, it breaks down fairly quickly in aerobic soils. Outdoor use patterns of 1,2-
benzisothiazolin-3-one which may lead to contact with soil and/or surface water include: 1) the
application of agricultural pesticides that contain l,2-benzisothiazolin-3-one as an inert
ingredient, and 2) the application of paints that contain l,2-benzisothiazolin-3-one. Considering
l,2-benzisothiazolin-3-one readily biodegrades and the small amount (0.02 Ibs. per acre) that
may be applied to crops via the inert use and the small amount likely to come into contact with
soils/surface waters via the paint use, l,2-benzisothiazolin-3-one is not likely to be present in
drinking water sources at substantial concentrations.
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Residential Risk
To address residential exposure dermal, inhalation and incidental oral risks were assessed
for the active and inert ingredient uses of BIT. The residential handler scenarios evaluated are
considered to be representative of all possible exposure scenarios. None of the residential
handler exposure scenarios or post-application exposure scenarios exceeded the Agency's level
of concern.
For the inert uses of BIT, none of the residential handler exposure scenarios exceeded the
Agency's level of concern. Although most of the post-application exposures did not exceed the
Agency's level of concern, the toddler post-application dermal exposure scenario to residues
remaining on pets resulted in a MOE of 33 which is lower than the target MOE of 100 resulting
in risks of concern.
Aggregate Risk
The acute and chronic aggregate risk assessments generally include only dietary and
drinking water exposures. Since drinking water exposure is not expected from any of the indoor
or outdoor uses of l,2-benzisothiazolin-3-one used as either an inert or active ingredient, the
acute and chronic aggregate assessments only included dietary exposures from the active indirect
food uses (i.e., use in food-contact packaging) and inert dietary exposures from agricultural
pesticide uses. The acute and chronic aggregate risk estimates associated with 1,2-
benzisothiazolin-3-one are well below the Agency's level of concern where, the adult's risks
were 17.1% of the aPAD and 12.2% of the cPAD, and the children's risks were 44.1% of the
aPAD and 31.8% of the cPAD.
The short- and intermediate-term aggregate assessments were conducted for adults and
children. Since the toxicity endpoints for all of the routes of exposure (oral, dermal and
inhalation) are based on the same study and same toxic effect, all routes are aggregated together.
However, the aggregate risk index (ARI) method was utilized in the assessment. This method
was used because the oral, dermal and inhalation endpoints have different uncertainty factors that
need to be applied. For l,2-benzisothiazolin-3-one, all endpoints for exposure were derived from
a subchronic oral study in dogs however, the uncertainty factors (i.e., target MOEs) for oral,
dermal and inhalation routes are 300, 100 and 100, respectively. A risk index 1 indicates no
risk of concern. The short-term ARIs for adults and children were 6.8 and 1.9, respectively,
while the intermediate-term ARIs for adults and children were 7.5 and 1.9, respectively.
Therefore, short- and intermediate-term aggregate calculated risks are below the Agency's level
of concern. Please note that the inert use in pet products is considered to result in intermittent
exposures and, as such, were not included in the aggregate assessment.
Occupational Risk
To address occupational exposure, short-term inhalation, and intermediate-term
combined dermal and inhalation risks were assessed. The inhalation exposures are not of
concern for the any of the handler scenarios assessed (i.e., MOEs 1,000). However, for
handlers using BIT-treated paint via an airless sprayer, the dermal MOE of 90 indicates a risk of
concern (i.e., MOEs < 100).
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Postapplication exposures may occur in industrial settings around the water systems via
inhalation, and dermal exposures may occur while maintaining industrial equipment. However,
occupational post-application dermal and inhalation exposures to l,2-benzisothiazolin-3-one are
likely to be minimal when compared to handler exposure because of dilution during processing
or when compared to machinists using the metal working fluid. Inhalation exposures are
expected to be minimal because aerosol generation is not expected and the vapor pressure of 1,2-
benzisothiazolin-3-one is low.
Ecological Risk
Based on acute toxicity information, l,2-benzisothiazolin-3-one displays low to moderate
toxicity to birds and mammals. It is moderately toxic to freshwater fish and invertebrates,
slightly toxic to marine/estuarine fish, and highly toxic to marine/estuarine invertebrates.
The indoor uses of BIT considered in this RED make it unlikely that any appreciable
exposure to terrestrial or aquatic organisms would occur. Facilities using BIT for indoor
industrial applications are required to have NPDES permits before discharging effluents into
receiving waters. The potential exposure to terrestrial and aquatic species from the oil recovery
uses of BIT cannot be estimated at this time, as there is currently no validated model available
for such a purpose. The high toxicity of BIT to green algae and invertebrate species suggests that
potential adverse acute effects could occur to some species if environmental contamination from
BIT-treated oil recovery fluids occurs.
l,2-Benzisothiazolin-3-one is used as an inert ingredient in pesticide products but the
allowable amount that can be applied is small (not more than 0.1% formulation and 0.02 Ibs. per
acre). Data indicate that l,2-benzisothiazolin-3-one breaks down quickly in aerobic soils (half-
life < 24 hours in sandy loam soil). l,2-Benzisothiazolin-3-one's ready biodegradation in soil
and small application amount greatly reduce the exposure potential for terrestrial and aquatic
organisms. Run-off into surface water from pesticidal uses is likely to be low and it is not likely
to be present in water sources at substantial concentrations. Therefore, risk to nontarget
organisms is not anticipated from the inert uses of l,2-benzisothiazolin-3-one.
Listed Species
For certain use categories, the Agency assumes there will be minimal environmental
exposure, and only a minimal toxicity data set is required (Overview of the Ecological Risk
Assessment Process in the Office of Pesticide Programs U.S. Environmental Protection Agency -
Endangered and Threatened Species Effects Determinations, 1/23/04, Appendix A, Section IIB,
pg.81). Chemicals in these categories therefore do not undergo a full screening-level risk
assessment, and are considered to fall under a no effect determination. The active ingredient
uses of l,2-benzisothiazolin-3-one fall into this category.
The inert uses of l,2-benzisothiazolin-3-one are also considered to fall under a "no
effect" determination, for the following reasons:
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1. The allowable amount that can be applied is small (not more than 0.1% formulation
and 0.02 Ibs. per acre).
2. Data indicate that l,2-benzisothiazolin-3-one breaks down quickly in aerobic soils
(half-life < 24 hours in sandy loam soil).
3. l,2-Benzisothiazolin-3-one s ready biodegradation in soil and small application result
in minimal to no terrestrial or aquatic organism exposure.
Regulatory Decision
The Agency has completed its review and has determined that the data are sufficient to
support reregistration of all supported products containing BIT. The Agency is issuing this RED
for BIT, as announced in a Notice of Availability published in the Federal Register.
Summary of Mitigation Measures
The Agency has determined that BIT is eligible for reregistration provided the mitigation
measures described in this document are implemented.
Residential Risk
The Agency has concluded that to have an acceptable MOE for toddler dermal post-
application dermal scenarios, the maximum percent BIT as an inert in flea and tick pet products
is 0.033%. The Agency target MOE for this exposure scenario is 100, while the Agency
calculated toddler dermal post-application MOE is 33; a value that indicates a risk of concern.
All pet products containing BIT as an inert ingredient must contain a maximum of 0.033% BIT
in order mitigate the current risk that the flea and tick pet products pose.
Data Requirements
Additional confirmatory data is required to complete the reregistration of BIT. A
complete list of data gaps is presented Section V and Appendix B (Table of Generic Data
Requirements). In addition, product-specific data is required for all products containing BIT as
described in Section V of this document.
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I. Introduction
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988
to accelerate the reregistration of products with active ingredients registered prior to November
1, 1984 and amended again by the Pesticide Registration Improvement Act of 2003 to set time
frames for the issuance of Reregistration Eligibility Decisions. The amended Act calls for the
development and submission of data to support the reregistration of an active ingredient, as well
as a review of all submitted data by the U.S. Environmental Protection Agency (EPA or the
Agency). Reregistration involves a thorough review of the scientific database underlying a
pesticide's registration. The purpose of the Agency's review is to reassess the potential hazards
arising from the currently registered uses of the pesticide; to determine the need for additional
data on health and environmental effects; and to determine whether or not the pesticide meets the
"no unreasonable adverse effects" criteria of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into
law. This Act amends FIFRA to require tolerance reassessment. The Agency has decided that,
for those chemicals that have tolerances and are undergoing reregistration, the tolerance
reassessment will be initiated through this reregistration process. The Act also requires that by
2006, EPA must review all tolerances in effect on the day before the date of the enactment of the
FQPA. FQPA also amends the Federal Food, Drug, and Cosmetic Act (FFDCA) to require a
safety finding in tolerance reassessment based on factors including consideration of cumulative
effects of chemicals with a common mechanism of toxicity. This document presents the
Agency's revised human health and ecological risk assessments; and the Reregistration
Eligibility Decision (RED) for l,2-benzisothiazolin-3-one (BIT).
BIT is an antimicrobial that is used as an industrial preservative for the protection of
water-based adhesives, caulks, sealants, grouts, spackling, ready-mixed cements, ready-mixed
wallboard compounds, aqueous compositions such as emulsion paints, aqueous slurries, home
cleaning and car care products, laundry detergents, fabric softeners, stain removers, inks,
photographic processing solutions, paints and stains, titanium dioxide slurries, oil in water
emulsions, latices, metalworking fluids, casein/rosin dispersions, textile spin-finish solutions,
pesticide formulations, tape joint compound, leather processing solutions, preservation of fresh
animal hides and skins, and for offshore and terrestrial gas/oil drilling muds and packer fluids
preservation. The specific antimicrobial use categories include the following general use
patterns: material preservatives (indoor food and indoor/outdoor non-food), industrial processes
and water systems (indoor nonfood), and indoor and outdoor residential uses. 1,2-
Benzisothiazolin-3-one is also used as an inert ingredient in a variety of products as a materials
preservative. Exposures and risks from the use of products containing l,2-benzisothiazolin-3-
one as both the active and inert ingredients were assessed.
The Agency has concluded that the FQPA Safety Factor for l,2-benzisothiazolin-3-one
should be removed (equivalent to IX) based on (1) the lack of evidence of increased
susceptibility in the 2-generation reproduction toxicity study and the available developmental
toxicity data; and (2) the risk assessment does not underestimate the potential risk for infants
and children.
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Risks summarized in this document are those that result only from the use of the active
ingredient l,2-benzisothiazolin-3-one. The Food Quality Protection Act (FQPA) requires that
the Agency consider available information concerning the cumulative effects of a particular
pesticide's residues and other substances that have a common mechanism of toxicity. The
reason for consideration of other substances is due to the possibility that low-level exposures to
multiple chemical substances that cause a common toxic effect by a common toxic mechanism
could lead to the same adverse health effect that would occur at a higher level of exposure to any
of the substances individually. 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 for l,2-benzisothiazolin-3-one and any other substances. 1,2-
benzisothiazolin-3-one does not appear to produce a toxic metabolite produced by other
substances. For the purposes of this action, therefore, EPA has not assumed that 1,2-
benzisothiazolin-3-one has a common mechanism of toxicity with other substances. For
information regarding EPA's efforts to determine which chemicals have a common mechanism
of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements
released by EPA's Office of Pesticide Programs concerning common mechanism determinations
and procedures for cumulating effects from substances found to have a common mechanism on
EPA's website at http://www.epa.gov/pesticides/cumulative.
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of BIT. In an effort to simplify the RED, the information presented herein is
summarized from more detailed information that can be found in the technical supporting
documents for BIT referenced in this RED. The revised risk assessments and related addenda
are not included in this document, but are available in the Public Docket at
http ://www. epa. gov/edocket.
This document consists of six sections. Section I is the introduction. Section II provides
a chemical overview, a profile of the use and usage of BIT, and its regulatory history. Section
III, Summary of BIT Risk Assessment, gives an overview of the human health and
environmental assessments, based on the data available to the Agency. Section IV, Risk
Management, Reregistration, and Tolerance Reassessment Decision, presents the reregistration
eligibility and risk management decisions. Section V, What Registrants Need to Do, summarizes
the necessary label changes based on the risk mitigation measures outlined in Section IV.
Finally, the Appendices list all use patterns eligible for reregistration, bibliographic information,
related documents and how to access them, and Data Call-In (DCI) information.
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II. Chemical Overview
A. Regulatory History
There are 43 active products containing l,2-benzisothiazolin-3-one as an active
ingredient, 3 of which are technical products, registered under Section 3 of the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA). There are hundreds of products that have
inert uses for l,2-benzisothiazolin-3-one. The first product containing l,2-benzisothiazolin-3-one
was registered on April 4, 1973.
B.
