REVISED DRAFT

Tributlytin-containing Compounds

Tributyltin oxide (TBTO)

Tributyltin benzoate (TBTB)

Tributyltin maleate (TBTM)

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 26, 2008

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  5  

  HYPERLINK \l "_Toc125183617"  1.1	Purpose	  PAGEREF _Toc125183617 \h 
5  

  HYPERLINK \l "_Toc125183618"  1.2	Criteria for Conducting Exposure
Assessments	  PAGEREF _Toc125183618 \h  5  

  HYPERLINK \l "_Toc125183619"  1.3	Chemical Identification	  PAGEREF
_Toc125183619 \h  7  

  HYPERLINK \l "_Toc125183620"  1.4	Physical/Chemical Properties	 
PAGEREF _Toc125183620 \h  7  

  HYPERLINK \l "_Toc125183621"  2.0	 USE INFORMATION	  PAGEREF
_Toc125183621 \h  8  

  HYPERLINK \l "_Toc125183622"  2.1	 Formulation Types and Percent
Active Ingredient	  PAGEREF _Toc125183622 \h  8  

  HYPERLINK \l "_Toc125183623"  2.2	 Summary of Use Pattern and
Formulations	  PAGEREF _Toc125183623 \h  8  

  HYPERLINK \l "_Toc125183624"  3.0	SUMMARY OF TOXICITY DATA	  PAGEREF
_Toc125183624 \h  9  

  HYPERLINK \l "_Toc125183625"  3.1	Acute Toxicity	  PAGEREF
_Toc125183625 \h  9  

  HYPERLINK \l "_Toc125183626"  3.2	Summary of Toxicity Endpoints	 
PAGEREF _Toc125183626 \h  10  

  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  13  

  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

	4.2.2.2
Mattresses……………………………………………………
…………………………………19

         4.2.3    	Data
Limitations/Uncertainties………………………………………
………………………..22

  HYPERLINK \l "_Toc125183633"  5.0	RESIDENTIAL AGGREGATE RISK
ASSESSMENT AND CHARACTERIZATION 	  PAGEREF _Toc125183633 \h  24  

  HYPERLINK \l "_Toc125183634"  6.0	OCCUPATIONAL EXPOSURE ASSESSMENT	 
PAGEREF _Toc125183634 \h  24  

  HYPERLINK \l "_Toc125183635"  6.1 	Occupational Handler Exposures	 
PAGEREF _Toc125183635 \h  26  

  HYPERLINK \l "_Toc125183636"  6.2  	Occupational Post-application
Exposures	  PAGEREF _Toc125183636 \h  31  

  HYPERLINK \l "_Toc125183642"  6.4	Data Limitations/Uncertainties	 
PAGEREF _Toc125183642 \h  35  

  HYPERLINK \l "_Toc125183643"  7.0	REFERENCES	  PAGEREF _Toc125183643
\h  36  

  HYPERLINK \l "_Toc125183645"  APPENDIX A: Summary of CMA and PHED Data
  PAGEREF _Toc125183645 \h  37  

  HYPERLINK \l "_Toc125183645"  APPENDIX B: MCCEM Output
(Fogging)………………………………………………………
……………….  PAGEREF _Toc125183645 \h  37  

 

EXECUTIVE SUMMARY 

	This document is the Occupational and Residential Exposure Chapter of
the Reregistration Eligibility Decision (RED) document for the
tributlytin (TBT)-containing compounds including tributyltin oxide
(TBTO), tributyltin benzoate (TBTB), and tributyltin maleate (TBTM). It
addresses the potential risks to humans that result from its direct use
in occupational settings and resulting treated articles in residential
settings.  

	TBT is used as a bacteriostat, microbicide/microbistat, fungicide,
slimicide, algaecide, antifoulant, virucide, disinfectant, sanitizer,
miticide, and insecticide.  TBT is formulated as a soluble concentrate.
TBT concentrations in products range from 0.3 to 53 percent (i.e.,
74489-1). The product is used in the following use categories: 
agricultural premises, commercial/ institutional/industrial premises and
equipment, material preservatives, industrial processes and water
systems, antifouling coatings, and wood preservations (i.e.,
stains/water sealants).  Examples of uses for TBT in these settings
include its use by residential and commercial painters (as a wood
preservative), as a material preservative incorporated into textiles,
metalworking fluids, oilfield injection systems, laundry additive, sonar
domes, and in industrial process water systems such as pulp and paper
mills, cooling tower water (recirculating 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
oral, dermal, and inhalation endpoints for all durations (ST/IT/LT
durations) are based on the same study.  The BMD10 (bench mark dose) of
0.03 mg/kg/day (NOAEL of 0.025 mg/kg/day and LOAEL of 0.25 mg/kg/day) is
used for all durations.  The adverse effect for this endpoint is based
on immunosupression.  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 TBT inhalation,
dermal, and 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 10x special sensitivity factor is applied to
the non occupational population.    

