Document ID: EPA-HQ-OPP-2007-0540-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-07-18T04:00Z

DRAFT

Bromonitrosytrene (BNS)

Occupational and Residential Exposure Assessment

Office of Pesticide Programs

Antimicrobials Division

U.S. Environmental Protection Agency

One Potomac Yard

2777 South Crystal Drive

Arlington, VA 22202-4501

Date: June 25, 2007

TABLE OF CONTENTS

  TOC \o "1-3" \h \z \u    HYPERLINK \l "_Toc125183615"  EXECUTIVE
SUMMARY	  PAGEREF _Toc125183615 \h  2  

  HYPERLINK \l "_Toc125183616"  1.0	 INTRODUCTION	  PAGEREF
_Toc125183616 \h  6  

  HYPERLINK \l "_Toc125183617"  1.1	Purpose	  PAGEREF _Toc125183617 \h 
6  

  HYPERLINK \l "_Toc125183618"  1.2	Criteria for Conducting Exposure
Assessments	  PAGEREF _Toc125183618 \h  6  

  HYPERLINK \l "_Toc125183619"  1.3	Chemical Identification	  PAGEREF
_Toc125183619 \h  8  

  HYPERLINK \l "_Toc125183620"  1.4	Physical/Chemical Properties	 
PAGEREF _Toc125183620 \h  8  

  HYPERLINK \l "_Toc125183621"  2.0	 USE INFORMATION	  PAGEREF
_Toc125183621 \h  9  

  HYPERLINK \l "_Toc125183622"  2.1	 Formulation Types and Percent
Active Ingredient	  PAGEREF _Toc125183622 \h  9  

  HYPERLINK \l "_Toc125183623"  2.2	 Summary of Use Pattern and
Formulations	  PAGEREF _Toc125183623 \h  9  

  HYPERLINK \l "_Toc125183624"  3.0	SUMMARY OF TOXICITY DATA	  PAGEREF
_Toc125183624 \h  10  

  HYPERLINK \l "_Toc125183625"  3.1	Acute Toxicity	  PAGEREF
_Toc125183625 \h  10  

  HYPERLINK \l "_Toc125183626"  3.2	Summary of Toxicity Endpoints	 
PAGEREF _Toc125183626 \h  11  

  HYPERLINK \l "_Toc125183627"  3.3	FQPA Considerations	  PAGEREF
_Toc125183627 \h  13  

  HYPERLINK \l "_Toc125183628"  4.0	RESIDENTIAL EXPOSURE ASSESSMENT	 
PAGEREF _Toc125183628 \h  13  

  HYPERLINK \l "_Toc125183629"  4.1	Summary of Registered Uses	  PAGEREF
_Toc125183629 \h  13  

  HYPERLINK \l "_Toc125183630"  4.2	Residential Exposure	  PAGEREF
_Toc125183630 \h  14  

  HYPERLINK \l "_Toc125183631"  4.2.1	Residential Handler Exposures	 
PAGEREF _Toc125183631 \h  14  

  HYPERLINK \l "_Toc125183632"  4.2.2	Residential Post-application
Exposures	  PAGEREF _Toc125183632 \h  16  

	4.2.2.1	Textiles
……..………………………………………………………
………….………………16

         4.2.3    	Data
Limitations/Uncertainties………………………………………
………………………..19

  HYPERLINK \l "_Toc125183633"  5.0	RESIDENTIAL AGGREGATE RISK
ASSESSMENT AND CHARACTERIZATION 	  PAGEREF _Toc125183633 \h  20  

  HYPERLINK \l "_Toc125183634"  6.0	OCCUPATIONAL EXPOSURE ASSESSMENT	 
PAGEREF _Toc125183634 \h  20  

  HYPERLINK \l "_Toc125183635"  6.1 	Occupational Handler Exposures	 
PAGEREF _Toc125183635 \h  22  

  HYPERLINK \l "_Toc125183636"  6.2  	Occupational Post-application
Exposures	  PAGEREF _Toc125183636 \h  25  

  HYPERLINK \l "_Toc125183642"  6.4	Data Limitations/Uncertainties	 
PAGEREF _Toc125183642 \h  27  

  HYPERLINK \l "_Toc125183643"  7.0	REFERENCES	  PAGEREF _Toc125183643
\h  29  

  HYPERLINK \l "_Toc125183645"  APPENDIX A: Summary of CMA and PHED Data
  PAGEREF _Toc125183645 \h  30  

 

EXECUTIVE SUMMARY 

	This document is the Occupational and Residential Exposure Chapter of
the Reregistration Eligibility Decision (RED) document for
bromonitrosytrene (BNS). It addresses the potential risks to humans that
result from its direct use in occupational settings and resulting
treated articles in residential settings.  

	BNS is used as a fungicide, slimicide, molluscide, mildewcide,
algaecide, and microbicide/microbiostat. The single product containing
BNS as the active ingredient (ai) is formulated as a soluble
concentrate. The concentration of BNS in this product is 25 percent. 
The product is used in the following use categories:  commercial/
institutional/industrial premises and equipment, material preservatives,
and industrial processes and water systems.  Examples of uses for BNS in
these settings include its use by commercial painters (in-can
preservative), as a material preservative incorporated into textiles,
metalworking fluids, oil recovery drilling muds and packer fluids, latex
paints, liquid detergents, , etc, and in industrial process water
systems such as pulp and paper mills, cooling tower water (once through
cooling towers), etc.  

	The durations and routes of exposure evaluated in this assessment
include short-term (ST), intermediate-term (IT), and/or long-term (LT)
durations for the inhalation, dermal, and oral routes of exposure.  The
inhalation endpoint (ST/IT/LT durations) is based on a 28-day oral
toxicity study in rats.  The NOAEL of 37 mg/kg/day is for all durations.
 The adverse effect for this endpoint is based on histopathology
findings in the fore stomach. For the incidental ingestion exposure
scenarios, the ST/IT oral endpoint (NOAEL of 37 mg/kg/day) is based on
the same study and same adverse effect.  The ST/IT/LT dermal endpoint
for systemic effects is based on a 21-day dermal toxicity study in
rabbits.  The effects observed in the dermal study were mortality in 2/5
females, reduced mean body weights in both sexes, and statistically
significant elevations in serum potassium levels in both males and
females.  The dermal NOAEL from this study is 50 mg/kg/day.  Because the
toxicological endpoints selected for inhalation, dermal, and oral routes
of exposure are not female-specific, a body weight of 70 kilograms is
used in the assessment.  EPA’s level of concern (LOC) for occupational
and residential BNS ST/IT/LT inhalation, ST/IT dermal, and ST oral
routes of exposures is 100 (i.e., a margin of exposure (MOE) less than
100 exceeds the level of concern). The level of concern is based on 10x
for interspecies extrapolation and 10x for intraspecies variation.  An
additional 3x data base uncertainty factor is applied to the IT
incidental oral and an additional 3x uncertainty factor is applied to
the LT dermal endpoint for use of a subchronic endpoint for the LT
endpoint.   

		This occupational and residential assessment was based on examination
of the single product label that describes the uses.  It has been
determined that there are no residential products that are applied
directly.  Only the use of BNS as an in-can preservative applies to
residential handlers.  Occupational handlers may be exposed in the
manufacturing of other products (e.g., textiles, paints, etc), during
treatment of water systems, commercial painters, and metalworking fluids
(MWF).  Post-application exposures are likely to occur in residential
settings by contacting treated articles such as clothing.  The
representative scenarios selected by EPA for assessment were evaluated
using maximum application rates as stated on the product label.  The
representative scenarios are believed to represent high-end uses
resulting in dermal, inhalation, and incidental oral exposures.

To assess the handler risks, EPA used surrogate unit exposure data from
the Chemical Manufacturers Association (CMA) antimicrobial exposure
study and the Pesticide Handlers Exposure Database (PHED).  Post
application/bystander exposures were assessed using EPA’s standard
assumptions (e.g., Health Effects Division’s (HED) Standard Operating
Procedures (SOPs) for Residential Exposure Assessment).  

Residential Handler Risk Summary

Dermal

	The residential handler dermal exposure scenarios are best represented
by the short-term duration (i.e., painting with a brush and airless
sprayer are considered to be intermittent in nature).  The short-term
dermal MOEs for the paint brush and airless sprayer are 1,500 and 590,
respectively.  The residential scenarios assume no PPE.