Chemical Identification - Technical BIT
Common name: BIT
Chemical name: l,2-Benzisothiazolin-3-one
Chemical Family: Isothiazolines
Empirical formula: CyHsNOS
CAS Registry No.: 2634-33-5
Case number: 3026
OPP Chemical Code: 098901
Molecular weight: 151.9
Trade name(s): IPX, Proxan, Proxel, Nipacide BIT, Mergal BIT
Basic manufacturer: PromChem, Arch Chemicals, ISP, Clariant Corp., and Troy Corp.
Technical BIT is in the form of a solid paste and is off-white to brown in color. BIT has
a melting point of 159.5-160°C. Three separate water solubilities were provided by different
registrants: 1118 ppm at 20°C, 1380 ppm at 24°C, EPA database (EPI Suite) lists the solubility of
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2.1 g/L at 25 ° C. BIT has a vapor pressure of 4.4 x 10"7mm Hg at 20°C, 9.8 x 10"7mm Hg at
25°C, and 2.78 x 10'6 mm Hg at 25°C
C. Use Profile
The following is information on the currently registered uses of BIT products and an
overview of use sites and application methods. A detailed table of the uses of BIT eligible for
reregistration is contained in Appendix A.
Type of Pesticide: Fungicide/Fungistat
Bacteriostat
Microbicide/Microbistat
Disinfectant (Bacteriocide/Germicide)
Summary of Use:
Food: BIT is used as an inert ingredient on many crops including Caneberries,
Blackberries, Blueberries, Cranberries, Strawberries, Citrus, Almond, Apples,
Pears, Apricots, Cherries, Nectarines, Peaches, Plums, Prunes, Cantaloupes,
Casaba Melons, Crenshaw Melons, Honeydew Melons, Muskmelons,
Watermelons, Tomatoes, Broccoli, Brussel Sprouts, Cabbage, Cauliflower,
Collards, Kale, Endive, Spinach, Lettuce, Carrots, Onions, Radishes, Rutabagas,
Guar, Ginseng, Beets, and Mustard.
Non-Food: BIT is also used as an inert ingredient on Conifer Plantings, Ornamental
Flowering Plants, Ornamental Lawns, Ornamental Woody Shrubs, Roses, English
Ivy, Ornamental Trees, Weeping Fig, Elm, Oak, Palm, Arizona Cypress, and Irish
Moss.
Residential: BIT is used as an active ingredient for Nonagricultural Buildings, Perimeter Soil
Treatment, Domestic Dwellings (Outdoor), and Hard Nonporous Surfaces.
Industrial: BIT is used as an active ingredient for Pulp and Paper Mill Systems, Secondary
Oil Recovery Injection Water, and Heat Exchanger Water.
Materials Preservatives:
BIT is used as an active ingredient for Adhesives, Preservative Incorporation,
Adhesives (Gums, Joint Cements, Latex, Tape Muds, Protein based, Starch based,
Synthetic), Caulking Compounds, Grouts, Starch, Wallboard Joint Compounds,
Mastics, Sealants, Coatings (Aqueous, Lacquer, Rosin, Wood, Protein and Starch
based), Films, Coatings (Paper, Paper Products and Paperboard), Hides and
Leather Products, Leather Processing Liquors (Preservative Incorporation),
Metalworking Cutting Fluids (Preservative Incorporation), Oil Recovery Drill
Muds and Packer Fluids (Preservative Incorporation), Paints (Acrylic, Emulsion
and Latex), Synthetic Polymers, Latex and Latex Emulsions, Resin Emulsions,
Cleansers, Photographic Solution, Polishes, Soap, Wax, Inks, Liquid Detergents,
Dyes, Powdered Detergents, Floor Wax, Fabric Softeners, Tarnish Agents, Air
Fresheners, Carpet Shampoos, Canvas, Cordage, rope, twine, Fabrics, Casein,
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Clay Slurries, Starch Solutions, Printing Pastes, Stains (preservative
incorporation), Water Based Paints, and Concrete Mixtures.
Target Pests: Staphylococcus aureus, pseudomonas aeruginosa, rhizopus stolonifer, aspergillus
pencilloides, aspergillus niger, alternaria radicina, tricophyton mentagrophytes,
salmonella typhosa, klebsiella pneumoniae, bacillus subtilis, bacillus megaterium,
eschericha coli, proteus vulagris.
Formulation Types: Granular powder, flowable concentrate, soluble concentrate, ready to use
solution.
Method and Rates of Application:
All products containing BIT as an active ingredient, including ready-to-use
solutions, are used in manufacturing processes only. For laundry detergents,
household cleaning products, and car care products, 0.10% to 0.30% of BIT is
added by weight. When used as a materials preservative, 0.05% to 1% of BIT is
added by weight. Please refer to Appendix A for more detailed application rates.
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III. Summary of BIT Risk Assessments
The purpose of this summary is to assist the reader by identifying the key features and
findings of these risk assessments, and to help the reader better understand the conclusions
reached in the assessments. The human health and ecological risk assessment documents and
supporting information listed in Appendix C were used to formulate the safety finding and
regulatory decision for BIT. While the risk assessments and related addenda are not included in
this document, they are available from the OPP Public Docket and may also be accessed on the
Agency's website at http ://epa. gov/docket. Hard copies of these documents may be found in the
OPP public docket under docket number OPP-2004-0200. The OPP public docket is located in
Room 119, Crystal Mall II, 1801 Bell Street, Arlington, VA, and is open Monday through
Friday, excluding Federal holidays, from 8:30 a.m. to 4:00 p.m.
A. Human Health Risk Assessment
1. Toxicity of BIT
A brief overview of the toxicity studies used for determining endpoints in the human
health dietary risk assessments are outlined in Table 2. Further details on the toxicity of BIT can
be found in the documents "Human Exposure Assessment for a Reregistration Submission for
l,2-Benzisothiazolin-3-one (BIT)," dated July 11, 2005; "Dietary Risk Assessment of 1,2-
Benzisothiazolin-3-one (BIT) for Reregistration Eligibility Decision (RED) Document," dated
July 12, 2005; and "l,2-Benzisothizolin-3-one (BIT)-Revised Report of the Antimicrobials
Division's Toxicology Endpoint Selection Committee (ADTC)," dated April 22, 2005. These
documents are available on Agency's website in the EPA Docket at http://www/epa.gov/edocket.
The Agency has reviewed all toxicity studies submitted for BIT and has determined that
the toxicological database is sufficient for reregistration. The studies have been submitted to
support guideline requirements. Major features of the toxicology profile are presented below.
Acute toxicity data show that l,2-benzisothiazolin-3-one is moderately toxic by the oral and
dermal routes (Toxicity Category III for both studies), but that this chemical is a severe eye
irritant (Toxicity Category I). Irritation to the skin from acute data show only mild skin irritation
(Toxicity Category IV), but repeated dermal application indicated a more significant skin
irritation response.
Table 1. Acute Toxicity of l,2-Benzisothiazolin-3-one Technical
Guideline
No.
870.1100
870.1200
870.1300
Study Type
Acute Oral
Acute Dermal
Acute Inhalation
MRID #(s)
41022101;
42858101
41022102;
42858102
Results
LD50 = 670 mg/kg
(M); 784 mg/kg (F)
LD50 > 2000 mg/kg
Toxicity
Category
III
III
waiver granted
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Guideline
No.
870.2400
870.2500
870.2600
Study Type
Primary Eye
Irritation
Primary Skin
Irritation
Dermal
Sensitization
MRID #(s)
42905102
42905101
41750001;
42858103
Results
severe eye irritant
slight irritant
moderate dermal
sensitizer
Toxicity
Category
I
IV
Not Applicable
The doses and toxicological endpoints selected for the dietary exposure scenarios are
summarized in Table 2 below.
Table 2. Toxicological Endpoints for BIT (Dietary)
Exposure
Scenario
Dose Used in Risk
Assessment
(mg/kg/day)
Target MOE, UF,
Special FQPA SF, for
Risk Assessment
Study and Toxicological Effects
Acute Dietary
General
NOAEL= 5 mg/kg/day
population,
including infants
and children
UF = 100 (lOx inter-species
extrapolation, lOx intra-
species variation)
FQPA SF= 1
DB UF = 3
Acute 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.
and
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.
Chronic Dietary
All populations
NOAEL= 5 mg/kg/day
UF = 100 (lOx inter-species
extrapolation, lOx intra-
species variation)
FQPA SF= 1
DB UF = 3
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.
and
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.
Cancer: No cancer data available for l,2-benzisothiazolin-3-one
UF = uncertainty factor, FQPA SF = Special FQPA safety factor, NOAEL = no observed adverse effect level,
LOAEL = lowest observed adverse effect level, PAD = population adjusted dose, (a = acute, c = chronic) RfD
reference dose, MOE = margin of exposure, N/A = Not Applicable
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Developmental toxicity studies were conducted in rats with maternal effects including
decreased body weight gain, decreased food consumption, and clinical toxicity signs (audible
breathing, haircoat staining of the anogenital region, dry brown material around the nasal area) as
well as increased mortality. Developmental effects consisted of increases in skeletal
abnormalities (extra sites of ossification of skull bones, unossified sternebra) but not external or
visceral abnormalities.
In a two- generation reproduction study, parental toxicity was observed at 500 ppm and
was characterized by lesions in the stomach. In pups, toxic effects were reported at 1000 ppm
and consisted of preputial separation in males and impaired growth and survival in both sexes.
The reproduction study did not show evidence of increased susceptibility of offspring.
General Toxicity Observations
Subchronic oral toxicity studies showed systemic effects after repeated oral
administration including decreased body weight, increased incidence of forestomach hyperplasia,
and non-glandular stomach lesions in rats. In dogs, the effects occurred at lower doses than in
rats, and included alterations in blood chemistry (decreased plasma albumin, total protein, and
alanine aminotransferase) and increased absolute liver weight.
The Agency has concluded that there is not a concern for neurotoxicity resulting from
exposure to l,2-benzisothiazolin-3-one. The neurotoxicity observed in the rat acute oral toxicity
study (piloerection and upward curvature of the spine at 300 mg/kg and above; decreased
activity, prostration, decreased abdominal muscle tone, reduced righting reflex, and decreased
rate and depth of breathing at 900 mg/kg) and the acute dermal toxicity study (upward curvature
of the spine was observed in increased incidence, but this was absent after day 5 post-dose at a
dose of 2000 mg/kg) were felt to be at exposures in excess of those expected from the use pattern
of this pesticide and that such effects would not be observed at estimated exposure doses.
Dietary: The acute and chronic RfDs are 0.017 mg/kg/day. These endpoints are based on
a subchronic toxicity study in dogs with a reported NOAEL of 5 mg/kg/day and which indicated
increased incidences of emesis and clinical chemistry alterations at the LOAEL of 20 mg/kg/day.
An uncertainty factor of 300 (1 Ox for interspecies extrapolation, lOx for intraspecies variability,
and 3x for database uncertainty) was applied to the NOAEL to obtain the acute and chronic
RfDs. The data base uncertainty factor of 3x is applied to account for oral data base concerns
based on the lack of reliable developmental toxicity data with respect to maternal toxicity.
Incidental Oral: The short- and intermediate-term oral endpoint is 5 mg/kg/day and is
based on increased incidence of emesis and clinical chemistry alterations at 20 mg/kg/day in a
subchronic toxicity study in dogs. The target margin of exposure (MOE) is 300.
Dermal: The short-, intermediate-, and chronic-term dermal endpoint is 5 mg/kg/day and
is based on increased incidence of emesis and clinical chemistry alterations at 20 mg/kg/day in a
subchronic toxicity study in dogs. The target MOE is 100 for residential and occupational
exposure.
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Inhalation: The short-, intermediate-, and chronic-term inhalation endpoint is 5
mg/kg/day and is based on increased incidence of emesis and clinical chemistry alterations at 20
mg/kg/day in a subchronic toxicity study in dogs. The target MOE is 100 for occupational and
residential exposure; however if the resulting MOE is not at least 1000, the Agency can request a
repeat dose inhalation study of at least 28 days in duration. (The MOE of 1000 is based on the
application of a 1 OX uncertainty factor for interspecies extrapolation, a 10X uncertainty for
intraspecies variability and a 10X for the lack of an inhalation study).
Dermal Penetration: A dermal penetration study was conducted in rats in which a
lOmg/kg dermal dose of l,2-benzisothiazolin-3-one was applied to the skin for durations of 4, 8,
24, 48 or 72 hours. At 72 hours a maximum dermal penetration of 40.6% was achieved.
Mutagenicity: All acceptable mutagenicity studies showed a negative mutagenic
response for this chemical.