		This occupational and residential assessment was based on examination
of the product labels that describe the uses.  It has been determined
that there are residential products of TBT that are applied directly
(e.g., wood stain preservative) as well as an in-can preservative use
(e.g., laundry additive 10466-24).  Occupational handlers may be exposed
in the manufacturing of other products (e.g., textiles), during
treatment of water systems, agricultural poultry, farm premise
applications, commercial painters, and metalworking fluids (MWF). 
Post-application exposures are likely to occur in residential settings
by contacting treated articles such as clothing or in occupational
settings such as reentry into poultry/animal premises. The
representative scenarios selected by EPA for assessment were evaluated
using maximum application rates as stated on the product labels.  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., staining with a paint brush and/or
airless sprayer are considered to be intermittent in nature).  The
short-term dermal MOEs for the paint brush and airless sprayer are both
< 1, and therefore, the risks are of concern.  The residential target
MOE is 1000.

Inhalation

		For the residential painting inhalation assessment, the inhalation
MOEs were less than 1 which is below the target MOE of 1000 for the
brush and airless application techniques, and therefore, are of concern.

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 are of concern using the transfer residue study developed
for a screening-level assessment (i.e., toddler dermal MOE = 35).  A
second residue transfer study was conducted to refine the transfer of
residues.  This study determined the residues to be <10 ppb.  However,
there is insufficient information available in the study to assume that
a reasonable certainty of no harm would occur from a child exposed to
TBTO-treated fabric using the revised methodology.  In addition, the
incidental oral exposures from children mouthing treated fabric is of
concern (oral MOE = 2).  Furthermore, the dermal MOEs are also of
concern for dermal contact on TBT-treated mattresses (MOE is 8 for
children when using the transfer residue data from the first residue
transfer study). 

Inhalation 

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

Occupational Handler Risk Summary

	In summary, for the non fogging agricultural uses the inhalation MOEs
are greater than 100, and therefore not of concern.  Some of the dermal
MOEs for the same scenarios are above and some below the target MOE of
100.  However, the use of chemical resistant gloves was not assessed for
all scenarios because the data were not available.  Based on the low
application rate (i.e., 0.00033 lb ai/gallon), the magnitude of the
MOEs, and assuming that chemical resistant gloves would afford
substantial reduction in exposure, these dermal MOEs do not appear to be
of concern if gloves are required on the labels (confirmatory data would
be required).  The MOEs for the material preservative use are below the
target MOE of 100.  Potential mitigation for material preservative
additives would be to require closed loading systems.  The industrial
process and water system uses also need to be restricted to closed
loading systems.  At this time, it is unclear how the antifouling
coatings are applied and additional information on the application
techniques are requested.  Finally, the commercial applications of
stains indicate MOEs of concern (i.e., MOEs less than 1).

Occupational Post Application/Bystander Risk Summary

	Based on the application methods, inhalation post-application exposures
are expected to be minimal except for the machinist using TBT-treated
cutting fluids.  The dermal and inhalation MOEs for machinists are 3 and
36, respectively.  The risks are of concern for the machinist.

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 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. 

  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 TBT-containing compounds (TBTO,
TBTB, TBTM), case number 2620. The information presented in this
Occupational and Residential Exposure chapter is for use in EPA's
development of the TBT 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 TBT, both criteria are met. Toxicological
endpoints were selected for short-, intermediate-, and long-term dermal,
inhalation, and incidental oral exposures to TBT. 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 TBT 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 TBT products have 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 TBT
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

		

		Molecular structures for tributlytin-containing compounds are
illustrated in Figure 1. 

			Figure 1.  Molecular Structures of TBTO, TBTB, and TBTM,
respectively.

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

		Table 1.2 shows physical/chemical characteristics that have been
reported for TBT (TBT Product Chemistry Chapter).