Inhalation

		For the residential painting inhalation assessment, the inhalation
MOEs were above the target MOE of 100 for all scenarios, and therefore,
are not of concern (and no need for a confirmatory inhalation toxicity
study).

Residential Post Application/Bystander Risk Summary

Dermal & Oral

	The residential post-application short- and intermediate-term dermal
and incidental oral risks were assessed for children and/or adults
coming in contact with or wearing treated textiles such as clothing. 
Dermal risks for toddlers and adults are not of concern even when 100%
residue transfer is assumed from treated clothing (i.e., toddler dermal
MOE = 170 and adult dermal MOE = 260).  In addition, the incidental oral
exposures from children mouthing treated fabric is not of concern (oral
MOE = 14,000).  Because a 100% transfer of residues is used in the
assessment, a confirmatory residue transfer study is not required.

Inhalation 

	Based on the application methods, inhalation exposure is expected to be
minimal. 

Occupational Handler Risk Summary

Dermal

For the occupational handler dermal exposure and risk assessment, the
MOEs were above the target MOE of 100 for all scenarios, and therefore,
are not of concern (Note:  Closed systems are required for the pulp &
paper, cooling water, and drilling muds for large applications).

Inhalation

	For the occupational handler inhalation exposure and risk assessment,
the MOEs were above the target MOE of 100 for all scenarios, and
therefore, are not of concern (Note:  Closed systems are required for
the pulp & paper, cooling water, and drilling muds for large
applications).   

  

Occupational Post Application/Bystander Risk Summary

	Based on the application methods, inhalation post-application exposures
are expected to be minimal.

Data Limitations and Uncertainties:

	There are a number of uncertainties associated with this assessment and
these have been reiterated from Sections 4.2.3 (residential) and 6.4
(occupational).  The data limitations and uncertainties associated with
the residential handler and post-application exposure assessments
include the following:

Surrogate dermal and inhalation unit exposure values were taken from the
proprietary Chemical Manufacturers Association (CMA) antimicrobial
exposure study (USEPA, 1999: DP Barcode D247642) or from the Pesticide
Handler Exposure Database (USEPA, 1998) (See Appendix B for summaries of
these data sources). Most of the CMA data are of poor quality therefore,
EPA requests that confirmatory monitoring data be generated to support
the values used in these assessments.  

The quantities handled/treated were estimated based on information from
various sources, including HED’s Standard Operating Procedures (SOPs)
for Residential Exposure Assessments (USEPA 2000, and 2001).  In certain
cases, no standard values were available for some scenarios. 
Assumptions for these scenarios were based on EPA estimates and could be
further refined from input from registrants. 

	The data limitations and uncertainties associated with the occupational
handler and post-application exposure assessments include:

Surrogate dermal and inhalation unit exposure values were taken from the
proprietary Chemical Manufacturers Association (CMA) antimicrobial
exposure study (USEPA, 1999: DP Barcode D247642) or from the Pesticide
Handler Exposure Database (USEPA, 1998) (See Appendix B for summaries of
these data sources).  Since the CMA data are of poor quality, the Agency
requests that confirmatory data be submitted to support the occupational
scenarios assessed in this document.

The quantities handled/treated were estimated based on information from
various sources, including HED’s Standard Operating Procedures (SOPs)
for Residential Exposure Assessments (USEPA 2000, and 2001) and personal
communication with experts.  The individuals contacted have experience
in these operations and their estimates are believed to be the best
available without undertaking a statistical survey of the uses.  In
certain cases, no standard values were available for some scenarios. 
Assumptions for these scenarios were based on EPA estimates and could be
further refined from input from registrants.  1.0	 INTRODUCTION tc \l1
"1.0	 INTRODUCTION 

		1.1	Purpose  tc \l2 "1.1	Purpose  

		In this document, EPA’s Antimicrobials Division (AD) presents the
results of its review of the potential human health effects of
occupational and residential exposure to bromonitrosytrene (BNS)
(beta-Bromo-beta-nitrostyrene), case number 2065. The information
presented in this Occupational and Residential Exposure chapter is for
use in EPA's development of the BNS Reregistration Eligibility Decision
(RED) document. 

		1.2	Criteria for Conducting Exposure Assessments tc \l2 "1.2	Criteria
for Conducting Exposure Assessments 

		An occupational and/or residential exposure assessment is required for
an active ingredient if (1) certain toxicological criteria are triggered
and (2) there is potential exposure to handlers (mixers, loaders,
applicators, etc.) during use or to persons entering treated sites after
application is complete.  For BNS, both criteria are met. Toxicological
endpoints were selected for short- and intermediate-term dermal,
inhalation, and incidental oral exposures to BNS.  There is the
potential for exposure in a variety of occupational and residential
settings.  Therefore, risk assessments are required for occupational and
residential handlers as well as for occupational and residential post
application exposures that can occur as a result of BNS use.

In this document, handler scenarios were assessed by using unit exposure
data to estimate occupational and residential handlers’ exposures.
Unit exposures are estimates of the amount of exposure to an active
ingredient a handler receives while performing various handler tasks and
are expressed in terms of micrograms or milligrams (1 mg = 1,000 µg) of
active ingredient per pounds of active ingredient handled.  A series of
unit exposures have been developed that are unique for each scenario
typically considered in assessments (i.e., there are different unit
exposures for different types of application equipment, job functions,
and levels of protection).  The unit exposure concept has been
established in the scientific literature and also through various
exposure monitoring guidelines published by the USEPA and international
organizations such as Health Canada and OECD (Organization for Economic
Cooperation and Development).  

Using surrogate unit exposure data, maximum application rates from
labels, and EPA estimates of daily amount handled, exposures and risks
to handlers were assessed.  The exposure/risks were calculated using the
following equations:

Daily Exposure: Daily inhalation and dermal handler exposures are
estimated for each applicable handler task with the application rate,
quantity treated/handled in a day, and the applicable inhalation unit
exposure using the following formula:

Daily Exposure:	E = UE x AR x AT					(Eq. 1)

Where:  

E	=	Amount (mg ai/day) inhaled or contacted dermally that is available
for absorption;

UE	=	Unit exposure value (mg ai/lb ai) derived from August 1998 PHED
data or from 1992 CMA data;

AR	=	Maximum application rate based on a logical unit treatment, such as
square feet (sq. ft.), gallons (gal), or cubic feet (cu. ft). Maximum
values are generally used (lb ai/sq ft, lb ai/gal, lb ai/cu ft); and

AT 	=	Normalized application area based on a logical unit treatment such
as  square feet  (sq ft/day), gallons (gal/day), or cubic feet (cu
ft/day).

Daily Dose: The inhalation and dermal doses are calculated by
normalizing the daily exposure by body weight and adjusting, if
necessary, with an appropriate absorption factor.  An absorption factor
of 100% was used for inhalation exposures.  An absorption factor was not
necessary for dermal exposures because a route-specific dermal endpoint
is available.  Daily dose was calculated using the following formula:

Daily Dose:	ADD = E x ABS							(Eq. 2)

			   BW						

Where:

ADD 		= 	Average daily dose or the absorbed dose received from exposure
to a chemical in a given scenario (mg active ingredient/kg body
weight/day);

E 		=	Amount (mg ai/day) inhaled or contacted dermally that is available
for absorption;

ABS 		= 	A measure of the amount of chemical that crosses a biological
boundary such as lungs (% of the total available absorbed); and

BW		= 	Body weight determined to represent the population of interest in
a risk assessment (kg).

Margins of Exposure:  Non-cancer inhalation and dermal risks for each
applicable handler scenario are calculated using a Margin of Exposure
(MOE).  This is the ratio of the daily inhalation or dermal dose to the
toxicological endpoint of concern.  

Margins of Exposure:			MOE = NOAEL or LOAEL			(Eq. 3)

							ADD

Where:

MOE 			= 	Margin of exposure, value used to represent risk or how close
a chemical exposure is to being a concern (unitless);

NOAEL or LOAEL	= 	Systemic toxicity level where no observed adverse
effects (NOAEL) or where the lowest observed adverse effects (LOAEL)
occurred in the study (mg ai/kg body weight/day); and

ADD 			= 	Average daily dose in a given scenario (mg ai/kg body
weight/day).