Carcinogenicity: Carcinogenicity data are not available for l,2-benzisothiazolin-3-one.
These data are required to support the metalworking fluid use.
Endocrine Disruption Potential: EPA is required under the Federal Food Drug and
Cosmetic Act (FFDCA), as amended by FQPA, to develop a screening program to determine
whether certain substances (including all pesticide active and other ingredients) "may have an
effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other
such endocrine effects as the Administrator may designate. When the appropriate screening
and/or testing protocols being considered under the Agency's Endocrine Disrupting Screening
Program (EDSP) have been developed, l,2-benzisothiazolin-3-one may be subjected to
additional screening and/or testing to better characterize effects related to endocrine disruption.
2. FQPA Safety Factor
The FQPA Safety Factor (as required by the Food Quality Protection Act of 1996) is
intended to provide an additional 10-fold safety factor (10X), to protect for special sensitivity in
infants and children to specific pesticide residues in food, drinking water, or residential
exposures, or to compensate for an incomplete database. The FQPA Safety Factor has been
removed (i.e., reduced to IX) for l,2-benzisothiazolin-3-one based on (1) the lack of evidence
of increased susceptibility in the 2-generation reproduction toxicity study and the available
developmental toxicity data; and (2) the risk assessment does not underestimate the potential
risk for infants and children. The FQPA Safety Factor assumes that the exposure databases
(food, drinking water, and residential) are complete, the risk assessment for each potential
exposure scenario includes all metabolites and/or degradates of concern, and does not
underestimate the potential risk for infants and children. These criteria have been met for 1,2-
benzisothiazolin-3-one. Based on the analysis of submitted developmental toxicity studies, the
Agency determined that no special FQPA Safety Factor was needed since there were no residual
uncertainties for pre- and/or postnatal toxicity.
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3. Population Adjusted Dose (PAD)
Dietary risk is characterized in terms of the Population Adjusted Dose (PAD), which
reflects the reference dose (RfD), either acute or chronic, that has been adjusted to account for
the FQPA Safety Factor (SF). This calculation is performed for each population subgroup. A
risk estimate that is less than 100% of the acute or chronic PAD is not of concern.
a. Acute PAD
Acute dietary risk for BIT is assessed by comparing acute dietary exposure estimates (in
mg/kg/day) to the acute Population Adjusted Dose (aPAD). Acute dietary risk is expressed as a
percent of the aPAD. The aPAD is the acute reference dose (0.017 mg/kg/day) modified by the
FQPA safety factor. The acute reference dose was derived from a subchronic toxicity study in
dogs in which both the NOAEL (5.0 mg/kg/day) and the LOAEL (20.0 mg/kg/day) were
determined based on the incidence of emesis and clinical chemistry alterations in both sexes.
This study was further supported by a subchronic toxicity study in rats in which both the
NOAEL (8.42 mg ai/kg/day) and the LOAEL (25.26 mg ai/kg/day) were determined based on
the incidence of macroscopic and microscopic lesions in both sexes. The BIT aPAD is 0.017
mg/kg/day based on a reference dose of 0.017 mg/kg/day, and incorporating the FQPA safety
factor of IX for the overall U.S. population or any population subgroups.
b. Chronic PAD
Chronic dietary risk for BIT is assessed by comparing chronic dietary exposure estimates
(in mg/kg/day) to the chronic Population Adjusted Dose (cPAD). Chronic dietary risk is
expressed as a percent of the cPAD. The cPAD is the chronic reference dose (0.017 mg/kg/day)
modified by the FQPA safety factor. The cPAD was derived from a subchronic toxicity study in
dogs in which both the NOAEL (5.0 mg/kg/day) and the LOAEL (20.0 mg/kg/day) were
determined based on the incidence of emesis and clinical chemistry alterations in both sexes.
This study was further supported by a subchronic toxicity study in rats in which both the
NOAEL (8.42 mg ai/kg/day) and the LOAEL (25.26 mg ai/kg/day) were determined based on
the incidence of macroscopic and microscopic lesions in both sexes. The BIT cPAD is 0.017
mg/kg/day based on a reference dose of 0.017 mg/kg/day, which includes the incorporation of
the FQPA safety factor (IX) for the overall U.S. population or any population subgroups.
4. Dietary Exposure Assumptions
Dietary exposure to BIT residues occurs primarily from the antimicrobial paper uses
which include: slimicide use in paper/pulp manufacturing, paper coatings preservative, and paper
adhesive preservatives. Acute and chronic dietary exposure assessments were conducted using
FDA's Center for Food Safety & Applied Nutrition's (CFSAN) screening-level approach as
presented in "Preparation of Food Contact Notifications and Food Additive Petitions for Food
Contact Substances: Chemistry Recommendations" dated April 2002. Using the maximum
application rates and US FDA's default assumptions, "worst-case" dietary concentration values
were calculated by the Agency.
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FDA's method utilizes a number of general assumptions for calculating the amount of
BIT in food from contacting treated paper surfaces. These assumptions include the following: 1)
the food contact can result from a one time use or a repeat use of the paper; 2) the consumption
factor (CF or fraction of food that contacts the packaging surface) represents a ratio of the actual
weight of food that comes into contact with the paper packaging to the total weight of the food
packaged with the paper; 3) the CF varies based on type of packaging; and 4) 100% of the
antimicrobial present in the packaging migrates into the food commodities.
5. Dietary (Food) Risk Assessment
a. Acute and Chronic Dietary Risk
Generally, a dietary risk estimate that is less than 100% of the acute or chronic PAD does
not exceed the Agency's risk concerns. Since the PADs for acute and chronic exposures are
identical, the dietary risk estimates are the same for both durations of exposure in this case. A
summary of acute and chronic risk estimates are shown in Table 3.
Risk estimates are below the Agency's level of concern. For adults, the combined acute
and chronic dietary risk estimate is 9.4% of the acute PAD and chronic PAD. For children, the
most highly exposed population subgroup, the combined acute and chronic dietary risk estimate
is 21.8% of the acute PAD and chronic PAD. Therefore, acute and chronic dietary risk estimates
are below the Agency's level of concern for all population subgroups.
Table 3. Summary of Dietary Exposure and Risk for l,2-Benzisothiazolin-3-one
Population
Subgroup
EDI
( g/person/day)
Acute and Chronic Dietary
Dietary
Exposure3
(mg/kg/day)
Slimicide
Adult
Child
14.1
7.05
% aPAD and
% cPAD b
0.0002
0.00047
1.2
2.8
Paper Adhesive Preservative
Adult
Child
21.0
10.5
0.0003
0.0007
1.8
4.1
Paper Coating Preservative
Adult
Child
75.0
37.5
0.0011
0.0025
6.5
14.7
11
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Population
Subgroup
EDI
( g/person/day)
Acute and Chronic Dietary
Dietary
Exposure3
(mg/kg/day)
% aPAD and
% cPAD b
Combined
Adult
Child
110.1
55.1
0.0016 9.4
0.0037 21.8
a~ For adults, acute and chronic exposure analysis is based on a body weight of 70 kg. For children, exposure is
based on a body weight of 15 kg.
b~%PAD = dietary exposure (mg/kg/day) * 100 / aPAD or cPAD, where aPAD and cPAD for adults and children =
0.017 mg/kg/day
b. Dietary Exposure for Inert Ingredient Uses
Included in this RED is the reassessment of l,2-benzisothiazolin-3-one when used as an
inert ingredient in pesticide products. l,2-Benzisothiazolin-3-one is used as a
preservative/stabilizer in a wide variety of residential use and agricultural pesticide products,
including outdoor yard, garden, and turf products, and agricultural crop products.
Inert Dietary Exposure Assumptions
A dietary exposure analysis for the inert ingredient use of l,2-benzisothiazolin-3-one was
conducted using the generic screening model for estimating inert ingredient dietary exposure as a
basis for estimating l,2-benzisothiazolin-3-one dietary exposure. The generic model's output
was adjusted to reflect the tolerance exemption limitation given in 40 CFR §180.920 which
states that l,2-benzisothiazolin-3-one cannot be applied at more than 0.02 Ibs per acre. The
generic screening model does not specifically include an application rate input, rather it is based
on tolerances for pesticide active ingredients with application rates generally ranging from 1 to 5
Ib ai/acre. Therefore, to more accurately estimate residues resulting from the lower application
rate limitation of 0.02 Ibs/acre of l,2-benzisothiazolin-3-one, the results from the generic model
were adjusted by a factor of 50 (using the ratio of 1 Ib. per acre + 0.02 Ibs per acre) and 250
(using the ratio of 5 Ibs. per acre + 0.02 Ibs/acre) to reflect residue levels resulting from the
specified maximum application rate of l,2-benzisothiazolin-3-one.
The dietary assessment is unrefined and extremely conservative in nature because the
screening model assumes that the inert ingredient is used on all commodities, and that 100
percent of crops are treated with the inert ingredient. Further, the model assumes residues will
be present for every consumed commodity (including meat, milk, poultry and eggs) that is
included in the Dietary Exposure Evaluation Model (DEEM). Additionally, in the case of 1,2-
benzisothiazolin-3-one, the choice of an adjustment factor based on maximum application rate is
conservative in nature, because the use of an adjustment factor based on concentration in
formulation results in exposures less than half of the lowest values for the U.S. population and all
population subgroups reported in Tables 8 and 9.
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Inert Dietary Risk from Food
The tables below provide a summary of the results of the acute and chronic dietary risk
estimates for l,2-benzisothiazolin-3-one. Only one population subgroup had an estimated
exposure over 100 % of either PADs at the 95th percentile of exposure - "Children (1-2 years)"
had 112% of the aPAD but this was only at the high end of exposure. Considering the unrefined
and extremely conservative nature of this screening level model (e.g., inclusion of all
commodities; 100% of commodities are treated; adjustment factor for application rate), the
results for all population subgroups are considered not to be of concern.
It should be noted that while the results from the screening level model do not raise a
dietary concern, the modeling results would be even lower if an alternate adjustment factor had
been used. As described in the "Exposure Assumptions" section above, l,2-benzisothiazolin-3-
one's maximum application rate of 0.02 Ibs/acre was adjusted by 50 and 250 in the generic
model. Instead of adjusting for application rate, the model could have been adjusted for the
concentration of l,2-benzisothiazolin-3-one in the pesticide formulation, which is limited to a
maximum of 0.1% under 40 CFR §180.920 (the proposed tolerance exemption for use on
animals under 180.930 has the same limitation). Adjusting the model for the concentration in the
formulation would mean using a factor of 500.
The adjustment factor using formulation concentration is 500, which is calculated using
l,2-benzisothiazolin-3-one's maximum concentration (0.1%) and a value used in the screen level
model of 50%, which represents a group of active ingredients that are typically found in
agricultural food use products at concentrations >50%. Using the adjustment factor of 500 (50%
^- 0.1%) to account for the effect of the limitation of 0.1% of l,2-benzisothiazolin-3-one in
pesticide formulations on residue levels would certainly lower the model results even further that
what are presented in the Tables 4 and 5, below.
This dietary assessment includes the existing use of l,2-benzisothiazolin-3-one as a
pesticide inert ingredient used on growing crops under 40 CFR part 180.920. In addition, the
Agency has received a petition to establish an exemption from the requirement for a tolerance for
the use of l,2-benzisothiazolin-3-one as an inert ingredient in pesticides applied to animals under
40 CFR part 180.930 with the same limitations as currently exist under 180.920. This dietary
assessment also includes animals as a commodity. Therefore, the results of this assessment
cover all existing and currently proposed inert ingredient uses of l,2-benzisothiazolin-3-one.
Dietary exposures of concern from food are not likely from the use of l,2-benzisothiazolin-3-one
as inert ingredients in pesticide products.