Table 1.2.  Physical/Chemical Properties of TBT





Parameter	

TBTO	TBTB	TBTM 



Molecular Weight (g/mol)	596	411	405.13



Half life in air	0.125 days	0.241 days	2.5 hrs



˚C)	417	390	415



Water Solubility (mg/L)	0.0896	0.257	4.086



Vapor Pressure (mm Hg at 25 ˚C)	7.8E-6	1.34E-6	1.74E-7

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 

		TBT is used as a bacteriostat, microbicide/microbistat, fungicide,
slimicide, algaecide, antifoulant, virucide, disinfectant, sanitizer,
miticide, and insecticide.  TBT is formulated as a soluble concentrate.
TBT concentrations in products range from 0.3 to 53 percent (i.e.,
74489-1). 

 

		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) was identified based on a review of the TBT
product labels: 

(I) Agricultural premises and equipment; 

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

(VII)   SEQ CHAPTER \h \r 1 Material preservatives;

(VIII) Industrial processes and water systems;

(IX) Antifouling coatings; and 

(X)  Wood preservatives.

	Specific uses within these use categories are identified in Table 2.1. 
From Table 2.1, EPA has selected representative exposure scenarios to
assess TBT 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 TBT. 

Use Site Category	Example Use Sites	Scenarios

Use Site Category I

Agricultural premises and equipment



Use Site Category III

Commercial, institutional and industrial premises and equipment

Polymers 



Use Site Category VII

Material Preservatives	Used in the production of various household,
institutional and industrial items	Addition to products during
manufacture, including:

Polymers 



Use Site Category VIII

Industrial processes and water systems	Used on fresh water supplies for
commercial and industrial systems	Addition to water for recirculating
cooling towers



Use Site Category 

Antifoulant coatings



Use Site Category 

Wood preservatives	Used in preservation of  wood products

	

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 TBT are summarized below in Table 3.1. The
acute toxicity database for the tributyltin compounds is considered
incomplete; the battery of acute toxicity studies required for labeling
purposes has not been submitted by the registrants for each of the
tributyltin compounds (tributyltin oxide, tributyltin maleate and
tributyltin benzoate) grouped in this hazard assessment.  The available
data does show that exposure to tributyltin oxide and tributyltin
maleate can result in severe oral and dermal toxicities (Toxicity
Category II). However, tributyltin oxide and tributyltin maleate are not
dermal sensitizers.  Dermal and oral exposures to tributyltin benzoate
can potentially cause moderate (Toxicity category III) to severe
(Toxicity category II) toxicities, respectively. 

Table 3.1. Acute Toxicity Profile for Technical (95.0- 97.5 % a.i.)
Tributyltin Compounds

Guideline Number	Study Type	MRID Number	Results	Toxicity Category

Tributyltin Oxide

870.1100

(§ 81-1)	Acute Oral – Rat 

	00085004,

92172013	LD50 =180 mg/kg (males)

LD50 =150 mg/kg (females)

LD50 =170 mg/kg (combined)	II

870.1100

(§ 81-1)	Acute Oral – Rat

	00085003,

92172004	LD50 =193 mg/kg (males)

LD50 =123 mg/kg (females)

LD50 =160 mg/kg (combined)	II

870.2600

(§ 81-6)	Skin Sensitization –Guinea pigs

	00104789, 92172014	Non sensitizer	Not applicable

Tributyltin Maleate

870.1100

(§ 81-1)	Acute Oral – Rat 

	43851201	LD50 = 224.7 mg/kg	II

870.2600

(§ 81-6)	Skin Sensitization – Guinea pigs

	44142303	Non sensitizer. Not sensitizing; minimal irritation in
response to induction, but no increase in response to challenge dose	Not
applicable

Tributyltin Benzoate

870.1100

(§ 81-1)	Acute Oral – rat

Purity 

	42415801	LD50 =115 mg/kg (males)

LD50 =115 mg/kg (females)

LD50 =115 mg/kg (combined)	II

870.1200

(§ 81-2)	Acute Dermal – rat

Purity 

	42415802	LD50  > 2000 mg/kg (combined)	III

870.2500

(§ 81-5)	Primary Dermal Irritation – rabbit

Purity 

	42415803	Severe Irritation	I



	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 TBT.