	In addition to the target MOEs presented in Table 3.2 that were used
for the analysis, a series of assumptions and exposure factors served as
the basis for completing the handler risk assessment. Each general
assumption and factor for both residential and occupational assessments
is detailed below.  Assumptions specific to the use site category are
listed in each separate section of this document.  The general
assumptions and factors include:

The BNS product has a large number of use patterns that are difficult to
completely capture in this document.  As such, EPA has patterned this
risk assessment on a series of likely representative scenarios for each
use site that are believed by EPA to represent the vast majority of BNS
uses.

Based on the adverse effects for the endpoints, the body weight of 70 kg
is used for the inhalation and dermal and oral routes of exposure.  

Exposure factors used to calculate daily exposures to handlers were
based on applicable data, if available.  When appropriate data were
lacking, values from a scenario deemed similar were used. 

The maximum application rates allowed by labels were assumed. 	

Chemical Identification

		

		BNS (beta-Bromo-beta-nitrostyrene) was first registered with the EPA
in 1972.  Its CAS number is 7166-19-0.  Figure 1 illustrates the
molecular structure of BNS.

 

					Figure 1.  Molecular Structure of Bromonitrostyrene

		1.4	Physical/Chemical Properties tc \l2 "1.4	Physical/Chemical
Properties 

		Table 1.2 shows physical/chemical characteristics that have been
reported for BNS.

Table 1.2.  Physical/Chemical Properties of BNS

Parameter	

BNS

Molecular Weight	228

Density	2.2753 g/ml @ 20˚C (8.2 lbs/gal @ 25% ai)

Boiling Point	Solid

Water Solubility	0.001 g/100 ml (10 ppm)

Vapor Pressure	 4.14E-4 mm Hg at 25˚C 

2.0	 USE INFORMATION tc \l1 "2.0	 USE INFORMATION 

		2.1	 Formulation Types and Percent Active Ingredient tc \l2 "2.1	
Formulation Types and Percent Active Ingredient 

		BNS is used as a fungicide, slimicide, molluscide, mildewcide,
algaecide, and microbicide/microbiostat. The single product containing
BNS as the active ingredient (ai) is formulated as a soluble concentrate
(EPA Reg. No. 464-686). The concentration of BNS in this product is 25
percent.  

 

		2.2	 Summary of Use Pattern and Formulations

	The Agency determines potential exposures to handlers of pesticide
products by identifying exposure scenarios from the various application
methods that are plausible, given the labeled uses.  The following Use
Site Categories (USC) were identified based on a review of the BNS
product label: 

(III)   SEQ CHAPTER \h \r 1 Commercial, institutional and industrial
premises and equipment, 

(VII)   SEQ CHAPTER \h \r 1 Material preservatives, and 

(VIII) Industrial processes and water systems. 

	Specific uses within these use categories are identified in Table 2.1. 
From Table 2.1, EPA has selected representative exposure scenarios to
assess BNS in this document.  These scenarios were selected to be
representative of the vast majority of uses and are believed to provide
high-end degrees of dermal, inhalation, or incidental ingestion
exposure.  The representative scenarios assessed in this document are
shown in Table 4.1 (residential) and Table 6.1 (occupational).

Table 2.1. Potential Use Scenarios Based on Product Labels for BNS.

Use Site Category	

Example Use Sites	

Scenarios

Use Site Category 

III	

Commercial/ Institutional/Industrial	

Commercial laundry	

Liquid pour

Use Site Category VII

Material Preservatives	

Used in the preservation of various products such as paints, leather,
textiles, MWF, etc	Liquid pour

Liquid pump

Painting

MWF machinists 

textiles

Use Site Category VIII

Industrial Processes and water systems	

Used in water systems such as pulp & paper mills, cooling tower water,
oil recovery injection water, etc.	

Liquid pour

Liquid pump

3.0	SUMMARY OF TOXICITY DATA tc \l1 "3.0	SUMMARY OF TOXICITY CONCERNS
RELATING TO EXPOSURE 

	3.1	Acute Toxicity

 tc \l2 "3.1	Acute Toxicity 

	The acute toxicity data for BNS are summarized below in Table 3.1.

Table 3.1.  Acute Toxicity Profile for Bromonitrostyrene

Guideline Number	Study Type/

Test substance (% a.i.)	MRID Number/

Citation	Results	Toxicity Category

870.1100

	Acute Oral- Rat

Giv 2-0820 (99.1% a.i.) 	41603501	LD50(M): 446 mg/kg LD50(F): 466 mg/kg
LD50(M/F): 457 mg/kg	II

870.1100 	Acute Oral- Rat

ß-bromo-ß-nitrostyrene 

(25.1% a.i.)	41603506	LD50(M): 1837 mg/kg LD50(F): 1464 mg/kg LD50(M/F):
1678 mg/kg	III

870.1200

	Acute Dermal- Rabbit

Giv-Gard BNS (25% a.i.) 	44524506	LD50: > 2000 mg/kg bw	III

870.1300

	Acute Inhalation- Rat

Bromonitrostyrene 

(98.2% a.i.)	43452701	LC50(M): 0.14 mg/L

LC50 (F): 0.30 mg/L

LC50 (M/F): 0.20 mg/L	II

870.2400

	Primary Eye Irritation- Rabbit

Giv-Gard BNS (25% a.i.)	44524509	Moderate to Severe Irritant	II

870.2500

	Primary Dermal Irritation- Rabbit           

ß-bromo-ß-nitrostyrene (25.1% a.i.)	41744601	Corrosive	I

870.2500

	Primary Dermal Irritation- Rabbit           Bromonitrostyrene (25%
a.i.)	44178401	Corrosive	I

870.2500

	Primary Dermal Irritation- Rabbit           Giv-Gard BNS (25% a.i.)
44524508	Severe, Reversible Dermal Irritation	II

870.2600	Dermal Sensitization – Guinea Pig 

Giv-Gard BNS (25% a.i.)	44524510	Moderate Sensitization	N/A

870.2600	Dermal Sensitization – Guinea Pig 

Spectrum RX4101 (9.2% a.i.)	45094806	Moderate Sensitization	N/A

	3.2	Summary of Toxicity Endpoints tc \l2 "3.2	Summary of Toxicity
Concerns Relating to Exposures 

	Table 3.2 summarizes the toxicological endpoints for BNS.  

	

Table 3.2.  Summary of Toxicological Doses and Endpoints for
Bromonitrostyrene

Exposure

Scenario	

Dose Used in 

Risk Assessment

(mg/kg/day) 	

Target MOE, UF, Special FQPA SF, for Risk Assessment	

Study and 

Toxicological Effects

Dietary Risk Assessments

Acute Dietary

(all populations)

	

NOAEL = 37 

	

UF = 100 (10x inter-species extrapolation, 10x intra-species variation)

	

28-day (Oral) Toxicity Study in Rats (NTP study) 

LOAEL = 75 mg/kg/day based on histopathology findings in the forestomach

	

aRfD = 0.37 mg/kg/day

Chronic Dietary

(all populations)	

NOAEL = 37	

UF = 100 (10x inter-species extrapolation, 10x intra-species variation,
10x database uncertainty)	

28-day (Oral) Toxicity Study in Rats (NTP study) 

LOAEL = 75 mg/kg/day based on histopathology findings in the forestomach

	

cRfD = 0.037 mg/kg/day

Non Dietary Risk Assessments

Incidental Oral

Short-Term

 (1-30days 	NOAEL=37 

	Residential = 100 (10x inter-species extrapolation, 10x intra-species
variation)

Occupational = NA	28-day (Oral) Toxicity Study in Rats (NTP study) 

LOAEL = 75 mg/kg/day based on histopathology findings in the forestomach

Incidental Oral

Intermediate-Term

(1-6 months)  	NOAEL=37 

	Residential = 300 (10x inter-species extrapolation, 10x intra-species
variation and 3x database uncertainty)

Occupational = NA	28-day (Oral) Toxicity Study in Rats (NTP study) 

LOAEL = 75 mg/kg/day based on histopathology findings in the forestomach

Dermal

Short-Term (1-30 days) and Intermediate-Term

(1-6 months)

	NOAEL (systemic) = 50 	MOE = 100 (10x inter-species extrapolation, 10x
intra-species variation)	21-Day (Dermal) Subchronic Toxicity Study in
Rabbits (MRID 40830101)

LOAEL = 100 mg/kg/day based on mortality in 2/5 females, reduced mean
body weights in both sexes, and statistically significant elevations in
serum potassium levels in both males and females.