13
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Table 4. Estimated Acute Dietary (Food) Risk Estimates for Inert Uses of BIT
Population Subgroup
U.S. Population (total)
All infants (< 1 year)
Children (1-2 years)
Children (3-5 years)
Children (6- 12 years)
Youth (13- 19 years)
Adults (20-49 years)
Adults (50+ years)
Females (13-49 years)
95th Percentile of Exposure
BIT Estimated
Exposure, mg/kg/day
0.0013 - 0.007
0.0028 - 0.014
0.0038 - 0.019
0.0027 - 0.014
0.0016 - 0.008
0.0010 - 0.005
0.00080 - 0.004
0.00076 - 0.004
0.00079 - 0.004
"/oaPAD17
8% - 40%
17o/0 . 84o/o
22% - 112%
16% - 82%
9% - 47%
6% - 29%
5% - 24%
5% - 23%
5% - 24%
I/ aPAD=0.017 mg/kg/day
TableS. Chronic Dietary (Food) Risk Estimates for Inert Uses of BIT
Population Subgroup
U.S. Population (total)
All infants (< 1 year)
Children (1-2 years)
Children (3-5 years)
Children (6- 12 years)
Youth (13- 19 years)
Adults (20-49 years)
BIT Estimated
Exposure, mg/kg/day
0.00048 - 0.0024
0.0010 - 0.0049
0.0017 - 0.0084
0.0012 - 0.0062
0.00070 - 0.0035
0.00040 - 0.0020
0.00035 - 0.0017
%cPAD2/
3% - 14%
6% - 29%
10% - 51%
7% - 37%
4% - 21%
2% - 12%
2% - 10%
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Population Subgroup
Adults (50+ years)
Females (13-49 years)
BIT Estimated
Exposure, mg/kg/day
0.00034 - 0.0017
0.00035 - 0.0017
%cPAD2/
2% - 10%
2% - 10%
21 cPAD=0.017 mg/kg/day
c. Dietary Risk from Drinking Water
Drinking water exposure to pesticides can occur through ground and surface water
contamination. In assessing drinking water risks, EPA considers acute (one day), chronic (long-
term) and, if applicable, cancer (overall) exposure, and uses either modeling or monitoring data,
if available, to estimate those risks. To determine the maximum contribution from water allowed
in the diet, EPA first looks at how much of the overall allowable risk is contributed by food and
then calculates a "drinking water level of comparison" (DWLOC) to determine whether modeled
or monitored exposure estimates exceed the allowable risk level. Estimated drinking water
concentrations (EDWCs) that are above the corresponding DWLOC exceed the Agency's level
of concern.
Based on environmental fate data, l,2-benzisothiazolin-3-one binds moderately with soil
and may potentially move with the soil during rainfall events and reach surface waters.
Although, l,2-benzisothiazolin-3-one has been shown to be hydrolytically stable with a half life
of > 30 days, it breaks down fairly quickly in aerobic soils. Outdoor use patterns of 1,2-
benzisothiazolin-3-one which may lead to contact with soil and/or surface water include: 1) the
application of agricultural pesticides that contain l,2-benzisothiazolin-3-one as an inert
ingredient, and 2) the application of paints that contain l,2-benzisothiazolin-3-one. Considering
l,2-benzisothiazolin-3-one's ready biodegradation and the small amount of (0.02 Ibs. per acre)
that may be applied to crops via the inert use and the small amount likely to come into contact
with soils/surface waters via the paint use, l,2-benzisothiazolin-3-one is not likely to be present
in drinking water sources at substantial concentrations. Therefore a quantitative drinking water
assessment was not conducted.
6. Residential Risk for Active Ingredient Uses
Residential exposure assessment considers all potential pesticide exposure, other than
exposure due to residues in food and drinking water. Exposure may occur during and after
application methods including painting via brush/roller and airless sprayer; handling BIT-
containing cleaning products through low-pressure spray, wiping, and mopping; and the washing
of clothing/textiles with BIT-containing laundry detergents. Each route of exposure (oral,
dermal, inhalation) is assessed, where appropriate, and risk is expressed as a Margin of Exposure
(MOE), which is the ratio of estimated exposure to an appropriate No Observed Effect Level
(NOAEL) does. Based on the application methods, BIT has been assessed for the residential
15
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mixing/loading/applicator (or "handler") exposure and for children's post-application exposure
that may occur from clothing/textile and via floor-cleaning products.
a. Toxicity
The toxicological endpoints and associated uncertainty factors used for assessing the non-
dietary risks for BIT are listed in Table 6.
A MOE greater than or equal to 100 is considered adequately protective for the
residential exposure assessment for the dermal, incidental oral and inhalation routes of exposure.
The MOE of 100 includes lOx for interspecies extrapolation, lOx for intraspecies variation.
Table 6. Toxicity Endpoints Selected for Assessing Occupational and Residential Risk for
BIT
Exposure
Scenario
Dose Used in Risk
Assessment
(mg/kg/day)
Target MOE, UF,
Special FQPA SF, for
Risk Assessment
Study and Toxicological Effects
Incidental Oral
(short and
intermediate
term
NOAEL= 5
mg/kg/day
MOE = 300 (lOx
interspecies
extrapolation, lOx
intraspecies variation)
FQPA SF= 1
DBUF=3
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.
and
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.
Dermal
All time periods
(occupational
and residential)
NOAEL= 5
mg/kg/day
MOE =100 (lOx
interspecies
extrapolation, lOx
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.
and
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.
-------
Exposure
Scenario
Inhalation
All time periods
(occupational
and residential)
Cancer
Dose Used in Risk
Assessment
(mg/kg/day)
NOAEL= 5
mg/kg/day
Target MOE, UF,
Special FQPA SF, for
Risk Assessment
MOE= 100
(lOx inter-species
extrapolation, lOxintra-
species variation)
An additional lOx
route-to-route
extrapolation is used to
determine if an
inhalation toxicity study
is warranted.
Study and Toxicological Effects
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.
and
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.
No cancer data available for l,2-benzisothiazolin-3-one
Notes: UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level,
LOAEL = lowest observed adverse effect level, DB UF = data base uncertainty factor, LOG = level of concern,
MOE = margin of exposure
b. Residential Handler Scenarios
i. Exposure Scenarios, Data and Assumptions
l,2-Benzisothiazolin-3-one may be added to residential-use products used to control
bacteria and fungi, including as a preservative for paint (e.g., EPA Reg. No. 72674-15) and
household cleaning products. The residential handler scenarios evaluated including handling
BIT-containing paint through brush/roller and airless spray application methods and handling
BIT-containing cleaning products through low-pressure spray, wiping, and mopping application
methods. Where the data were available, residential assessment assumed that the handlers would
be wearing short-pants and short-sleeved shirts
There are no chemical-specific exposure data to assess paint applications. Therefore,
dermal and inhalation exposures were assessed for brush and airless sprayer applications using
surrogate data. Specifically, PHED Version 1.1 values found in the Residential Exposure SOPs
(U.S. EPA, 1997a) were used (short pants, short-sleeved shirts). All homeowner painting
scenarios are believed to be best represented by the short-term exposure duration.
The following two scenarios were considered for residential handlers of BIT-containing
cleaning products:
Use of cleaner as a wipe on hard non-porous surfaces, and
Use of cleaner for mopping hard non-porous surfaces such as floors.
17
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These potential exposures from a general purpose cleaner are expected to be best
represented by the short-term duration. The short-term dermal and inhalation exposures were
assessed for wipe and mopping application methods using surrogate data. Specifically, values
from the Chemical Manufacturers Association (CMA) antimicrobial study (U.S. EPA, 1999)
were used. The dermal and inhalation exposures from these techniques have been normalized by
the amount of active ingredient handled and reported as unit exposures (UE) expressed as mg/lb
ai handled. In addition, product label maximum application rates, related use information, and
Agency standard values were used to assess residential handler exposures.
11.
Residential Handler Risk Estimates
Based on toxicological criteria and potential for exposure, the Agency has conducted
dermal and inhalation exposure assessments. A MOE greater than or equal to 100 is considered
adequately protective for the residential exposure assessment for the dermal, incidental oral and
inhalation routes of exposure. The MOE of 100 includes lOx for interspecies extrapolation, lOx
for intraspecies variation.
A summary of the residential handler exposures and risk are presented on Table 7. The
combined risks from dermal and inhalation exposures for all scenarios are below the Agency's
level of concern.
Table 7. Estimates of Short-term Exposures and Risks to Residential Handlers
Product
Paint
Cleaning
Scenario
Paint
brush/roller
Airless
sprayer
Wiping
Mopping
Absorbed
Dermal
Dosea
(mg/kg/day)
0.013
0.035
0.00055
0.00010
Inhalation
Dosea
(mg/kg/day)
4E-05
0.00089
3.2E-05
8.5E-06
Dermal
MOEb
(Target
MOE=
100)
370
140
9,000
48,000
Inhalation
MOEC
(Target
MOE = 100)
130,000
5,600
160,000
590,000
Total
MOEd
(Target
MOE =
100)
370
140
8,500
44,000
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c. Residential Post-Application Exposure
i. Exposure Scenarios, Data and Assumptions
Residential postapplication exposures result when bystanders (adults and children) come
in contact with BIT in areas where pesticide end-use products have recently been applied (e.g.,
treated hard surfaces/floors), or when children incidentally ingest the pesticide residues through
mouthing the treated end products/treated articles (i.e., hand-to-mouth or object-to-mouth
contact). The residential post-application scenarios considered in this assessment are exposure to
residues from hard surfaces (i.e., floors) that have been mopped with a product containing 1,2-
benzisothiazolin-3-one and the use of laundry detergents containing l,2-benzisothiazolin-3-one
where residues could remain on clothing articles after laundering.
There is the potential for dermal exposure to toddlers crawling on the floor. In addition to
dermal exposure, infants crawling on treated floors will also be exposed to 1,2-benzisothiazolin-
3-one via incidental oral exposure. To calculate incidental ingestion exposure to 1,2-
benzisothiazolin-3-one due to hand-to-mouth transfer, the scenarios established in EPA's
Standard Operating Procedures (SOPs) for Residential Exposure Assessments were used.
BIT labels also include a microbiocide use in laundry detergents, fabric softeners, and
stain removers (EPA Reg. No. 67071-23). To determine dermal and incidental oral exposure to
treated clothing, the guidance provided in the Human and Environmental Risk Assessment
(HERA) Guidance Document (2003) was used for indirect skin contact from wearing clothes and
oral exposure from mouthing or sucking on treated fabric.
ii. Residential Post-Application Risk Estimates
Based on toxicological criteria and potential for exposure, the Agency has conducted
dermal and incidental oral exposure assessments. A MOE greater than or equal to 100 is
considered adequately protective for the residential exposure assessment for the dermal,
incidental oral and inhalation routes of exposure. The MOE of 100 includes lOx for interspecies
extrapolation and lOx for intraspecies variation.
A summary of the residential handler exposures and risk are presented on Table 8. The
risks from dermal and incidental oral exposures for all scenarios are below the Agency's level of
concern.
19
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Table 8. Summary of Short- and Intermediate-Term Residential Postapplication
Exposures and Risks for BIT
Scenario
Dose
(mg/kg/day)
MOE
(Target MOE>100 for
dermal; >300 for oral)
Dermal Exposure
Treated Floors
Treated clothing
Residential
Setting
(Children)
Adults
Children
0.00055
0.00045
0.00070
9,200
11,000
7,200
Incidental Oral Exposure
Treated Floors
Treated clothing
Residential
Setting
(Children)
Children
0.00016 (ST)
7.7E-5 (IT)
0.003
3 1,000 (ST)
65,000 (IT)
1,700
7. Residential Risk for Inert Ingredient Uses
l,2-Benzisothiazolin-3-one is an inert ingredient in over 900 different products and is
used primarily as a materials preservative. The types of products that contain 1,2-
benzisothiazolin-3-one as an inert ingredient include turf insecticides, fungicides and herbicides;
garden and ornamental insecticides; flea and tick control products for pets; indoor crack and
crevice insecticides; paints; and household cleaners. Since l,2-benzisothiazolin-3-one is also
used as an active ingredient in paints and household cleaners at a higher percent formulation than
the inert, the inert exposure assessment did not include an analysis of the paint and cleaning
products. The residential exposure assessment addresses these exposures and shows that the
MOEs are above the Agency's level of concern. Furthermore, the inert assessment did not
specifically evaluate indoor crack and crevice uses since it was anticipated the applicator
exposures resulting from the outdoor lawn products (where l,2-benzisothiazolin-3-one is an inert
ingredient) would result in higher exposures based on the amount used per day. Additionally, it
was anticipated the post-application exposures resulting from the use of indoor residential
cleaners (where l,2-benzisothiazolin-3-one is an active ingredient) would result in higher
exposures when considering the fact that exposure to residues from a floor cleaner are much
more accessible than residues applied in cracks/crevices and along baseboards. An inert
exposure assessment was conducted for several representative residential products such as
various formulations of turf and garden products as well as, flea and tick pet spray products.
All of the input parameters used in this assessment are defaults provided in the Agency's
Residential SOPs (US EPA, 1997 and 2001). The percent formulation of 0.1% used in this
assessment was based on the tolerance exemption limitation as specified in 40 CFR 180.920 and
a review of several Confidential Statements of Formula (CSFs) for the various types of products.
-------
Tables 9-11 provide the input parameters and resulting exposures and MOEs for the inert uses.