  SEQ CHAPTER \h \r 1 Exposure

Scenario	Dose Used in Risk Assessment

(mg/kg/day) 	Special Sensitivity*, UF, Target MOE, 

for Risk Assessment	Study and Toxicological Effects

Dietary Risk Assessments

Acute Dietary

(females 13-49 and general population)	No appropriate endpoints were
identified in the oral toxicity studies that represent a single dose
effect for the general population and females 13-49.  In addition, the
current use patterns for the tributyltin-containing chemicals do not
indicate the potential for direct or indirect dietary exposures. 
Therefore, an acute dietary risk assessment is not required. 

Chronic Dietary

(all populations)	BMD10 =  0.03 mg/kg/day based on immunosupression
(established by EPA/IRIS and used to estimate their oral RfD of 0.0003
mg/kg/day). 

	Special Sensitivity = 10

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

 

Chronic RfD (cRfD) =  0.00003 mg/kg/day

Although the current use patterns for the tributyltin-containing
chemicals do not indicate the potential for chronic dietary exposures,
this endpoint is selected for future reference.  A chronic dietary risk
assessment is not required at this time. 	Open Literature Study

Vos et al., (1990) Immunotoxicity of bis(tri-n-butyltin)oxide in the
rat: Effects on thymus-dependent immunity and on nonspecific resistance
following long-term exposure in young vs aged rats.  Toxicol. Appl.
Pharmacol.  105:144-155.

 

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers
and increase in T. spiralis larvae in muscle) following 4 months and
16.5 months of exposure to Tributyl Tin Oxide.  (Review by EPA/IRIS,
1997). 

Non-Dietary Risk Assessments

Incidental Oral Short-Term 

(1-30 days) and Intermediate-Term  (1- 6 months) 

	BMD10 =  0.03 mg/kg/day based on immunosupression (established by
EPA/IRIS and used to estimate their oral RfD of 0.0003 mg/kg/day). 

	Special Sensitivity = 10

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

Target MOE = 1000	Open Literature Study

Vos et al., (1990) Immunotoxicity of bis(tri-n-butyltin)oxide in the
rat: Effects on thymus-dependent immunity and on nonspecific resistance
following long-term exposure in young vs aged rats.  Toxicol. Appl.
Pharmacol.  105:144-155.

 

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers
and increase in T. spiralis larvae in muscle) following 4 months and
16.5 months of exposure to Tributyl Tin Oxide.  (Review by EPA/IRIS,
1997). 

Dermal

(all durations)	BMD10 =  0.03 mg/kg/day based on immunosupression
(established by EPA/IRIS and used to estimate their oral RfD of 0.0003
mg/kg/day). 

	Special Sensitivity = 10

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

Target MOE occ. = 100

Target MOE res. = 1000	Open Literature Study

Vos et al., (1990) Immunotoxicity of bis(tri-n-butyltin)oxide in the
rat: Effects on thymus-dependent immunity and on nonspecific resistance
following long-term exposure in young vs aged rats.  Toxicol. Appl.
Pharmacol.  105:144-155.

 

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers
and increase in T. spiralis larvae in muscle) following 4 months and
16.5 months of exposure to Tributyl Tin Oxide.  (Review by EPA/IRIS,
1997). 

Inhalation

(all durations)	BMD10 =  0.03 mg/kg/day based on immunosupression
(established by EPA/IRIS and used to estimate their oral RfD of 0.0003
mg/kg/day). 

	Special Sensitivity = 10

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

Target MOE occ. = 100

Target MOE res. = 1000	Open Literature Study

Vos et al., (1990) Immunotoxicity of bis(tri-n-butyltin)oxide in the
rat: Effects on thymus-dependent immunity and on nonspecific resistance
following long-term exposure in young vs aged rats.  Toxicol. Appl.
Pharmacol.  105:144-155.

 

NOAEL = 0.025 mg/kg/day

LOAEL = 0.25 mg/kg/day based on immunotoxicity (depression of IgE titers
and increase in T. spiralis larvae in muscle) following 4 months and
16.5 months of exposure to Tributyl Tin Oxide.  (Review by EPA/IRIS,
1997). 

Dermal Absorption	Although there is no guideline dermal toxicity study
(range-finding study only) and no acceptable dermal absorption study
(75% recovery of 113Sn-tributyltin oxide), a 15% dermal absorption
factor for tributyltin oxide has been used (EPA/HED) for route-to-route
extrapolation.   