Dermal

Long-Term

(> 6 months)	NOAEL (systemic) = 50 	MOE = 300 (10x inter-species
extrapolation, 10x intra-species variation, 3x for use of a subchronic
endpoint for the long-term endpoint) 	21-Day (Dermal) Subchronic
Toxicity Study in Rabbits (MRID 40830101)

LOAEL = 100 mg/kg/day based on mortality in 2/5 females, reduced mean
body weights in both sexes, and statistically significant elevations in
serum potassium levels in both males and females.

Inhalation

(All Durations)	NOAEL = 37	MOE = 100a 

(10x inter-species extrapolation, 10x intra-species variation)   

	28-day (Oral) Toxicity Study in Rats (NTP study) 

LOAEL = 75 mg/kg/day based on histopathology findings in the forestomach

Cancer

(oral, dermal, inhalation)	No carcinogenicity data available for
bromonitrostyrene.

UF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL
= lowest observed adverse effect level, RfD = reference dose (a = acute
and c = chronic), MOE = margin of exposure

a  An extra 10x is used because the current inhalation endpoint is based
on an oral NOAEL, and although the target inhalation MOE is 100, if the
MOE is below 1,000, the Agency may request a confirmatory inhalation
toxicity study.

	3.3	FQPA Considerations 

	The hazard-based FQPA factor should be removed because the toxicology
data provided no indication of increased susceptibility of rats or
rabbits to in utero and/or postnatal exposure to BNS and there is no
evidence of developmental anomalies, including abnormalities in the
development of the fetal nervous system, in the pre- and/or post-natal
studies.  Additionally, there are no data gaps for evaluation of
increased susceptibility to infants and children.  

4.0	RESIDENTIAL EXPOSURE ASSESSMENT  tc \l1 "4.0	RESIDENTIAL EXPOSURE
ASSESSMENT 

	4.1	Summary of Registered Uses tc \l2 "4.1	Summary of Registered Uses 

	Although there are no registered products containing BNS that can be
applied directly by the homeowner, there is a homeowner application of
BNS when it is used as an in-can preservative for latex paint.  The
consumer and household product uses listed in EPA Reg. No. 464-686 for
dishwashing liquids, surface cleaners, laundry cleaners, and polishes
are no longer supported by the registrant.  Articles treated with BNS in
occupational settings may also have the potential for post-application
residential exposure.  BNS-treated articles that may routinely be used
in the residential market include, but are not limited to, material
preservative uses in clothing, leather, inks, and paper.  

	4.2	Residential Exposure tc \l2 "4.4	Residential Exposure/Risk Pathway 

	The exposure scenarios assessed in this document for the representative
uses of BNS selected by EPA are listed in Table 4.1. The table also
shows the maximum application rate associated with the representative
use and the EPA label registration number.  Handler dermal and
inhalation exposures are assessed for the in-can preservative use in
paint.  Post-application dermal, inhalation, and/or incidental ingestion
exposures are assessed for treated articles including clothing. 
Post-application/bystander inhalation exposures are expected to be
minimal for most uses, except for the airless spray painting.  The
inhalation bystander exposure to aerosols generated during painting are
assumed to be less then that of the applicator and are therefore not
assessed separately.  

Table 4.1. Representative Uses Associated with Residential Exposure to
BNS.

Representative Use	Application Method	Exposure Scenario	Example
Registration Number	Application Rate

Paint	Brush and airless sprayer	ST Handler:  adult dermal and
inhalation.	464-686	0.0005 lb ai/gallon

[2 lbs product x 25% ai / 1000 lb paint  = 0.0005 lb ai/gallon of paint;
or 2000 ppm product x 25% ai = 500 ppm BNS; or 0.05% BNS]

Textiles 

(exposures to treated  articles are represented by exposure to clothing)
NAa	ST Post-app: wearing treated clothing, adult dermal; child
incidental ingestion and dermal 	464-686	8.1E-5 lb ai/lb fabric or 80
ppm BNS

(1 oz product x 25% ai per 200 lbs fabric in final rinse; or 320 ppm
product x 25% ai = 80 ppm BNS )

a    The handlers scenarios were not assessed for residents because the
products can only be applied occupationally

		4.2.1	Residential Handler Exposures

	The residential handler scenarios described in Table 4.1 were assessed
to determine dermal and inhalation exposures.  The scenarios were
assessed using PHED and CMA data and the equations in Section 1.2,
“Criteria for Conducting Risk Assessment.”  A summary of the PHED
and CMA data sets are presented in Appendix A.

Unit Exposure Values: Unit exposure values were taken from the PHED data
presented in HED’s Residential SOPs (USEPA, 1997) and from the CMA
data from the EPA memorandum Evaluation of Chemical Manufacturers
Association Antimicrobial Exposure Assessment Study (USEPA, 1999).

    

For the airless sprayer scenario, PHED dermal and inhalation unit
exposure values for a residential handler applying a pesticide using an
airless sprayer were used.  These unit ungloved exposure values (79
mg/lb a.i. for dermal and 0.83 mg/lb a.i. for inhalation) represent a
handler painting a residential bathroom wearing short pants and a short
sleeve shirt, with no gloves. 

For the brush/roller scenario, PHED dermal and inhalation unit exposure
values for a residential handler applying a pesticide using a paint
brush were used.  These unit exposure values (230 mg/lb a.i. for dermal
and 0.28 mg/lb a.i. for inhalation) represent a handler wearing short
pants and a short sleeve shirt, with no gloves.

Quantity handled/treated: The quantities handled/treated were estimated
based on information from various sources, including EPA estimates. 

For the brush/roller in paint applications, it is assumed that 20 lbs
(approximately 2 gallons) of treated paint will be used.  This is based
on the 90th percentile value of 8 gallons of latex paint used per year
divided by the mean frequency of 4 painting events/year.  

For the airless sprayer in paint applications, it is assumed that 150
lbs           (approximately 15 gallons) of treated paint will be used. 
This is based on the coverage of 200 ft2/gallon and a house size of 40 x
30 x 20 ft (surface area of 2,800 ft2).

Duration of Exposure: The duration of exposure for most handler
homeowner uses is believed to be best represented by the short-term
duration (1 to 30 days).  The reason that short term duration was chosen
to be assessed is because painting is episodic in nature, not daily.  In
addition, homeowners are assumed to use different products with varying
activities, not exclusively BNS treated products (e.g., in-can paint
preservative).

Results

	The resulting short-term inhalation and dermal exposures and MOEs for
the representative residential handler scenarios are presented in Tables
4.2.    The calculated inhalation MOEs are above the target MOE of 100
for all scenarios.  Therefore, the risks do not exceed EPA’s level of
concern.  In addition, the inhalation MOEs are greater then 1,000 using
the route-to-route extrapolation, and therefore, a confirmatory
inhalation study is not warranted for the residential paint application.

Table 4.2 BNS Short-Term Residential Handler Inhalation  and Dermal
MOEs.

Exposure Scenario

Application Method	Application Method	Application Ratea	Quantity
Handled/ Treated per dayb	

Unit Exposure

(mg/lb a.i.)	Daily Dose (mg/kg/day) c	MOE d 

(Target MOE = 100)

Inhalation	Dermal	Inhalation	Dermal	Inhalation	Dermal

Painting	Paint brush	0.0005 lb ai/gal

(0.05% ai)	2 gallons	0.28	230	4.1E-5	0.033	900,000	1,500

	Airless sprayer

15 gallons	0.83	79	0.00089	0.085	42,000	590

a	Application rates are the maximum application rates determined from
EPA registered label for BNS.

b	Amount handled per day values are estimated.	

c	Daily dose (mg/kg/day) = [unit exposure (mg/lb a.i.) x application
rate (% a.i. weight or lb ai/gal) x quantity treated (lb/day or gal/day)
x absorption factor (1.0 for inhalation and dermal)]/ Body weight (70
kg).

d	MOE = NOAEL / Daily Dose.  [Where short-term inhalation NOAEL = 37
mg/kg/day and the short-term dermal NOAEL = 50 mg/kg/day]. Target MOEs =
100.

	

 		4.2.2	Residential Post-application Exposures tc \l3 "4.4.2
Postapplication Exposure 

 	For the purposes of this screening level assessment, post-application
scenarios represent a high end exposure scenario for all products
represented. As shown in Table 4.1, representative post-application
scenarios assessed include wearing treated clothing (dermal exposure to
adults and children and incidental oral exposure to children). 