Table 9. Applicator Short-term Exposures and MOEs for l,2-Benzisothiazolin-3-one used as an
Inert Ingredient in Aerosol Pet Flea and Tick Products
Exposure = UE x AR x N / BW
Unit Exposure (mg / Ib ai)
Application Rate (Ib ai/can)
Number of cans/day
Percent Absorption
Body weight (kg)
Daily Dose (mg/kg/day)
Oral NOAEL (mg/kg/day)
Target MOE
MOE
Total MOE
UE
AR
N
BW
Dermal
220
0.0004
0.5
41%
70
2.52E-04
5
100
20,000
19,000
Inhalation
2.4
0.0004
0.5
100%
70
6.70E-06
5
100
750,000
Table 10. Toddler Short-term Post-application Dermal Exposure and MOE for 1,2-
Benzisothiazolin-3-one used as an Inert Ingredient in Aerosol Pet Flea and Tick Products
Exposure = AR x T x SA x DA / BW
Application Rate (mg/cm2 of animal)
Transferable Fraction
Surface area of a child hug (cm2)
Dermal Absorption
Body weight (kg)
Daily Dose (mg/kg/day)
Oral NOAEL (mg/kg/day)
Target MOE
MOE
AR
T
SA
DA
BW
0.015
20%
1,875
41%
15
0.15
5
100
33
Table 11. Toddler Short-term Post-application Incidental Oral Exposure and MOE for 1,2-
Benzisothiazolin-3-one used as an Inert Ingredient in Aerosol Flea and Tick Pet Products
Exposure = AR x T x SA x SE x FQ / BW
Application Rate (mg/cm2 of animal)
Transferable Fraction
Surface area of a child's hand (cm2)
Saliva Extraction
Frequency (events/day)
Body weight (kg)
AR
T
SA
SE
FQ
BW
0.015
20%
20
50%
1
15
21
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Daily Dose (mg/kg/day)
Oral NOAEL (mg/kg/day)
Target MOE
MOE
0.0020
5
300
2,500
Because the dermal and oral toxicological effects are the same but the target MOEs
differ, it typically would be necessary to estimate an ARI for the total toddler exposure to the pet
product residues. However, since the dermal MOE is less than the target MOE of 100, it was not
necessary to estimate an ARI because it would result in a value less than 1. Therefore, the
dermal risk and resulting total risk (ARI) for toddlers exposed to l,2-benzisothiazolin-3-one
residues in pet products are of concern. It should be noted that these exposures are based on very
conservative models and default input parameters. The "transferable fraction" parameter is a
value that could be further refined with chemical specific data. However at this time, the percent
transfer factor from pet fur to skin is considered a data gap and is necessary to appropriately
refine this dermal exposure.
The results from the exposure and risk assessment for l,2-benzisothiazolin-3-one used as
an inert ingredient in other residential products (i.e., turf, garden, indoor crack and crevice, paint,
and cleaning products) show that all of the individual MOEs, total MOEs and ARIs are above the
Agency's level of concern.
8. Aggregate Risk
The Food Quality Protection Act amendments to the Federal Food, Drug, and Cosmetic
Act (FFDCA, Section 408(b)(2)(A)(ii)) require "that there is a reasonable certainty that no harm
will result from aggregate exposure to pesticide chemical residue, including all anticipated
dietary exposures and other exposures for which there are reliable information." Aggregate
exposure will typically include exposures from food, drinking water, residential uses of a
pesticide, and other non-occupational sources of exposure.
a. Acute and Chronic Aggregate Risks
The acute and chronic aggregate risk assessments generally include only dietary and
drinking water exposures. Drinking water exposure is not expected from any of the indoor or
outdoor uses of l,2-benzisothiazolin-3-one used as either an inert or active ingredient. Table 12
presents a summary of these exposures, as well as the aggregate risks. The acute and chronic
aggregate risk estimates associated with l,2-benzisothiazolin-3-one are below the Agency's level
of concern. It should be noted that the acute and chronic dietary exposures from the inert uses
were selected from the low range values as presented in Tables 14 and 15. It is reasonable to use
the low range values in the aggregate assessment given number of conservative assumptions that
were the basis for the inert dietary assessment.
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Table 12. Acute and Chronic Aggregate Dietary Exposures and Risks
Adults
Children
Adults %a or cPAD
Children %a or cPAD
(mg/kg/day)
Active
1.6E-03
3.7E-03
9.4%
21.1%
Inert
1.3E-03
3.8E-03
7.6%
22.4%
Aggregate
2.9E-03
7.5E-03
17.1%
44.1%
(mg/kg/day)
Active
1.6E-03
3.7E-03
9.4%
21.8%
Inert
4.8E-04
1.7E-03
2.8%
10.0%
Aggregate
2.1E-03
5.4E-03
12.2%
31.8%
b. Short- and Intermediate-Term Aggregate Exposures and Risks
Short- and intermediate-term aggregate exposures and risks were assessed for adults and
children that could be exposed to l,2-benzisothiazolin-3-one residues from the use of products in
non-occupational environments. This includes products that contain l,2-benzisothiazolin-3-one
as either the active or inert ingredient. The following list summarizes all of the potential sources
of l,2-benzisothiazolin-3-one exposures for adults and children:
Adult l,2-benzisothiazolin-3-one exposure sources:
Handling of paint containing BIT as an active or inert ingredient via brush
Handling of paint containing BIT as an active or inert ingredient via sprayer
Handling of cleaning products containing BIT as an active or inert ingredient during wiping
activities
Handling of cleaning products containing BIT as an active or inert ingredient during
mopping activities
Wearing BIT-treated clothing
Eating food having BIT residues from indirect food contact via the active ingredient paper
packaging use
Eating food having BIT residues from the inert ingredient pesticide use
Handling of EC, granular or RTU turf and garden products containing BIT as an inert
ingredient
Handling of pet flea control products containing BIT as an inert ingredient
Child l,2-benzisothiazolin-3-one exposures sources:
Post-application exposures to cleaning product residues containing BIT as an active or inert
ingredient used on hard surfaces (i.e., floors)
Wearing BIT-treated clothing
Eating food having BIT residues from indirect food contact via the active ingredient paper
packaging use
Eating food having BIT residues from the inert ingredient pesticide use
Post-application exposures to turf residues containing BIT as an active or inert ingredient
Post-application exposures to pet flea control product residues containing BIT as an inert
ingredient
The use patterns of the products and probability of co-occurrence must be considered
when selecting scenarios for incorporation in the aggregate assessment. In the case of 1,2-
23
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benzisothiazolin-3-one, homeowner painting activities occur only once or twice a year, while the
use of turf/garden and pet products occurs on an intermittent basis. Therefore the probability of
co-occurrence and the potential for exposure to residues from these products on the same day is
highly unlikely. However, it is likely that someone could clean the kitchen (mopping and wiping
activities) as well as, wear clothing treated with l,2-benzisothiazolin-3-one during the same day.
Table 13 summarizes the scenarios included in the short- and intermediate-term aggregate
assessments.
Table 13. Exposure Scenarios Included in the Aggregate Assessments
Short-term Aggregate
Intermediate-Term Aggregate
Adults
chronic dietary - inert
chronic dietary - active
handling cleaning products -
wiping
handling cleaning products -
mopping
treated clothing
chronic dietary - inert
chronic dietary - active
treated clothing
Children
chronic dietary - inert
chronic dietary - active
post-app to cleaning product
mopping
treated clothing
chronic dietary - inert
chronic dietary - active
post-app to cleaning product - mopping
treated clothing
The chronic dietary exposures were used in both the short- and intermediate-term
aggregate assessment because chronic dietary exposures occur nearly every day (as opposed to
acute dietary exposures occurring on a one-time basis). Therefore, short- or intermediate-term
non-dietary exposures have a much higher probability to concur with the chronic dietary intake
rather than the acute dietary intake.
Cleaning activities in a residential setting occur on a short-term basis. However, the BIT-
containing cleaning products are also labeled for use in institutional settings such as day care
facilities where cleaning activities can occur on an intermediate-term basis. Therefore, children
could have exposure to cleaning product residues on a more continuous basis in a day care
facility thus, these post-application scenarios were included in the intermediate-term aggregate
assessment.
Since the toxicity endpoints for all of the routes of exposure (oral, dermal and inhalation)
are based on the same study and same toxic effect, all routes are aggregated together. However,
the aggregate risk index (ARI) method outlined in OPP guidance for aggregate risk assessment
(September 1, 2000, Standard Operating Procedure (SOP) for Incorporating Screening Level
Estimates of Drinking Water Exposure into Aggregate Risk Assessments) was utilized in the
assessment. This method was used because the oral, dermal and inhalation endpoints have
different uncertainty factors that need to be applied. A risk index 1 indicates a risk of no
concern. The short-term ARIs for adults and children were 6.8 and 1.9, respectively, while the
intermediate-term ARIs for adults and children were 7.5 and 1.9, respectively. Therefore short-
term and intermediate-term aggregate risks are below the Agency's level of concern.
-------
Tables 14 and 15 present the resulting ARIs for the short- and intermediate term aggregate assessments, respectively.
Table 14. Short-term Aggregate Risks
Exposure Routes
Adults
Oral Ingestion MOEs
Inhalation MOEs
Dermal MOEs
Total MOE
Toddlers
Oral Ingestion MOEs
Inhalation MOEs
Dermal MOEs
ARI
Dietary
Active
3,100
NA
NA
1,400
NA
NA
Inert
10,000
NA
NA
2,900
NA
NA
Total
2,400
NA
NA
930
NA
NA
Clothing
Post-App
NA
NA
11,000
1,700
NA
7,100
5.2
Hard Surface Cleaning
Applicator
Wipe
NA
160,000
9,100
8,600
NA
NA
NA
Mop
NA
590,00
50,000
46,000
NA
NA
NA
Post-App
NA
NA
NA
NA
31,000
NA
9,100
48.5
Total ARI
NA
120,000
7,700
7,200
31,000
NA
9,100
48.5
6.8
1.9
25
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Table 15. Intermediate-term Aggregate Risks
Exposure Routes
Adults
Oral Ingestion
Inhalation MOEs
Dermal MOEs
Toddlers
Oral Ingestion
Inhafetion MOEs
Dermal MOEs
ARI
Dietary
Active
3,100
NA
NA
1,400
NA
NA
Inert
10,000
NA
NA
2,900
NA
NA
Total
2,400
NA
NA
930
NA
NA
Clothing
Post-App
NA
NA
11,000
1,700
NA
7,100
5.2
Hard Surface
PdlMflp
Mop
NA
NA
NA
31,000
NA
9,100
48.5
ARI
7.5
1.9
9. Occupational Risk
Workers can be exposed to a pesticide through mixing, loading, and/or applying a
pesticide, or re-entering treated sites. Occupational handlers of BIT include formulated product
handlers, material preservative handlers, and metal working fluids handlers. Occupational risk
for all of these potentially exposed populations is measured by a Margin of Exposure (MOE)
which determines how close the occupational exposure comes to a No Observed Adverse Effect
Level (NOAEL) from toxicological studies. In the case of BIT, MOEs greater than 100 are not
of concern to the Agency. This MOE includes the standard safety factors of 10X for intraspecies
variability (i.e., differences among humans) and 10X for interspecies variability (differences
between humans and animals).
Occupational risk is assessed for exposure at the time of application (termed "handler"
exposure) and is assessed for exposure following application, or post-application exposure.
Application parameters are generally defined by the physical nature of the formulation (e.g.,
formula and packaging), by the equipment required to deliver the chemical to the use site, and by
the application rate required to achieve an efficacious dose.
For more information on the assumptions and calculations of potential risk of BIT to
workers, see the Occupational Exposure Assessment section in the "Human Health Risk
Assessment (Revised)," dated July 11, 2005.
a. Occupational Toxicity
Please see Table 4 as it provides a listing of the toxicological endpoints used in the
occupational risk assessment for BIT.
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b. Occupational Handler Exposure
Formulated Product Handlers:
EPA has assessed the exposure to handlers mixing/loading/applying products containing
the active ingredient. The following handler exposure scenarios which involve handling the
formulated product were assessed for l,2-benzisothiazolin-3-one to represent the high end of
industrial uses of the formulated product.
Pouring the BIT-containing liquid biocide preservative into industrial process
intermediate materials (dispersions, slurries, emulsions, solutions, etc.)
Pouring the BIT-containing liquid biocide preservative into industrial process water for
leather and photo processing systems
Pouring the BIT-containing liquid biocide preservative into metalworking fluid
Pouring the BIT-containing liquid biocide preservative during oil field activities
There are no chemical-specific exposure data to assess primary handler applications.
Therefore, dermal and inhalation exposures were assessed using CMA surrogate exposure data.