UF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL
= lowest observed adverse effect level, RfD = reference dose, MOE =
margin of exposure, NA = Not Applicable

 *The Special Sensitivity factor is applied to a selected dose if there
is evidence of increased susceptibility to children from non-dietary
exposures to pesticides.  Several published literature show that
tributyltin oxide causes depression of immune functions dependent on the
thymus, particularly in young animals.  This is a critical effect that
occurs at doses lower than those causing other toxicities.  Therefore,
application of this factor provides adequate protection to the most
sensitive population, 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 

	There are registered products containing TBT that can come in contact
with adults and/or children.  For example, there are TBT products that
can be applied directly by the homeowner.  The consumer products include
EPA Reg. Nos. 577-539, 577-544, 1022-511, 7313-6, 8177-71,  9339-14 that
are for preserving wood such as siding, shingles, fences, decks,
millwork, etc.  Articles treated with TBT in occupational settings may
also have the potential for post-application residential exposure.  For
example, there are TBT treated articles such as textiles including
mattress pads, ticking, and covers.  Additionally, there are labels such
as 3090-123 listing textile treatments with restrictions for no food
contact or diapers.  However, there are no other clothing restrictions,
and therefore, it is assumed clothing worn by adults and/or children can
be treated. 

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

	The exposure scenarios assessed in this document for the representative
uses of TBT 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 wood preservative use. 
Post-application dermal, inhalation, and/or incidental ingestion
exposures are assessed for treated articles including clothing and
mattress.  Post-application/bystander inhalation exposures are expected
to be minimal for most uses, except for drift occurring during 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
TBT.

Representative Use	Application Method	Exposure Scenario	Example
Registration Number	Application Rate

Wood Preservative	Brush and airless sprayer

(Note:  dip not assessed separately)	ST Handler:  adult dermal and
inhalation.	1022-511

(577-539, 577-544, 1022-511, 7313-6, 8177-71)	0.062 lb ai/gallon

[8.3 lbs per gal density x 0.75% ai   = 0.062 lb ai/gallon of stain]

Textiles (a)

(exposures to treated  articles are represented by exposure to clothing
and mattress)	NAa	ST Post-app: wearing treated clothing, adult dermal;
child incidental ingestion and dermal 

ST Post-appl: Sleeping on treated mattress; adult dermal and child
incidental ingestion and dermal	3090-123

(textile)

10466-24

(mattress)	0.05% ai or 500 ppm TBT

[1% pesticide product by weight of material treated x 5% ai in
formulated product = weight fraction of 0.0005 ai or 0.05% ai or 500
ppm]

0.056% ai or 560 ppm TBT

[3.5% formulated product by weight of goods x 1.6% ai in formulated
product = weight fraction of 0.00056 ai or 0.056% ai or 560 ppm]

(a)    The handlers scenarios for textiles 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 data and the equations in Section 1.2, “Criteria
for Conducting Risk Assessment.”  A summary of the PHED data 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)

    

For the airless sprayer scenario, measured PHED dermal and inhalation
unit exposure values for a residential handler applying a pesticide
using an airless sprayer to stain the siding of a residential home were
used as a surrogate for this scenario.  These unit ungloved exposure
values (79 mg/lb a.i. for dermal and 0.83 mg/lb a.i. for inhalation)
represent a handler wearing short pants and a short sleeve shirt, with
no gloves. 

For the brush/roller scenario, measured PHED dermal and inhalation unit
exposure values for a residential handler applying a pesticide using a
paint brush to the interior of a bathroom were used as a surrogate for
this scenario.  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 stain 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 stain will be used. 
This is based on the coverage of approximately 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 TBT 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 and dermal MOEs are below the target
MOE of 1000 for all scenarios.  Therefore, the risks exceed EPA’s
level of concern.  

Table 4.2 TBT 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 = 1000)





Inhalation	Dermal	Inhalation	Dermal	Inhalation	Dermal

Staining/

Painting	Paint brush	0.062 lb ai/gal

	2 gallons	0.28	230	5E-4	0.061	60	<1

	Airless sprayer

15 gallons	0.83	79	0.011	0.16	3	<1

a	Application rates are the maximum application rates determined from
EPA registered label for TBT (i.e., 0.75% ai in EPA Reg. No. 1022-99;
next highest rate is 0.5% ai).

b	Amount handled per day values are estimated.	

c	Daily dose (mg/kg/day) = [unit exposure (mg/lb a.i.) x application
rate (lb ai/gal) x quantity treated (gal/day) x absorption factor (100%
for inhalation and 15% dermal)]/ Body weight (70 kg).

d	MOE = NOAEL / Daily Dose.  [Where short-term inhalation and dermal
BMD10 = 0.03 mg/kg/day]. Target MOEs = 1000.