	4.2.2.1		Textiles

Dermal Exposure to Adults and Toddlers from Contacting Treated Clothing

	There is the potential for dermal exposure to adults and children from
wearing clothing treated via the final rinse during manufacturing as a
preservative (i.e., to prevent mildew in laundry or treated fabric).  A
post-application assessment assuming no laundering by the homeowner was
conducted as a conservative measure (i.e., the effect on dislodgeable
residues over time during washing is not quantifiable at this time).  It
should be noted that not all articles of clothing are treated with BNS
products or worn on a continuous basis.  In general, it is believed that
most treated textiles used in a residential setting will result in
exposures occurring over a short-term time duration (1 to 30 days)
because residents are assumed to be exposed to treated textiles with
varying active ingredients, not exclusively BNS treated textiles. 
Nonetheless, the short-term dermal toxicological endpoint is protective
of the intermediate-term duration because the same endpoint value is
used to assess both durations.

Exposure Calculations

Potential doses are calculated as follows:

PDD = W x % applied x % a.i. x % transfer

		           BW						

where: 

PDD		= 	potential daily dose (mg/kg/day);

W 		= 	weight of clothing worn (g/day);

% applied	= 	percent of product applied (%);

% a.i.		= 	percent active ingredient in product (%); 

% transfer	= 	percent transferred (%); and 

BW		=	body weight (kg).

And

W = (SW/SSA) * BSA										

where:

W	=	weight of clothing worn (g/day);

SW 	=	weight of medium shirt (g);

SSA 	= 	surface area of medium shirt (cm2); and

BSA	=	surface area of body covered (cm2).

Assumptions

The formulated product is applied at rates as high 320 ppm of product
which is 25% ai (0.032% product by weight) or 80 ppm BNS (i.e., 0.008%
ai by weight).

The median surface area of clothing contacting skin for a 3-year-old
toddler is 5,670 cm2 (total body surface area minus the head) (USEPA,
1997).  For adults, the median surface area is 16,900 cm2 (total body
surface area minus the head) (USEPA, 1997).  

The textile density is 10 mg/cm2 based on the density of mixed cotton
and synthetics (HERA 2003).  It is assumed that the mixed
cotton/synthetic is used to cover the body for both adults and toddlers,
minus the head surface area.  Therefore, the total amount of fabric worn
per day is equal to the density of the fabric (10 mg or 0.01 grams per
cm2) times the surface area covered (5,670 cm2 for toddlers, 16,900 cm2
for adults), or 56.7 g/day for toddlers, and 169 g/day for adults.

Potential doses were calculated using a conservative residue transfer
factor of 100%, which assumes that all residues are transferable from
clothing surfaces to the skin.  In cases where the MOEs did not meet the
Agency’s target MOE, potential doses were also calculated using a less
conservative residue transfer factor of 5%, which is based on the amount
of residue assumed to be transferable from carpeted surfaces (USEPA,
2000 and 2001).  In these cases, confirmatory data are needed to support
the use of the lower transfer factor.

Toddlers (3 years old) are assumed to weigh 15 kg. This is the mean of
the median values for male and female toddlers (USEPA, 1997).  For
adults, a body weight of 70 kg has been assumed. (USEPA, 1997).  

Results

	The calculations of the intermediate-term dermal doses and MOEs for
adults and toddlers wearing treated clothing are shown in Table 4.5. 
The dermal MOEs for adults and toddlers are greater than 100 assuming a
100% residue transfer factor.  Therefore, the risks are not of concern
and a confirmatory residue transfer factor/study is not warranted at
this time.

Table 4.5:  Dermal Post-application Exposures and MOEs for Toddlers and
Adults Contacting Treated Clothing

Exposure Scenario	Weight of clothing worn (g/day)a	Percent BNS in
product (%)	Percent of product applied (%)	Percent residue transferred
from clothing to skin (%)	Daily doseb  

(mg a.i./ kg/day)	Dermal MOEc (Target MOE=100)

Toddler	56.7	25%	0.032%	100	0.302	170

Adult	169	25%	0.032%	100	0.193	260

a.	Weight of clothing worn (g/day) = (Density of fabric 0.01 g/cm2) *
(surface area of body covered, cm2) * 1 outfit/day

b.	Absorbed Daily Dose (mg/kg/day) = [(weight of clothing worn, g/day) *
(percent a.i. in product, %) / 100 * (percent of product applied, %) /
100 * (percent residue transferred from clothing to skin, %) * (dermal
absorption factor, 1) * (conversion factor, 1000 mg/g)] / (body weight,
70 kg).

c. 	Dermal MOE = NOAEL (mg/kg/day) / Daily Dose [Where dermal NOAEL = 50
mg/kg/day].  Target MOE = 100.

Incidental Oral Exposure to Toddlers Mouthing Treated Textiles
(Clothing/Blankets)

Exposure Calculations 

	There is the potential for incidental oral exposure to toddlers from
mouthing textiles treated with BNS.

Potential doses are calculated as follows:

PDD = C x SE x SA 

	    BW							

where: 

PDD	= 	potential daily dose (mg/kg/day);

C 	= 	concentration on clothing (mg/cm2);

SE	=	saliva extraction efficiency (%);

SA 	= 	surface area mouthed (cm2/day); and

BW 	= 	body weight (kg).

And

C = % a.i. x % applied x W x CF1 x CF2									

where:

C		=	concentration on clothing (mg/cm2);

% applied	= 	percent of product applied (%);

% a.i.		= 	percent active ingredient in product (%); 

W 		= 	weight of clothing (g/m2);

CF1		=	unit conversion factor (1,000 mg/g); and

CF2		=	unit conversion factor (0.0001 m2/cm2).

Assumptions

The formulated product is applied at rates as high 320 ppm of product
which is 25% ai (0.032% product by weight) or 80 ppm BNS (i.e., 0.008%
ai by weight).

The textile density is 10 mg/cm2 based on the density of mixed cotton
and synthetics (HERA 2003).  

The saliva extraction efficiency was 50% (USEPA, 2000 and 2001).

The surface area of textiles mouthed by toddlers is 100 cm2
(professional judgment).

Toddlers (3 years old) are used to represent the 1 to 6 year old age
group.  For three-year olds, the median body weight is 15 kg (USEPA,
1997).

Results

    Table 4.6 shows the calculation of the short- and intermediate-term
oral dose and oral MOE for toddlers mouthing treated textiles. The MOE
value is greater than target MOE of 100 for the maximum concentration
allowed on the label (MOE = 14,000).  

Table 4.6:  Incidental Oral Exposures and MOEs for Toddlers Wearing
Treated Textiles (Clothing/Blankets)

Weight of clothing (g/cm2)	% Product Applied	Concentration on clothinga
(mg/cm2)	Surface area mouthed (cm2/day)	

Saliva extraction efficiency 

(%)	Potential daily dose 

(mg a.i./kg/day)	Incidental Oral MOEc (Target MOE =300)

0.01	0.032%	0.0008	100	50	0.0027	14,000

a.	Concentration on clothing (mg/cm2) = (25 percent a.i. in product, %)
/ 100 * (percent product applied, %) / 100 * (weight of clothing, g/cm2)
* 1,000 mg/g 

b.	Potential Daily Dose (mg/kg/day) = (concentration on clothing,
mg/cm2) * (surface area mouthed, cm2/day) * (saliva extraction
efficiency, %)/100 / (body weight, 15 kg).

c 	Oral MOE = NOAEL (mg/kg/day) / Potential Daily Dose [Where short- and
intermediate-term incidental oral NOAEL = 37 mg/kg/day].  Target MOE =
100.	

	4.2.3	Data Limitations/Uncertainties tc \l3 "4.4.3	Data
Limitations/Uncertainties 

	There are several data limitations and uncertainties associated with
the residential handler and post-application exposure assessments. 
These include the following:

Surrogate dermal and inhalation unit exposure values were taken from the
proprietary Chemical Manufacturers Association (CMA) antimicrobial
exposure study (USEPA, 1999: DP Barcode D247642) or from the Pesticide
Handler Exposure Database (USEPA, 1998) (See Appendix B for summaries of
these data sources). Most of the CMA data are of poor quality,
therefore, EPA requires that confirmatory monitoring data be generated
to support the values used in these assessments.  