Specifically, the liquid pour for preservative data from CMA were used as surrogate data for the
scenarios involving the pouring of liquid preservatives into industrial process intermediate
materials, leather and photo processing systems, and oil fields; the liquid pour for metal working
fluid data from CMA were used as surrogate data for the liquid pouring of preservatives into
metalworking fluid; the liquid pump for preservative data from CMA were used as surrogate data
for the liquid pumping of preservatives into oil fields. In addition, product label maximum
application rates, related use information, and Agency standard values were used to assess
exposures.
Material Preservative Handlers:
EPA has assessed the exposure to handlers mixing/loading/applying products containing
the active ingredient as a material preservative, not the formulated product (previously defined as
"secondary" handlers). This includes those individuals exposed to the active ingredient as a
direct result of its incorporation into an end use product (e.g., individuals using caulk or paint
that in itself is not a registered product). The scenarios assessed have been selected to represent
the high end of exposure to these types of products such as application of stains, water-based
adhesives, caulks, sealants, grouts, spackling, ready-mixed cements, and ready-mixed wallboard
compounds. Based on end-use product application methods, it is assumed that exposures while
applying paints will be equal to or greater than exposures while applying building materials.
(Note: metal working fluids for machinists are assessed separately below.) The following
material uses were assessed to represent the high end of exposure to l,2-benzisothiazolin-3-one:
Handling BIT-containing paint through brush/roller and airless sprayer application
methods.
Handling BIT-containing cleaning products through wiping and mopping application
methods.
27
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These handler exposure scenarios were assessed using surrogate unit exposure data from
PHED Version 1.1 for the painting scenarios and using surrogate unit exposure from CMA for
the cleaning product scenarios. For the painting scenarios, it was assumed that commercial
painters apply 5 gallons (50 Ibs) of paint through brush/roller application methods and 50 gallons
(500 Ibs) of paint through airless sprayer application methods. For the cleaning product
scenarios, it was assumed that occupational handlers (i.e., janitors) use 1 liter for wiping and 2
gallons for mopping.
Metal Working Fluids Handlers:
The potential inhalation and dermal exposure may exist when using treated metal
working fluid. A screening-level long-term inhalation exposure estimate for treated metal
working fluids has been developed using the OSHA PEL for oil mist. The Agency conducted
the screening level assessment for metal working fluids using the USEPA/OPPTS Chemical
Engineering Branch (CEB) model (U.S. EPA, 1991). The CEB model uses measured and/or
assumed airborne oil mist concentrations for metal working operations. Since no measured
concentrations are available for l,2-benzisothiazolin-3-one, the high-end oil mist concentration is
based on the OSHA's Permissible Exposure Limit (PEL) of 5 mg/m3 (NIOSH, 1998). EPA Reg.
No. 72674-15 indicates that 0.25% (i.e., 0.0025) of the label product is added to metal working
fluids and of that, only 19.3% is the active ingredient (l,2-benzisothiazolin-3-one). Therefore,
the upper bound air concentration of l,2-benzisothiazolin-3-one that a worker is exposed to is 5
mg/m3 x 0.0025 x 0.09 or an air concentration of 0.0011 mg/m3. Additionally, the following
assumptions were made in the assessment: the inhalation rate for adults is 1.25 m3/hr; the
exposure duration is 8 hours; and body weight is 70 kg.
A screening-level long-term dermal exposure estimate was derived from the 2-Hand
Dermal Immersion in Liquid Model in ChemSTEER (EPA/OPPT). The weight fraction of 1,2-
benzisothiazolin-3-one in metal working fluids is 0.00048 (0.0025 formulated product added to
oil x 0.193 ai in formulated product = 0.00048), calculated from EPA Reg. No. 72674-15. Based
on the model for emersion of hands in metal working fluids, the long-term absorbed dermal dose
is estimated at 0.025 mg/kg/day.
c. Occupational Handler Risk Summary
The results of the MOE analysis are presented in Table 16. The calculated short- and
intermediate-term dermal MOEs are greater than the target MOEs, and therefore, are not of
concern with the exception of the dermal MOE for commercial painting with an airless sprayer
which is 90. However, it is believed that the paint matrix has the potential to reduce the dermal
exposure. Moreover, the dermal absorption factor of 41 percent was not adjusted to account for
the potential reduction of the bioavailability of BIT in paint because of a lack of chemical-
specific data. Therefore, the dermal MOE of 90 for the airless sprayer may be an overestimate of
risk. In addition, the total MOEs (inhalation + dermal) have been presented. The total MOEs are
all greater than 100, indicating no risks of concern, except for the commercial painting with an
airless sprayer where the total MOE = 85. As mentioned above, the Agency believes that actual
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dermal exposures resulting from this scenario are likely to result in risks that do not exceed the
Agency's level of concern.
Table 16. Estimates of Short- and Intermediate-term Risks to Occupational Handlers of
l,2-Benzisothiazolin-3-one
Scenarios
Use Site Category
Inhalation MOEb
(Target MOE =100)
Dermal MOEC
(Target MOE =100)
Total MOE
(Target =
100)
Occupational/Industrial Handler (Formulated Products)
Mixing/loading/applying BIT-containing
biocides using liquid open pour
methods for preservation of industrial
process intermediate materials.
(Gloves)
Mixing/loading/applying BIT-containing
biocides using liquid open pour
methods for industrial process and
water system use. (Gloves)
Mixing/loading/applying BIT-containing
biocides using liquid open pour
methods for preservation of
metalworking fluids (Gloves)
Mixing/loading/applying BIT-containing
biocides using liquid open pour
methods for preservative products
(Gloves)
Mixing/loading/applying BIT-containing
biocides using liquid pump methods for
preservative products (Gloves)
Material
Preservatives
Industrial Processes
and Water Systems
Material
Preservatives
Oil/gas Drilling
fluids
Oil Secondary
Recovery
20,000
25,000
51,000
7E+06
830
1,300
1,600
5,700
4.5E+05
130
1,200
1,500
5,100
4.2E+05
110
Occupational Material Preservative Handlers (In-can Preservatives)
Handling BIT-containing cleaning
solutions through wiping application
methods (No gloves)
Handling BIT-containing cleaning
solutions through mopping application
methods (No gloves)
Handling BIT-containing paint through
paint brush/roller
application methods (No gloves)
Handling BIT-containing paint through
airless sprayer
application methods (No gloves)
Material
Preservatives
Material
Preservatives
Material
Preservatives
Material
Preservatives
79,000
290,000
50,000
1,700
4,500
24,000
190
90
4,300
22,000
190
85
d. Occupational Post-Application Exposure
Postapplication exposures may occur in industrial settings around the water systems via
inhalation, and dermal exposures may occur while maintaining industrial equipment. However,
occupational post-application dermal and inhalation exposures to l,2-benzisothiazolin-3-one are
29
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likely to be minimal when compared to handler exposure because of dilution during processing
or when compared to machinists using the metal working fluid. No postapplication exposure
data have been submitted to the agency to determine the extent of postapplication exposures in
the industrial settings. Inhalation exposures are expected to be minimal because aerosol
generation is not expected and the vapor pressure of l,2-benzisothiazolin-3-one is low.
B. Environmental Risk Assessment
A summary of the Agency's environmental risk assessment is presented below. The
following risk characterization is intended to describe the magnitude of the estimated
environmental risks for BIT use sites and any associated uncertainties.
For detailed discussions of all aspects of the environmental risk assessment, see the
document "Environmental Risk Assessment and Characterization - l,2-Benzisothiazolin-3-one
(BIT)", dated July 7, 2005.
1. Environmental Fate and Transport
The environmental fate assessment for l,2-benzisothiazolin-3-one was based on limited
information; data were only available for hydrolysis, aerobic soil metabolism, and
adsorption/desorption. These data indicate that l,2-benzisothiazolin-3-one is hydrolytically
stable (half-life > 30 days), but breaks down fairly quickly in aerobic soils (half-life < 24 hours
in sandy loam soil). l,2-Benzisothiazolin-3-one shows moderate to strong binding to soils, with
adsorption Kd values estimated to be between 1.24 and 9.56. If used outdoors, 1,2-
benzisothiazolin-3-one may possibly move with soil during rainfall events and potentially reach
surface waters. However, it breaks down aerobically on the surface soils. Since it has a
moderate binding potential to soils, it is not likely to migrate into the ground and there is low
potential for ground water contamination. Furthermore, with a Kow value of 20 at 25 ° C, 1,2-
benzisothiazolin-3-one is unlikely to bioaccumulate in aquatic organisms.
2. Ecological Risk
The available ecological effects data for l,2-benzisothiazolin-3-one are somewhat
limited. Based on acute toxicity information, l,2-benzisothiazolin-3-one displays low to
moderate toxicity to birds and mammals. It is moderately toxic to freshwater fish and
invertebrates, slightly toxic to marine/estuarine fish, and highly toxic to marine/estuarine
invertebrates. A submitted rat developmental study provided a NOAEL of 40 mg/kg/day. There
was no aquatic organism chronic toxicity information available for l,2-benzisothiazolin-3-one.
Phytotoxicity data are limited, with one algae acute study found in published scientific literature,
which indicates that l,2-benzisothiazolin-3-one is highly toxic to green algae. Acute oral
toxicity data for l,2-benzisothiazolin-3-one are shown in Table 17, acute ecotoxicity data are
shown in Table 18, and other ecotoxicity data (subacute dietary, dermal, and developmental) are
shown in Table 19.
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Table 17. Acute Oral Toxicity of l,2-Benzisothiazolin-3-one
Species
LD50/LC50
(mg/kg)
NOAEL/NOAEC
Toxicity Category
Bird
Bobwhite quail
(Colinus virginianus)
453
NA
Moderately toxic
Mammal
Rat
650 - males
784 - females
Table 18. Acute Ecotoxicity of l,2-Benzisothiazolin-3-one
Species
LD50/LC50
(mg/kg)
NOAEL/NOAEC
Toxicity Category
Freshwater Fish
Rainbow Trout
(Oncorhynchus mykiss)
Rainbow Trout
(Oncorhynchus mykiss)
1.3
1.6
0.74
Moderately toxic
Moderately toxic
Freshwater Invertebrate
Waterflea
(Daphnia magna)
Waterflea
(Daphnia magna)
1.5
o o
J.J
0.7
1.4
Moderately toxic
Moderately toxic
Estuarine/Marine Fish
Sheep shead minnow
(Cyprinodon variegatus)
12.2
3.3
Slightly toxic
Estuarine/Marine Invertebrates
Mysid shrimp
(Mysidopsis bahia)
Pacific oyster
(Crassostrea gigas)
0.99
0.047
0.25
0.024
Highly toxic
Very highly toxic
Aquatic Algae
Green algae, species not
indicated
0.1 5 (72-hour
EC50)
31
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Table 19. Other Toxicity Studies of l,2-Benzisothiazolin-3-one
Species
LD50/LC50
(mg/kg)
NOAEL/
NOAEC
LOAEL/
LOAEL
Toxicity Category
Subacute Dietary Toxicity of l,2-Benzisothiazolin-3-one to Birds
Bobwhite quail
(Colinus virginianus)
>5620
Practically non-toxic
Acute Dermal Toxicity of l,2-Benzisothiazolin-3-one to Rats
Rats
>2000
Developmental Toxicity of l,2-Benzisothiazolin-3-one to Rats
Rats
40
100
The indoor uses of BIT considered in this RED make it unlikely that any appreciable
exposure to terrestrial or aquatic organisms would occur. Facilities using BIT for indoor
industrial applications are required to have NPDES permits before discharging effluents into
receiving waters. The potential exposure to terrestrial and aquatic species from the oil recovery
uses of BIT cannot be estimated at this time, as there is currently no validated model available
for such a purpose.
l,2-Benzisothiazolin-3-one is used as an inert ingredient in pesticide products but the
allowable amount that can be applied is small (not more than 0.1% formulation and 0.02 Ibs. per
acre). Data indicate that l,2-benzisothiazolin-3-one breaks down quickly in aerobic soils (half-
life < 24 hours in sandy loam soil). l,2-Benzisothiazolin-3-one's ready biodegradation in soil
and small application amount greatly reduce the exposure potential for terrestrial and aquatic
organisms. Run-off into surface water from pesticidal uses is likely to be low and it is not likely
to be present in water sources at substantial concentrations. Therefore, risk to non-target
organisms is not anticipated from the use of l,2-benzisothiazolin-3-one.
3. Listed Species Consideration
Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all
federal agencies to consult with the National Marine Fisheries Service (NMFS) for marine and
anadromous listed species, or the United States Fish and Wildlife Services (FWS) for listed
wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species
or their designated habitat. Each federal agency is required under the Act to insure that any
action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a
listed species or result in the destruction or adverse modification of designated critical habitat.