	

 	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 and sleeping on
mattresses (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 during manufacturing with TBT as a preservative
(i.e., bacteriostatic/fungistatic).  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 TBT 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 TBT treated textiles.  Nonetheless, the short-term dermal
toxicological endpoint is protective of the intermediate- and long-term
durations because the same endpoint value is used to assess all
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 high1% by weight of the
textiles and the formulated product itself is 5% ai (1% formulated
product by weight of textile x 5% ai = 0.0005 weight fraction or 0.05%
ai in textiles or 500 ppm TBT in textiles).

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 initially 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.  In
this revised assessment, two mattress ticking leaching studies were
submitted for TBTO.  Although these studies used mattress ticking, not
clothing, it does provide measured residues transferred from a fabric. 
In the first study (Thomson Research Associates Report No.
RG-2002-03-01), Ultra-Fresh 300DN was applied at 2.58% formulated
product (1 % TBTO in product) to the mattress ticking.  Exposure was
simulated using an artificial sweat solution applied to a piece of
poly/cotton fabric, weighted, and rolled over the treated mattress
ticking 350, 700, and 1,400 times to simulate exposure for 1, 2, and 4
weeks, respectively.  This simulated 50 movements per night for an
individual.  The results of this study indicated up to 0.41 ug/cm2 was
transferred from the mattress ticking when simulated for 4 weeks. 
Therefore, the amount available on a daily basis is 0.41 ug/cm2 / 28
days = 0.015 ug/cm2.  A second study (Thomson Research Associates Report
No. RG-2004-03-01) applied 1.72% formulated product (1 % TBTO in
product) and monitored the residue transfer using a less abrasive
monitoring technique.  The second study indicated no leaching of TBTO
residues (LOD = 10 ppb).  Insufficient information was available in the
second study to calculate the amount of TBTO in ug/cm2 transferred from
the mattress ticking (i.e., weight of material not provided to convert
the 10 ppb concentration to ug/cm2).  Therefore, MOEs at ½ LOD are not
presented.  The first study was designed to simulate the
“worst-case” of residue transfer as a screening-level assessment. 
The methodology for the “worst-case” scenario was then refined to
attempt to develop a “reasonable worst-case”.  However, neither
method provided information linking residue transfer to actual human
exposure.  The first study appears to be representative of the high end
residue transfer to be used as a screening-level assessment.  But there
is insufficient information available in the second study to assume that
a reasonable certainty of no harm would occur from a child exposed to
TBTO-treated fabric using the methodology of the second study.  This
revised TBT assessment would have provided a range of risks from these
two studies if the LOD of 100 ppb could be converted to ug/cm2. 
Nonetheless, the second study can not be confirmed as being designed to
represent a reasonable certainty of no harm and the incidental oral
component of the treated clothing would still be the risk driver for
this use on textiles.  Note:  The application rates in these studies
(i.e., 2.58% and 1.72% by weight product containing 1% TBTO) are less
then the maximum labeled rate for TBTO (i.e., 5% product by weight
containing 1% TBTO).

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 short-term dermal doses and MOEs for adults and
toddlers wearing treated clothing are shown in Table 4.3.  The dermal
MOEs for adults and toddlers are less than the target MOE of 1000
assuming a 100% and 5% residue transfer factors and the results of one
of the two TBTO leaching studies.  Note:  A second study indicated that
the residue transfer was less then 10 ppb; however there is insufficient
information in the study to convert the 10 ppb to ug/cm2 and it is not
possible to determine if the second study is representative of a high
end exposure potential.  Therefore, the risks are of concern.  