The quantities handled/treated were estimated based on information from
various sources, including HED’s Standard Operating Procedures (SOPs)
for Residential Exposure Assessments (USEPA, 2000 and 2001).  In certain
cases, no standard values were available for some scenarios. 
Assumptions for these scenarios were based on EPA estimates and could be
further refined from input from registrants. 

RESIDENTIAL AGGREGATE RISK ASSESSMENT AND CHARACTERIZATION – 

	The residential uses that could potentially be aggregated are the paint
applications and the textiles.  The likelihood of co-occurrence is
minimal because of the limited frequency a resident paints coupled with
not all paints and/or textiles are treated with BNS.  Therefore,
residential uses are not recommended to be aggregated.  In addition, the
inhalation and dermal endpoints are based on different toxicological
effects, and therefore, it is not appropriate to estimate total MOEs
(same situation for the dermal and oral routes for postapplication).  
tc \l1 "5.0	RESIDENTIAL AGGREGATE RISK ASSESSMENTS AND RISK
CHARACTERIZATION 

	

6.0	OCCUPATIONAL EXPOSURE ASSESSMENT tc \l1 "6.0	OCCUPATIONAL EXPOSURE
AND RISK 

	The exposure scenarios assessed in this document for the representative
uses selected by EPA are shown in Table 6.1. The table also shows the
maximum application rate associated with the representative use and the
appropriate EPA Registration number for the product label.  It should be
noted that for the calculation of application rates in which 8.34 lb/gal
is noted, the product is assumed to have the density of water because no
product-specific density is available.   

	Potential occupational handler exposure for BNS can occur in three Use
Categories:   commercial/institutional/industrial premises and
equipment, material preservatives, and industrial processes and water
systems.

Table 6.1.  Representative Exposure Scenarios Associated with
Occupational Exposures to BNS

Representative Use	Method of Application	Exposure Scenario	Example
Registration #	Application Rate

Commercial/Industrial/Institutional Premises (Use Category III)

MWF Machinist	Liquid pour

Machinist	ST/IT/LT handler/machinist:

Dermal

Inhalation	464-686	500 ppm ai or 0.05% ai

[up to 2000 ppm product x 25% ai = 500 ppm BNS]

Painting 

(commercial painters)	Paint brush,

Airless sprayer	ST/IT Handler:

Inhalation

Dermal	464-686	0.0005 lb ai/gallon

[2 lbs product x 25% ai / 1000 lb paint  = 0.0005 lb ai/gallon of paint;
or 2000 ppm product x 25% ai = 500 ppm BNS; or 0.05% BNS]

Material Preservatives (Use Category VII)

Paint

	Liquid pour	ST/IT Handler: inhalation

dermal	464-686	0.0005 lb ai/gallon or 0.05% ai

[2 lbs product x 25% ai / 1000 lb paint  = 0.0005 lb ai/gallon of paint;
or 2000 ppm product x 25% ai = 500 ppm BNS; or 0.05% BNS]

  SEQ CHAPTER \h \r 1 Industrial processes and water systems (Use
Category VIII)

Pulp and Paper 

(mill process water) 	Metered pump

	ST/IT Handler: Inhalation

dermal

	464-686

	Initial:  0.075 lb ai/ton

Continuous:  0.05 lb ai/ton

[Initial:  0.3 lbs product/1 ton pulp/paper; 

Continuous feed: 0.2 lbs product/ 1 ton pulp.  

Where product is 25% ai x lb product/ton.]

Recirculating Cooling Water	Metered pump	ST/IT Handler: Inhalation

dermal	464-686	Initial:  18 ppm ai

Continuous:  5 ppm ai

[Initial:  0.6 lb product/1000 gal or 72 ppm product.

Continuous feed:  0.16 lb product/1000 gal or 20 ppm product.  

Where product is 25% ai x rate]

Once Through Cooling Water	Metered pump	ST/IT Handler: Inhalation

dermal	464-686	Maintenance:  9 ppm ai

Mollusca:   21 ppm ai

[Maintenance:  0.3 lb product/1000 gal or 36 ppm product.

Mollusca:  0.7 lb product/1000 gal or 84 ppm product.  

Where product is 25% ai x rate]

Packer Fluids and Drilling Muds	Liquid pour

Metered pump	ST/IT Handler: Inhalation

dermal	464-686	125 lb ai/ 1000 barrels or 200 ppm ai.

[500 lbs product x 25% ai / 1000 barrels = 125 lb ai/1000 barrels; or
800 ppm product x 25% ai = 200 ppm ai]

 

	6.1 	Occupational Handler Exposures

	The occupational handler scenarios included in Table 6.1 were assessed
to determine inhalation and dermal exposures.  The general assumptions
and equations that were used to calculate occupational handler
inhalation and dermal risks are provided in Section 1.2, Criteria for
Conducting the Risk Assessment. The majority of the scenarios were
assessed using CMA data and Equations 1-3.  However, for the
occupational scenarios in which CMA data were insufficient, other data
and methods were applied. 

	

Unit Exposure Values (UE):  Inhalation and dermal unit exposure values
were taken from the proprietary Chemical Manufacturers Association (CMA)
antimicrobial exposure study (USEPA, 1999b: DP Barcode D247642) or from
the Pesticide Handler Exposure Database (USEPA, 1998).

For the liquid pour scenarios for materials preservatives, the unit
exposure depends on the material being treated.  The following CMA unit
exposures were available and used for the assessment of the risk
associated with the treatment of the specified materials.

Metalworking fluid: CMA metal fluid gloved data.  The dermal UE is 0.184
mg/lb a.i. and the inhalation UE is 0.00854 mg/lb a.i.. The values are
based on 8 replicates where the test subjects were wearing a single
layer of clothing and chemical resistant gloves. 

Adhesives, Paint and Textiles: CMA preservative gloved data.  The dermal
UE is 0.135 mg/lb a.i. and the inhalation UE is 0.00346 mg/lb a.i.. The
values are based on 2 replicates where the test subjects were wearing a
single layer of clothing and chemical resistant gloves. Although this
unit exposure is based on minimal replicates, the exposure value is
similar to the one found in PHED for a similar scenarios.  

For the liquid pump scenarios, AD has recently developed definitions and
exposure methodology guidance when working with closed loading and
delivery systems in commercial and industrial settings.  Closed loading
systems are engineering controls that are “…designed to prevent
human exposure and should not require human intervention to eliminate
exposure” (CDPR 2003).  Closed transfer systems that require the
worker to open pour the concentrate into a transfer system are not
considered under this definition of closed loading systems because the
initial exposure for the open pour will require a quantitative
assessment.  Although closed loading and delivery systems are designed
to prevent or eliminate exposure, zero exposure is difficult to obtain. 
Even though analytical techniques can measure residues at extremely low
levels, for practical purposes at some point these residues can be
considered negligible or minimal.  To account for the fact that some
residues are available for dermal contact (and to a lesser degree
available for inhalation exposure), EPA is requiring that appropriate
PPE be worn by the worker.  

Negligible exposure can be considered to result from the use of systems
that are designed to drip less than 2 mL per coupling as in dry coupling
or metering pumps that are closed on both ends.  The second category,
minimal exposure, has been established because some closed systems are
not entirely enclosed or have not been engineered to reduce drips to 2
mL, but for practical purposes effectively reduce exposure such that
risks are not of concern.  Minimal exposure can be considered to result
from closed systems that are designed to prevent or eliminate inhalation
and dermal exposure but are not engineered to a specification (e.g.,
volume expected to be discharged).  

 

In the case of BNS, EPA expects that occupational exposures will be
negligible or minimal assuming that label-specified PPE (i.e.,
coveralls, long pants, long-sleeved shirts, and chemical resistant
gloves) and label-specified closed delivery and loading systems such as
dry coupling and closed system metering pumps are consistently utilized.
 Therefore, a quantitative exposure and risk assessment is not warranted
and the risks can be considered not a concern.

For roller/brush scenarios, the occupational PHED dermal and inhalation
unit exposure values for paintbrush applications (PHED scenario 22) were
used (single layer of clothing).  The inhalation exposure value is 0.28
mg/lb a.i. The dermal unit exposures are 180 mg/lb a.i. for ungloved
replicates and 24 mg/lb a.i. for gloved replicates. 

For airless sprayer scenarios, the occupational PHED dermal and
inhalation unit exposure values for airless sprayer application (PHED
scenario 23) were used (single layer of clothing). The inhalation
exposure value is 0.83 mg/lb a.i. The dermal unit exposures are 38 mg/lb
a.i. for ungloved replicates and 14 mg/lb a.i. for gloved replicates. 