To jeopardize the continued existence of a listed species means "to engage in an action that
reasonably would be expected, directly or indirectly, to reduce appreciably the likelihood of both
the survival and recovery of a listed species in the wild by reducing the reproduction, numbers,
or distribution of the species." 50 C.F.R. 402.02.
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To facilitate compliance with the requirements of the Endangered Species Act subsection
(a)(2) the Environmental Protection Agency, Office of Pesticide Programs has established
procedures to evaluate whether a proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed species in the wild by
reducing the reproduction, numbers, or distribution of any listed species (U.S. EPA 2004). After
the Agency s screening-level risk assessment is performed, if any of the Agency s Listed Species
LOG Criteria are exceeded for either direct or indirect effects, a determination is made to identify
if any listed or candidate species may co-occur in the area of the proposed pesticide use. If
determined that listed or candidate species may be present in the proposed use areas, further
biological assessment is undertaken. The extent to which listed species may be at risk then
determines the need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.
For certain use categories, the Agency assumes there will be minimal environmental
exposure, and only a minimal toxicity data set is required (Overview of the Ecological Risk
Assessment Process in the Office of Pesticide Programs U.S. Environmental Protection Agency -
Endangered and Threatened Species Effects Determinations, 1/23/04, Appendix A, Section IIB,
pg.81). Chemicals in these categories therefore do not undergo a full screening-level risk
assessment, and are considered to fall under a no effect determination. The active ingredient
uses of l,2-benzisothiazolin-3-one fall into this category.
The inert uses of l,2-benzisothiazolin-3-one are also considered to fall under a "no effect"
determination, for the following reasons:
The allowable amount that can be applied is small (not more than 0.1% formulation and
0.02 Ibs. per acre).
Data indicate that l,2-benzisothiazolin-3-one breaks down quickly in aerobic soils (half-
life < 24 hours in sandy loam soil).
l,2-Benzisothiazolin-3-one s ready biodegradation in soil and small application result in
minimal to no terrestrial or aquatic organism exposure.
33
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IV. Risk Management, Reregistration, and Tolerance Reassessment Decision
A. Determination of Reregistration Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether or not products containing the active
ingredient are eligible for reregistration. The Agency has previously identified and required the
submission of the generic (i.e., active ingredient-specific) data required to support reregistration
of products containing BIT as an active ingredient. The Agency has completed its review of
these generic data, and has determined that the data are sufficient to support reregistration of all
supported products containing BIT.
The Agency has completed its assessment of the dietary, occupational, drinking water,
and ecological risks associated with the use of pesticide products containing the active ingredient
BIT. The Agency has determined that BIT containing products are eligible for reregistration
provided that: (i) current data gaps and confirmatory data needs are addressed; (ii) the risk
mitigation measures outlined in this document are adopted; and (iii) label amendments are made
to reflect these measures where necessary. Appendix A summarizes the uses of BIT that are
eligible for reregistration. Appendix B identifies the generic data requirements that the Agency
reviewed as part of its determination of reregistration eligibility of BIT and lists the submitted
studies that the Agency found acceptable. Data gaps are identified as generic data requirements
that have not been satisfied with acceptable data.
Based on its evaluation of BIT, the Agency has determined that BIT products, unless
formulated and used as specified in this document, would present risks inconsistent with FIFRA.
Accordingly, should a registrant fail to implement any of the risk mitigation measures identified
in this document, the Agency may take regulatory action to address the risk concerns from the
use of BIT. If all changes outlined in this document are incorporated into the product
formulations, then all current risks for BIT will be substantially mitigated for the purposes of this
determination.
B. Public Comments and Responses
Through the Agency's public participation process, EPA worked with stakeholders and
the public to reach the regulatory decisions for BIT. During the public comment period on the
risk assessments, which closed on September 19, 2005, the Agency received comments from
Acti-Chem Specialties, Inc.; Arch Chemicals, Inc., Clariant Corporation; International Specialty
Products, Rohm & Haas Company, and Troy Corporation in response to EPA's draft risk
assessment (RA) for BIT. The comments submitted by these registrants include areas of
toxicology, exposure, and risks. The Agency's responses to these comments are incorporated
into the risk assessment and revised chapters, which are available in the public docket at
www.epa.gov/edocket. docket # OPP-2005-0200.
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C. Regulatory Position
1. Food Quality Protection Act Findings
a. "Risk Cup" Determination
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated
with BIT. The Agency has concluded that the tolerance exemption for the use of BIT as an inert
ingredient meets the FQPA safety standards and that the risk from dietary (food sources only)
exposure is within the "risk cup." An aggregate assessment was conducted for exposures
through food and residential exposure. The Agency has determined that the human health risks
from these combined exposures are within acceptable levels. In reaching this determination,
EPA has considered the available information on the special sensitivity of infants and children,
as well as aggregate exposure from food and water.
b. Determination of Safety to U.S. Population
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated
with BIT. The Agency has determined that the established tolerance exemption for BIT meets
the safety standards under the FQPA amendments to section 408(b)(2)(D) of the FFDCA, and
that there is a reasonable certainty no harm will result to the general population or any subgroup
from the use of BIT. In reaching this conclusion, the Agency has considered all available
information on the toxicity, use practices and exposure scenarios, and the environmental
behavior of BIT.
The acute and chronic aggregate risk assessments generally include only dietary and
drinking water exposures. Since drinking water exposure is not expected from any of the indoor
or outdoor uses of l,2-benzisothiazolin-3-one used as either an inert or active ingredient, the
acute and chronic aggregate assessments only included dietary exposures from the active indirect
food uses (i.e., use in food-contact packaging) and inert dietary exposures from agricultural
pesticide uses. The acute and chronic aggregate risk estimates associated with 1,2-
benzisothiazolin-3-one are well below the Agency's level of concern.
The short- and intermediate-term aggregate assessments were conducted for adults and
children. Since the toxicity endpoints for all of the routes of exposure (oral, dermal and
inhalation) are based on the same study and same toxic effect, all routes are aggregated together.
The aggregate risk index (ARI) method was utilized in the assessment. Short- and intermediate-
term aggregate calculated risks are below the Agency's level of concern.
c. Determination of Safety to Infants and Children
EPA has determined that the established tolerance exemption for l,2-benzisothiazolin-3-
one, with amendments and changes as specified in this document, meet the safety standards
under the FQPA amendments to section 408(b)(2)(C) of the FFDCA, that there is a reasonable
certainty of no harm for infants and children. The safety determination for infants and children
considers factors of the toxicity, use practices, and environmental behavior noted above for the
general population, but also takes into account the possibility of increased dietary exposure due
35
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to the specific consumption patterns of infants and children, as well as the possibility of
increased susceptibility to the toxic effects of BIT residues in this population subgroup.
No Special FQPA Safety Factor is necessary to protect the safety of infants and children.
In determining whether or not infants and children are particularly susceptible to toxic effects
from BIT residues, the Agency considered the completeness of the database for developmental
and reproductive effects, the nature of the effects observed, and other information. The FQPA
Safety Factor has been removed (i.e., reduced to IX) for BIT based on: (1) the lack of evidence
of increased susceptibility in the 2-generation reproduction toxicity study and the available
developmental toxicity data; and (2) the risk assessment does not underestimate the potential risk
for infants and children.
d. Cumulative Risks
Risks summarized in this document are those that result only from the use of 1,2-
benzisothiazolin-3-one. The Food Quality Protection Act (FQPA) requires that the Agency
consider "available information" concerning the cumulative effects of a particular pesticide's
residues and "other substances that have a common mechanism of toxicity." The reason for
consideration of other substances is due to the possibility that low-level exposures to multiple
chemical substances that cause a common toxic effect by a common toxic mechanism could lead
to the same adverse health effect as would a higher level of exposure to any of the substances
individually. 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 for l,2-benzisothiazolin-3-one. For information regarding EPA's efforts to determine
which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of
such chemicals, see the policy statements released by EPA's Office of Pesticide Programs
concerning common mechanism determinations and procedures for cumulating effects from
substances found to have a common mechanism on EPA's website at
http ://www. epa. gov/pesticides/cumulative/.
e. Endocrine Disrupter Effects
EPA is required under the FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances (including all pesticides and inerts) "may have
an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or
such other endocrine effect as the Administrator may designate." Following the
recommendations of its Endocrine Disrupter Screening and Testing Advisory Committee
(EDSTAC), EPA determined that there was a scientific basis for including, as part of the
program, the androgen and thyroid hormone systems, in addition to the estrogen hormone
system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of
potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an effect in humans,
FFDCA authority to require the wildlife evaluations. As the science develops and resources
allow, screening of additional hormone systems may be added to the Endocrine Disrupter
Screening Program (EDSP).
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When the appropriate screening and/or testing protocols being considered under the
Agency's EDSP have been developed, l,2-benzisothiazolin-3-one may be subjected to additional
screening and/or testing to better characterize effects related to endocrine disruption.
2. Tolerance Summary
No pesticide tolerances have been established for BIT. 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 exemption is for use on growing crops
under 40 CFR part 180.920 and is considered reassessed. In addition, the Agency has received a
petition to establish an exemption from the requirement for a tolerance for the use of 1,2-
benzisothiazolin-3-one as an inert ingredient in pesticides applied to animals under 40 CFR part
180.930. The risk assessments in this document took into consideration animals as a commodity.
Therefore, the results of this assessment cover all existing and currently proposed inert ingredient
uses of l,2-benzisothiazolin-3-one. Dietary exposures of concern from food are not likely from
the use of l,2-benzisothiazolin-3-one as inert ingredients in pesticide products.
The existing exemption from the requirement of a tolerance, as well as the proposed
exemption, are summarized in Table 20.
a. Tolerances Currently or Proposed To Be Listed Under 40 CFR
§180.920
Table 20. Tolerance Reassessment Summary for BIT
Tolerance Exemption
Expression
1 ,2-benzisothiazolin-3 -one
(Also known as "BIT")
CAS
Number
2634-33-5
40 CFR §
180.9201
180.9302
Current Limits
Not more than
0.1% of
formulation. Not
more than 0.02
Ibs. to be applied
per acre.
Reassessed
Limits
Not more than
0.1% of
formulation. Not
more than 0.02
Ibs. to be applied
per acre.
Use
preservative/
stabilizer
1. Residues listed in 40 CFR §180.920 are exempted from the requirement of a tolerance when used as inert
ingredients in pesticide formulations when applied to growing crops only.
2. Residues listed in 40 CFR § 180.930 are exempted from the requirement of a tolerance when used as inert
ingredients in pesticide formulations when applied to animals only (pending).
b. Codex Harmonization
Currently there are no Codex MRLs established for BIT.
37
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D. Regulatory Rationale
The Agency has determined that BIT is eligible for reregistration provided that additional
required data confirm this decision and that the risk mitigation measures outlined in this
document are adopted, and label amendments are made to reflect these measures.
The following is a summary of the rationale for managing risks associated with the use of
BIT. Where labeling revisions are warranted, specific language is set forth in the summary
tables of Section V of this document.
1. Human Health Risk Management
a. Dietary (Food) Risk Mitigation
The acute and chronic dietary exposure estimates for the active ingredient uses are below
the Agency's level of concern. While the acute risk estimates for the inert uses exceed 100% of
the aPAD for children, considering the unrefined and conservative nature of this screening level
model (e.g., inclusion of all commodities; 100% of commodities are treated; adjustment factor
for application rate), the results for all population subgroups are considered not to be of concern.
Therefore, no risk mitigation measures are required to address exposure to BIT residues in food.
b. Drinking Water Risk Mitigation
Considering l,2-benzisothiazolin-3-one's ready biodegradation and the small amount of
(0.02 Ibs. per acre) that may be applied to crops via the inert use and the small amount likely to
come into contact with soils/surface waters via the paint use, l,2-benzisothiazolin-3-one is not
likely to be present in drinking water sources at substantial concentrations. Therefore a
quantitative drinking water assessment was not conducted and no risk mitigation measures are
required.
c. Residential Risk Mitigation
Residential risk estimates for the uses of BIT as an active ingredient are below the
Agency's level of concern. Therefore, no risk mitigation measures are required to address
exposure to BIT from these uses. However, residential risk estimates regarding the use of 1,2-
benzisothiazolin-3-one as an inert ingredient in pet flea and tick products exceed the Agency's
level of concern for children.
In evaluating the inert uses in pet products, the percent formulation of 0.1% was used in
the assessment based on the tolerance exemption limitation as specified in 40 CFR 180.920 and a
review of the formulations of various products. The Agency has determined that in a percent
formulation of 0.033% BIT would result in the target MOE of 100 for the scenario of toddler
post-application dermal exposure, which will adequately address the Agency's risk concerns.
All pet products containing BIT as an inert ingredient must contain a maximum of 0.033% BIT
in order to be eligible for reregistration.