Table 4.3:  Dermal Post-application Exposures and MOEs for Toddlers and
Adults Contacting Treated Clothing

Exposure Scenario	Weight of clothing worn (g/day)a	Surface Area Exposed

(cm2)	Measured Residue

(ug/cm2)	Percent residue transferred from clothing to skin (%)	Daily
doseb  

(mg a.i./ kg/day)	Dermal MOEc (Target MOE=1000)

Maximum Labeled Rate:  5% product by weight (product containing 1% TBTO)

Toddler	56.7	5,670	NA	100	0.284	<1





5	0.0142	2

Adult	169	16,900	NA	100	0.181	<1





5	0.0091	3

Study #1 Application Rate:  2.58% product by weight (product containing
1% TBTO)

Toddler	NA	5,670	0.015	NA	0.00085	35

Study #2 Application Rate:  1.72% product by weight (product containing
1% TBTO)

Toddler	NA	5,670	<10 ppb	NA	Need more information to convert LOD of 10
ppb to ug/cm2



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, 0.15) * (conversion factor, 1000 mg/g)] / (body
weight, 15 kg child and 70 kg adult). – or --   Absorbed daily dose
(mg/kg/day) = Surface area exposed (cm2) x measured residue (ug/cm2) x
15% dermal abs x unit conversion ug to mg (1/1000) x (1/15 kg child BW).


c. 	Dermal MOE = BMD10 (mg/kg/day) / Daily Dose [Where dermal BMD10  =
0.03 mg/kg/day].  Target MOE = 1000.

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 TBT.

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									

where:

C		=	concentration on clothing (mg/cm2);

% applied	= 	percent of product applied (%);

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

W 		= 	weight of clothing (mg/cm2).

Assumptions

The formulated product is applied at rates as high1% by weight of the
textiles and the formulated product itself is 5% ai (1% formulated
product by weight of textile x 5% ai = 0.0005 weight fraction or 0.05%
ai in textiles or 500 ppm TBT in textiles).

 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 4.4 shows the calculation of the short- and intermediate-term
oral dose and oral MOE for toddlers mouthing treated textiles. The MOE
value is less than target MOE of 1000 for the maximum concentration
allowed on the label (MOE is ).  

Table 4.4:  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 =1000)

0.01	1%	0.005	100	50	0.017	2



a.	Concentration on clothing (mg/cm2) = (5 percent a.i. in product, %) /
100 * (1 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 = BMD10  (mg/kg/day) / Potential Daily Dose [Where short-
and intermediate-term incidental oral  BMD10= 0.03 mg/kg/day].  Target
MOE = 1000.	

Note:  The dermal and incidental oral exposure occurring from textiles
should also be reported as a total exposure (i.e., dermal and oral
combined) because of the same toxicological effect is used for both
routes of exposure.  However, the two routes of exposure were not
combined at this time because the risks are of concern individually.

 

4.2.2.2	Mattresses tc \l4 "4.4.2.2	Mattresses 

	Mattress pads, ticking, and mattress covers can be treated with TBT
during the manufacturing process.  Therefore post application dermal
exposures to treated mattresses may occur.  It was assumed that exposure
to a textile mattress cover will represent exposure to all other
mattress components.  Since the mattress cover is actually impregnated
with TBT both short- and intermediate-term exposures durations were
assessed.

Dermal Exposure to Treated Mattress Covers

Exposure Calculations	

	Short- and Intermediate-term exposures - There the potential for short-
and intermediate-term exposures leading to systemic effects when adults
and children come into contact with mattress covers treated with TBT,
through the regular use of the mattress.  Dermal exposures and MOEs were
calculated for children and adults contacting treated mattresses in
residential homes.  To determine short and intermediate-term exposures
to TBT in mattresses, the following equation was used:

PDD = D x WF1 x WF2 x PF x SA x DA

                                 BW

where:

PDD 	= 	Potential daily dose (mg/kg/day)

D	= 	Mattress textile weight density (mg/cm2)

WF1 	= 	Weight fraction of TBT in the mattress cover (%)

WF2 	= 	Weight fraction of TBT transferred from the mattress cover to
skin (cover)

PF	=	Protection factor from single layer of clothing/sheet (%)

SA 	= 	Body surface area contacting mattress (cm2/day)

DA	=	Dermal absorption (%)

BW 	= 	Body weight (kg)

Assumptions

Mattress covers are treated at the rate of 3.5% formulated product by
weight of goods x 1.6% ai in formulated product = weight fraction of
0.00056 ai or 0.056% ai or 560 ppm (EPA Reg. No. 10466-24).

The mattress cover density is assumed to be 10 mg/cm2 based on the
density of mixed cotton and synthetics (HERA 2003). 