Quantity handled/treated: The quantity handled/treated values were
estimated based on information from various sources.  The following
assumptions were made:

For the liquid pour scenarios, the quantity of the chemical that is
handled depends on the material that is being treated.  The following
values were used for the different materials:

Metalworking fluid:  2,502 lbs (approximately 300 gallons, based on the
density of water, 8.34 lb a.i./gal)  

Paint:  2,000 lbs (approximately 200 gallons, weight based on a density
10 lb a.i./gal) (standard AD assumption).	

Adhesives and Textiles:  10,000 lbs (standard AD assumption).

Drilling mud:  Up to 5 gallons of product are assumed to be open poured
in some instances before a metering system is employed.

For the roller/brush painting scenario, it was assumed that 50 lbs
(approximately 5 gallons of paint with a density of 10 lb/gal) of
treated paint are used (standard AD assumption).

For the airless sprayer in the painting scenario, it was assumed that
500 lbs (approximately 50 gallons of paint with a density of 10 lb/gal)
of treated paint are used. (standard AD assumption).

Duration of Exposure: The MOEs were calculated for the short- and
intermediate-term durations for occupational handlers using the
appropriate endpoints in Table 3.2.   

Exposure Calculations and Results

	The resulting inhalation and dermal exposures and MOEs for the
representative occupational handler scenarios are presented in Table
6.2. The calculated MOEs were above the target MOE of 100 for all
scenarios. 

Table 6.2.  Short- and Intermediate-Term Risks Associated with
Occupational Handlers

Exposure Scenario	

Method of Application

	

Unit Exposure

(mg/lb a.i.) 	Application Rate	Quantity Handled/ Treated per day	

Daily Dose (mg/kg/day)a	

MOEb 

(Target MOE = 100)

Inhalation 	Dermal 

	Inhalation 

	Dermal 

	Inhalation 

	Dermal 

  SEQ CHAPTER \h \r 1 Commercial, Institutional and Industrial Premises
and Equipment (Use Site Category III )

MWF	Liquid pour	0.00854	0.184	0.05% ai	300 gal (2,500 lbs)	0.00015
0.0033	240,000	15,000

Painting (commercial)	Paint brush	0.28	180	0.05% ai	5 gallons	0.0001
0.064	370,000	780

	Airless sprayer	0.83	38

50 gallons	0.003	0.14	12,000	270

Material Preservatives (Use Site Category VII)

Paint (manufacturing process)	Liquid pour	0.00346	0.135 (gloves)	0.05%
ai	2000 lbs	0.000049	0.0019	150,000	26,000

	Liquid pump	0.000403	0.454

10,000 lbs	0.000029	0.032	1.3E6	1,500

Industrial Processes and Water Systems (Use Site Category VIII)

Pulp and Paper	Metering pump	0.000265	0.00454

(gloves)	0.075 

lb ai/ton	500 tons	Closed loading systems are expected to result in
minimal exposure.  Specify closed loading system on label along with
long pants, long sleeved-shirts, and chemical resistant gloves.

Recirculating Cooling Water	Metering pump	0.000265	0.00454

(gloves)	5 ppm	5E7 gallons

	Once Through Cooling Water	Metering pump	0.000265	0.00454

(gloves)	9 ppm	2E6 to 5E8 gallons

	Packer Fluids and Drilling Muds	Pour liquid	0.45	10.1

(gloves)	200 ppm

(0.02% ai)	5 gallons

(41.7 lbs)	0.000054	0.0012	6.9E5	42,000

	Metering pump	0.000265	0.00454

(gloves)

Up to 420,000 gallons	See closed loading language above.

	

a	Absorbed Daily dose (mg/kg/day) = [unit exposure (mg/lb a.i.) x
absorption factor (1.0) x application rate x quantity treated / Body
weight (70 kg).

	b	MOE = NOAEL  (mg/kg/day) / Daily Dose [Where ST and IT inhalation
NOAEL = 37 mg/kg/day and ST and IT dermal NOAEL = 50 mg/kg/day].  Target
MOE = 100.

		6.2  	Occupational Post-application Exposures

	Occupational post-application dermal and inhalation exposures are
assumed to be negligible except for the machinist exposed to BNS-treated
metalworking fluids.  

Metalworking Fluids:  Machinist tc \l3 "6.2.2	Metal Working Fluids,
Machinist 

		There is a potential for dermal and inhalation exposure when a worker
handles treated metalworking fluids.  This route of exposure occurs
after the chemical has been incorporated into the metalworking fluid and
a machinist is using/handling this BNS treated end-product.

Dermal Exposures tc \l4 "6.2.2.1	   Dermal Risks 

Exposure Calculations 

	Short-, intermediate- and long-term exposure estimates were derived
using the 2-hand immersion model from ChemSTEER.  The model is available
at www.epa.gov/opptintr/exposure/docs/chemsteer.htm. The 2-hand
immersion equation is as follows: 

			PDR = SA x % a.i. x FT x FQ

	       				BW			

where: 

PDR	=	Potential dose rate (mg/kg/day);

SA		=	Surface area of both hands (cm2);

% a.i.	=	Fraction active ingredient in treated metalworking fluid
(unitless)

FT		=	Film thickness of metal fluid on hands (mg/cm2)

FQ		=	Frequency of events (event/day); 

BW	=	Body weight (kg)

Assumptions

The surface of area of both hands is 840 cm2 (USEPA 1997)

The body weight of an adult is 70 kg (USEPA 1997)

The percent active ingredient in treated metalworking fluid is 2000 ppm
of a 25% ai product or 500 ppm ai or 0.05 % ai (EPA Registration No.
464-686).

For short-, intermediate- and long-term durations, the film thickness on
the hands is 1.75 mg/cm2, which was extracted from the document
entitled, “A Laboratory Method to Determine the Retention of Liquids
on the Surface of Hands” (USEPA 1992).  The film thickness methodology
represents a machinist immersing both hands in metalworking fluid and
then partially cleaning hands with a rag. The film thickness was chosen
because the dermal endpoint for short-, intermediate- and long-term
durations is based on systemic effects.

Inhalation Exposures tc \l4 "6.2.2.2		Inhalation Risks 

Exposure Calculations 

	A screening-level intermediate and long term inhalation exposure
estimate for treated metalworking fluids has been developed using the
OSHA PEL for oil mist.  The equation used for calculating the inhalation
dose is:

PDR = PEL x IR x % a.i. x ED	

		   BW

where:

PDR		=	Potential dose rate (mg/kg/day);

PEL		=	OSHA PEL (mg/m3);

IR		=	Inhalation rate (m3 /hr)

% a.i.		=	Fraction active ingredient in treated metalworking fluid
(unitless) 

ED		=	Exposure duration (hrs/day); 

BW		=	Body weight (kg)

Assumptions  

		

The high-end oil mist concentration is based on OSHA’s Permissible
Exposure Limit (PEL) of 5 mg/m3 (NIOSH, 1998).

The percent active ingredient in treated metalworking fluid is 2000 ppm
of a 25% ai product or 500 ppm ai or 0.05 % ai (EPA Registration No.
464-686).

The inhalation rate for a machinist is 1.0 m3 /hr.

A machinist is exposed to the metalworking fluid 8 hours a day, for 5
days a week.

The body weight of an adult is 70 kg (USEPA 1997).

Dermal and Inhalation Results tc \l4 "6.2.2.2		Inhalation Risks 

	Table 6.3 shows the calculation of the absorbed daily dose and MOE for
a machinist working with metalworking fluids. The dermal and inhalation
MOE values are above the target MOE of 100 for all durations.  Although
the target inhalation MOE is 100, if the MOE is below 1,000 the Agency
may request a confirmatory inhalation toxicity study because the current
inhalation endpoint is based on an oral NOAEL.  Since the inhalation
MOEs are above 1,000, a confirmatory inhalation toxicity study is not
warranted based on the results of this scenario. 