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d. Occupational Risk Mitigation
i. Handler Exposure
The calculated short- and intermediate-term dermal MOEs are greater than the target
MOEs, and therefore, are not of concern with the exception of the dermal MOE for commercial
painting with an airless sprayer which is 90. However, it is believed that the paint matrix has the
potential to reduce the dermal exposure. Moreover, the dermal absorption factor of 41 percent
was not adjusted to account for the potential reduction of the bioavailability of BIT in paint
because of a lack of chemical-specific data. Therefore, the dermal MOE of 90 for the airless
sprayer may be an overestimate of risk. In addition, the total MOEs (inhalation + dermal) have
been presented. The total MOEs are all greater than 100, indicating no risks of concern, except
for the commercial painting with an airless sprayer where the total MOE = 85. As mentioned
above, the Agency believes that actual dermal exposures resulting from this scenario are likely to
result in risks that do not exceed the Agency's level of concern.
ii. Post-Application Risk Mitigation
Postapplication exposures may occur in industrial settings around the water systems via
inhalation, and dermal exposures may occur while maintaining industrial equipment. However,
occupational postapplication dermal and inhalation exposures to l,2-benzisothiazolin-3-one are
likely to be minimal when compared to handler exposure because of dilution during processing
or when compared to machinists using the metal working fluid. Inhalation exposures are
expected to be minimal because aerosol generation is not expected and the vapor pressure of 1,2-
benzisothiazolin-3-one is low, therefore no risk mitigation measures are required.
2. Environmental Risk Management
The indoor uses of BIT make it unlikely that any appreciable exposure to terrestrial or
aquatic organisms would occur. Facilities using BIT for indoor industrial applications are
required to have NPDES permits before discharging effluents into receiving waters. Therefore,
no risk mitigation measures are required
When used as an inert ingredient in pesticide products the allowable amount that can be
applied is small (not more than 0.1% formulation and 0.02 Ibs. per acre). Data indicate that 1,2-
benzisothiazolin-3-one breaks down quickly in aerobic soils (half-life < 24 hours in sandy loam
soil). l,2-Benzisothiazolin-3-one's ready biodegradation in soil and small application amount
greatly reduce the exposure potential for terrestrial and aquatic organisms. Run-off into surface
water from pesticidal uses is likely to be low and it is not likely to be present in water sources at
substantial concentrations. Therefore, no risk mitigation measures are required.
3. Listed Species Considerations
a. The Endangered Species Program
Section 7 of the Endangered Species Act, 16 U.S.C. Section 1536(a)(2), requires all
federal agencies to consult with the National Marine Fisheries Service (NMFS) for marine and
anadromous listed species, or the United States Fish and Wildlife Services (FWS) for listed
39
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wildlife and freshwater organisms, if they are proposing an "action" that may affect listed species
or their designated habitat. Each federal agency is required under the Act to insure that any
action they authorize, fund, or carry out is not likely to jeopardize the continued existence of a
listed species or result in the destruction or adverse modification of designated critical habitat.
To jeopardize the continued existence of a listed species means "to engage in an action that
reasonably would be expected, directly or indirectly, to reduce appreciably the likelihood of both
the survival and recovery of a listed species in the wild by reducing the reproduction, numbers,
or distribution of the species." 50 C.F.R. 402.02.
To facilitate compliance with the requirements of the Endangered Species Act subsection
(a)(2) the Environmental Protection Agency, Office of Pesticide Programs has established
procedures to evaluate whether a proposed registration action may directly or indirectly reduce
appreciably the likelihood of both the survival and recovery of a listed species in the wild by
reducing the reproduction, numbers, or distribution of any listed species (U.S. EPA 2004). After
the Agency s screening-level risk assessment is performed, if any of the Agency s Listed Species
LOG Criteria are exceeded for either direct or indirect effects, a determination is made to identify
if any listed or candidate species may co-occur in the area of the proposed pesticide use. If
determined that listed or candidate species may be present in the proposed use areas, further
biological assessment is undertaken. The extent to which listed species may be at risk then
determines the need for the development of a more comprehensive consultation package as
required by the Endangered Species Act.
For certain use categories, the Agency assumes there will be minimal environmental
exposure, and only a minimal toxicity data set is required (Overview of the Ecological Risk
Assessment Process in the Office of Pesticide Programs U.S. Environmental Protection Agency -
Endangered and Threatened Species Effects Determinations, 1/23/04, Appendix A, Section IIB,
pg.81). Chemicals in these categories therefore do not undergo a full screening-level risk
assessment, and are considered to fall under a no effect determination. The active ingredient
uses of l,2-benzisothiazolin-3-one fall into this category.
The inert uses of l,2-benzisothiazolin-3-one are also considered to fall under a "no effect"
determination, for the following reasons:
1. The allowable amount that can be applied is small (not more than 0.1%
formulation and 0.02 Ibs. per acre).
2. Data indicate that l,2-benzisothiazolin-3-one breaks down quickly in aerobic
soils (half-life < 24 hours in sandy loam soil).
3. l,2-Benzisothiazolin-3-one s ready biodegradation in soil and small
application result in minimal to no terrestrial or aquatic organism exposure.
b. General Risk Mitigation
BIT end-use products (EPs) may also contain other registered pesticides. Although the
Agency is not proposing any mitigation measures for products containing BIT specific to
federally listed species, the Agency needs to address potential risks from other end-use products.
Therefore, the Agency requires that users adopt all listed species risk mitigation measures for all
active ingredients in the product. If a product contains multiple active ingredients with
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conflicting listed species risk mitigation measures, the more stringent measure(s) should be
adopted.
V. What Registrants Need to Do
The Agency has determined that BIT is eligible for reregistration provided that: (i)
additional data that the Agency intends to require confirm this decision; and (ii) the risk
mitigation measures outlined in this document are adopted, and (iii) label amendments are made
to reflect these measures. The additional data requirements that the Agency intends to obtain
will include, among other things, submission of the following:
For BIT technical grade active ingredient products, the registrant needs to submit the
following items:
Within 90 days from receipt of the generic data call in (DCI):
1. completed response forms to the generic DCI (i.e., DCI response form and
requirements status and registrant's response form); and
2. submit any time extension and/or waiver requests with a full written justification.
Within the time limit specified in the generic DCI:
1. cite any existing generic data which address data requirements or submit new generic
data responding to the DCI.
Please contact Rebecca M. Miller at (703) 305-0012 with questions regarding generic
reregistration.
By US mail: By express or courier service:
Document Processing Desk (DCI/AD) Document Processing Desk (DCI/AD)
Rebecca M. Miller Rebecca M. Miller
US EPA (75 IOC) Office of Pesticide Programs (75 IOC)
1200 Pennsylvania Ave., NW Room 266A, Crystal Mall 2
Washington, DC 20460 1801 S. Bell Street
Arlington, VA 22202
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For end use products containing the active ingredient BIT, the registrant needs to submit the
following items for each product.
Within 90 days from the receipt of the product-specific data call-in (PDCI):
1. completed response forms to the PDCI (i.e., PDCI response form and requirements
status and registrant's response form); and
2. submit any time extension or waiver requests with a full written justification.
Within eight months from the receipt of the PDCI:
1. two copies of the confidential statement of formula (EPA Form 8570-4);
2. a completed original application for reregistration (EPA Form 8570-1). Indicate on
the form that it is an "application for reregistration";
3. five copies of the draft label incorporating all label amendments outlined in Table 23
of this document;
4. a completed form certifying compliance with data compensation requirements (EPA
Form 8570-34); and
5. if applicable, a completed form certifying compliance with cost share offer
requirements (EPA Form 8570-32); and
6. the product-specific data responding to the PDCI.
Please contact Marshall Swindell at (703) 308-8045 with questions regarding product
reregistration and/or the PDCI. All materials submitted in response to the PDCI should be
addressed as follows:
By US mail: By express or courier service:
Document Processing Desk (PDCI/PRB) Document Processing Desk (PDCI/PRB)
Marshall Swindell Marshall Swindell
US EPA (7508C) Office of Pesticide Programs (7508C)
1200 Pennsylvania Ave., NW Room 266A, Crystal Mall 2
Washington, DC 20460 1801 South Bell Street
Arlington, VA 22202
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A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic database supporting the reregistration of BIT has been reviewed and
determined to be substantially complete. However, the following additional data requirements
have been identified by the Agency as confirmatory data requirements. A generic data call-will
be issued at a later date.
An acute inhalation study is required for the technical grade active ingredient based on
new waiver criteria and advances in inhalation technology which nullified the previous waiver.
The chemical structure of BIT is not believed to be so closely related to CMIT/MIT that
an argument can be made to bridge carcinogenicity data for CMIT/MIT to BIT. Therefore, EPA
requires that the registrant submit carcinogenicity data for BIT to support the metal working fluid
use. Conversely, the registrant may claim that a carcinogenicity study would not be required for
the metalworking fluid use if the use is for "enclosed metalworking systems". Under this
scenario, it has been determined that certain toxicology data requirements including
carcinogenicity testing would be held in reserve pending review of worker exposure in such
enclosed systems.
The Agency has established an interim two-tiered system for toxicology testing
requirements. Tier I toxicology data requirements would apply to all indirect food additives that
result in residue concentrations ranging from 0-200ppb which applied to BIT. The requirements
would consist of an acute toxicity testing battery, subchronic toxicity study in the rodent, a
developmental toxicity study in the rat, and a mutagenicity testing battery. Each of these data
requirements has been fulfilled for BIT. The Agency also conducts a literature search and can
also conduct a Structural Activity Review (S AR) if appropriate. The Agency also will hold in
reserve a two-generation reproduction toxicity study in the rat and a subchronic toxicity studies
in a non-rodent which would become data requirements if the Agency's evaluation of the Tier 1
data warranted. A 2-generation reproduction study is being held in reserve for BIT. A
subchronic toxicity study in a non-rodent species is available for BIT.
Tier II studies would be triggered by the presence of significant (i.e. >200ppb) residues in
food or evidence of significant toxicity from the Tier I data set, which may include
developmental / reproductive, or other systemic toxicity such as presence of neoplastic growth or
significant target organ toxicity. In such cases, chronic toxicity and carcinogenicity testing would
be required.
The risk assessment noted deficiencies in the surrogate dermal and inhalation exposure
data available from the Chemical Manufacturers Association (CMA) data base. Therefore, the
Agency is requiring confirmatory data to support the uses assessed with the CMA exposure data
within this risk assessment. The risk assessment also noted that many of the use parameters
(e.g., amount handled and duration of use) were based on professional judgments. Therefore,
descriptions of human activities associated with the uses assessed are required as confirmatory.
To support the oil recovery uses of BIT, the following ecological effects data are needed:
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850.1075 (Old 72-1) Freshwater fish acute toxicity test with a warmwater species,
preferably Bluegill sunfish, using TGAI
850.1075 (old 72-3) Marine/estuarine fish acute toxicity test, preferably with Sheepshead
minnow, using TGAI
Table 21. Confirmatory Data Requirements for Reregistration
Guideline Study Name
Acute Inhalation Toxicity, using TGAI
Estuarine/Marine Fish Acute Toxicity, preferably
with Sheepshead minnow, using TGAI
Freshwater Fish Acute Toxicity with a
warmwater species, preferably Bluegill sunfish,
using TGAI
Indoor Inhalation Exposure and Applicator
Exposure Monitoring Data Reporting
Indoor Dermal Exposure and Applicator
Exposure Monitoring Data Reporting
Descriptions of Human Activity
Carcinogenicity
New OPPTS
Guideline No.
870.1300
850.1075
850.1075
875. 1400 and
875.1600
875. 1200 and
875.1600
875.2800
870.4200
Old Guideline No.
81-3
72-3
72-1
234 and 236
233 and 236
133-1
83-2
Studies Held in Reserve
2-Generation Reproduction
870.3800
83-4
2. Labeling for Technical and Manufacturing Use Products
To ensure compliance with FIFRA, technical and manufacturing use product (MP)
labeling should be revised to comply with all current EPA regulations, PR Notices and
applicable policies.
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific
data regarding the pesticide after a determination of eligibility has been made. The Registrant
must review previous data submissions to ensure that they meet current EPA acceptance criteria
and if not, commit to conduct new studies. If a registrant believes that previously submitted data
meet current testing standards, then the study MRID numbers should be cited according to the
instructions in the Requirement Status and Registrants Response Form provided for each
product.
A product-specific data call-in will be issued at a later date.
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2. Labeling for End-Use Products
No specific labeling changes are necessary to implement measures outlined in Section IV
above. However, to ensure compliance with FIFRA end use product (MP) labeling should be
revised to comply with all current EPA regulations, PR Notices and applicable policies.
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