Table 6.3.  Short-, Intermediate-, and Long-Term Risks Associated with
Postapplication Exposure to Metalworking Fluids treated with BNS
(Machinist)

% a.i.	Dermal Inputs	Inhalation Inputs	Absorbed Daily Dose (mg/kg/day)
MOE

	Hand Surface Area (cm2)	Film thickness (mg/cm2)	

Frequency (event/day)	OSHA PEL (mg/m3)	Inhal. rate 

(m3/hr)	Exposure Duration (hrs/day)	

Dermal a

	

Inhal. b 	

Dermal MOE 

(Target MOE = 100 for ST/IT and 300 for LT)c	Inhalation MOE 

(Target MOE = 100)d

	ST/IT/LT	ST/IT/LT

0.05	840	1.75	1	5	1.0	8	0.011	0.0004	4,800	93,000

a	Dermal Daily Dose (mg/kg/day) = [(% active ingredient * hand surface
area* dermal absorption factor (1)* film thickness (mg/cm2)* Frequency
(event/day)] / Body weight (70 kg).

b 	Inhalation Daily Dose (mg/kg/day) = % active ingredient * OSHA PEL
(mg/m3) * Inhalation rate (m3/hr) * exposure duration (hr/day) *
inhalation absorption factor (1)/ body weight (70 kg)

c  	Dermal MOE = NOAEL (mg/kg/day) / Daily Dose (mg/kg/day) [Where:
ST/IT/LT dermal NOAEL = 50 mg/kg/day; ST/IT target MOE = 100 and for LT
the target MOE = 300 ]. 

d	Inhalation MOE = NOAEL (mg/kg/day) / Daily Dose (mg/kg/day) [Where:
inhalation NOAEL = 37 mg/kg/day for all durations; target MOE = 100 for
all durations]

6.4	Data Limitations/Uncertainties tc \l2 "6.3	Data
Limitations/Uncertainties 

	There are several data limitations and uncertainties associated with
the occupational handler and post application exposure assessments. 
These include:

Surrogate dermal and inhalation unit exposure values were taken from the
proprietary Chemical Manufacturers Association (CMA) antimicrobial
exposure study (USEPA, 1999: DP Barcode D247642) or from the Pesticide
Handler Exposure Database (USEPA, 1998) (See Appendix B for summaries of
these data sources).   Since the CMA data are of poor quality, the
Agency requires that confirmatory data be submitted to support the
occupational scenarios assessed in this document.

The quantities handled/treated were estimated based on information from
various sources, including HED’s Standard Operating Procedures (SOPs)
for Residential Exposure Assessments (USEPA, 2000 and 2001), and
personal communication with experts.  In particular,   SEQ CHAPTER \h \r
1 the use information for the pulp and paper processing, drilling mud
uses, and cooling water tower uses are based on personal communication
with biocide manufacturers for these types of uses.  The individuals
contacted have experience in these operations and their estimates are
believed to be the best available without undertaking a statistical
survey of the uses.  In certain cases, no standard values were available
for some scenarios.  Assumptions for these scenarios were based on EPA
estimates and could be further refined from input from registrants.  

7.0	REFERENCES tc \l1 "7.0	REFERENCES 

American Chemical Council (ACC), 2005.  Slimicide Use in Papermaking
(Powerpoint Presentation).  ACC Biocides Council, September 17, 2003.

  SEQ CHAPTER \h \r 1 Freeman, N , Jimenez M, Reed KJ,Gurunathan S,
Edwards RD, Roy A, Adgate JL, Pellizzari ED, Quackenboss J, Sexton K,
Lioy PJ, 2001.  Quantitative analysis of chilren’s microactivity
patterns:  The Minnesota Children’s Pesticide Exposure Study.  Journal
of Exposure Analysis and Environmental Epidemiology.  11(6): 501-509.

USEPA. 1992.  A Laboratory Method to Determine the Retention of Liquids
on the Surface of Hands, Exposure Evaluation Division, Office of
Pollution Prevention and Toxic, USEPA, EPA 747-R-92-003, September,
1992.

USEPA. 1996.  Office of Research and Development, Descriptive Statistics
Tables from a Detailed Analysis of the National Human Activity Pattern
(NHAPS) Data; EPA/600/R-96/148, July 1996.   Data Collection Period
October 1992 - September 1994 . 

USEPA.  1997.  Exposure Factors Handbook. Volume I-II.  Office of
Research and Development.  Washington, D.C.  EPA/600/P-95/002Fa. August
1997.

USEPA. 1998. PHED Surrogate Exposure Guide. Estimates of Worker Exposure
from the Pesticide Handler Exposure Database Version 1.1.   Washington,
DC:  U.S. Environmental Protection Agency.

  SEQ CHAPTER \h \r 1 USEPA. 1999.  Evaluation of Chemical Manufacturers
Association Antimicrobial Exposure Assessment Study (Amended on 8
December 1992).  Memorandum from Siroos Mostaghimi, PH.D., USEPA to
Julie Fairfax, USEPA. Dated November, 4 1999.  DP Barcode D247642.

USEPA.  2000.  Residential SOPs.  EPA Office of Pesticide Programs,
Human Health Effects Division. Dated April 5, 2000.

USEPA.  2001.  HED Science Advisory Council for Exposure. Policy Update,
November 12.  Recommended Revisions to the Standard Operating Procedures
(SOPs) for Residential Exposure Assessment, February 22, 2001. 

APPENDIX A: Summary of CMA and PHED Data

 tc \l1 "APPENDIX A: Summary of CMA data and PHED Chemical
Manufacturers Association (CMA) Data:

In response to an EPA Data Call-In Notice, a study was undertaken by the
Institute of Agricultural Medicine and Occupational Health of The
University of Iowa under contract to the Chemical Manufacturers
Association.  In order to meet the requirements of Subdivision U of the
Pesticide Assessment Guidelines (superseded by Series 875.1000-875.1600
of the Pesticide Assessment Guidelines), handler exposure data are
required from the chemical manufacturer specifically registering the
antimicrobial pesticide.   The applicator exposure study must comply
with the assessment guidelines for Applicator Exposure Monitoring in
Subdivision U and the Occupational and Residential Exposure Test
Guidelines in Series 875.  For this purpose, CMA submitted a study on 28
February, 1990, entitled "Antimicrobial Exposure Assessment Study
(amended on December 8, 1992)" which was conducted by William Popendorf,
et al.  It was evaluated and accepted by Occupational and Residential
Exposure Branch (OREB) of Health Effect Division (HED), Office of
Pesticides Program (OPP) of EPA in 1990.  The purpose of this CMA study
was to characterize exposure to antimicrobial chemicals in order to
support pesticide reregistrations (CMA, 1992).  The unit exposure values
presented in the most recent EPA evaluation of the CMA database (USEPA,
1999b) were used in this assessment.

The advantages of CMA data over other surrogate data sets is that the
chemicals and the job functions of mixer/loader/applicator were defined
based on common application methods used for antimicrobial pesticides. 
A few of the deficiencies in the CMA data are noted below:

The inhalation concentrations were typically below the detection limits,
so the unit exposure values for the inhalation exposure route could not
be accurately calculated. 

QA/QC problems in the study included a lack of or low recovery of
either/or field fortification, laboratory recoveries, and storage
stability information.

Data have an insufficient amount of replicates.

The Pesticide Handlers Exposure Database (PHED):

The Pesticide Handlers Exposure Database (PHED) has been developed by a
Task Force consisting of representatives from Health Canada, the U.S.
Environmental Protection Agency (EPA), and the American Crop Protection
Association (ACPA).  PHED provides generic pesticide worker (i.e.,
mixer/loader and applicator) exposure estimates.  The dermal and
inhalation exposure estimates generated by PHED are based on actual
field monitoring data, which are reported generically (i.e., chemical
specific names not reported) in PHED.  It has been the Agency’s policy
to use surrogate or generic exposure data for pesticide applicators in
certain circumstances because it is believed that the physical
parameters (e.g., packaging type) or application technique (e.g.,
aerosol can), not the chemical properties of the pesticide, attribute to
exposure levels. [Note: Vapor pressures for the chemicals in PHED are in
the range of E-5 to E-7 mm Hg.]  Chemical specific properties are
accounted for by correcting the exposure data for study specific field
and laboratory recovery values as specified by the PHED grading
criteria.

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PHED handler exposure data are generally provided on a normalized basis
for use in exposure assessments.  The most common method for normalizing
exposure is by pounds of active ingredient (ai) handled per replicate
(i.e., exposure in mg per replicate is divided by the amount of ai
handled in that particular replicate).  These unit exposures are
expressed as mg/lb ai handled.  This normalization method presumes that
dermal and inhalation exposures are linear based on the amount of active
ingredient handled.

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