In the initial TBT assessment, default residue transfer factors of 100%
and 5% were used.  In this revised assessment, two mattress ticking
leaching studies were submitted for TBTO.  In the first study (Thomson
Research Associates Report No. RG-2002-03-01), Ultra-Fresh 300DN was
applied at 2.58% formulated product (1 % TBTO in product) to the
mattress ticking.  Exposure was simulated using an artificial sweat
solution applied to a piece of poly/cotton fabric, weighted, and rolled
over the treated mattress ticking 350, 700, and 1,400 times to simulate
exposure for 1, 2, and 4 weeks, respectively.  This simulated 50
movements per night for an individual.  The results of this study
indicated up to 0.41 ug/cm2 was transferred from the mattress ticking
when simulated for 4 weeks.  Therefore, the amount available on a daily
basis is 0.41 ug/cm2 / 28 days = 0.015 ug/cm2.  A second study (Thomson
Research Associates Report No. RG-2004-03-01) applied 1.72% formulated
product (1 % TBTO in product) and monitored the residue transfer using a
less abrasive monitoring technique.  The second study indicated no
leaching of TBTO residues (LOD = 10 ppb).  Insufficient information was
available in the second study to calculate the amount of TBTO in ug/cm2
transferred from the mattress ticking (i.e., weight of material not
provided to convert the 10 ppb concentration to ug/cm2).  Therefore,
MOEs at ½ LOD are not presented.  The first study was designed to
simulate the “worst-case” of residue transfer as a screening-level
assessment.  The methodology for the “worst-case” scenario was then
refined to attempt to develop a “reasonable worst-case”.  However,
neither method provided information linking residue transfer to actual
human exposure.  The first study appears to be representative of the
high end residue transfer to be used as a screening-level assessment. 
But there is insufficient information available in the second study to
assume that a reasonable certainty of no harm would occur from a child
exposed to TBTO-treated fabric using the revised methodology.  This
revised TBT assessment would have provided a range of risks from these
two studies if the LOD of 100 ppb could be converted to ug/cm2. 
Nonetheless, the second study can not be confirmed as being designed to
represent a reasonable certainty of no harm.  Note:  The application
rates in these studies (i.e., 2.58% and 1.72% by weight product
containing 1% TBTO) are less then the maximum labeled rate for TBTO
(i.e., 3.5% product by weight containing 1.6% TBTO).

The protection factor reducing exposure to TBT residues in the mattress
from the use of a sheet or clothing is 50% based on PHED protection
factor for a single layer of clothing (US EPA 1998).

The child skin area contacting the mattress was assumed to 3,283 cm2
(50% of the total surface area of a toddler) (NAFTA guidance per US EPA
1997).

The adult skin area contacting the mattress was assumed to 9,220 cm2
(50% of the total surface area of an adult) (NAFTA guidance on surface
areas per US EPA 1997).

The chemical specific dermal absorption study is 15%.

The body weight of a child was assumed to be 15 kg.

The body weight of an adult was assumed to be 70 kg

Results

	Table 4.5 shows the calculation of the short and intermediate-term
dermal exposures and MOEs for children and adults contacting treated
mattress covers.  The dermal MOEs are below the target MOE of 1000, and
therefore are of concern for adults and children contacting the cover
and assuming 100% and 5% transfer to skin and the results of one of the
two TBTO leaching studies.  Note:  A second study indicated that the
residue transfer was less then 10 ppb; however there is insufficient
information in the study to convert the 10 ppb to ug/cm2 and it is not
possible to determine if the second study is representative of a high
end exposure potential.  Therefore, the risks are of concern.   

Table 4.5.  Short- and Intermediate-term Dermal Exposures and MOEs for
Children and Adults Contacting Treated Mattress Covers

Duration	% a.i.	Mattress density (mg/cm2)	Fraction transferred to skin
Skin surface area contacting mattress (cm2/day)	Protective factor

(%)	Dermal Absorption

(%)	ST and IT Exposure a 

(mg/kg/day)	Dermal MOE 

(Target MOE = 1000) b

Children

ST/IT	0.056%	10	100%	3,283	50%	15%	0.092	<1



	5%	3,283	50%	15%	0.0046	7

Adults

ST/IT	0.056%	10	100%	9,220	50%	15%	0.055	<1



	5%	9,220	50%	15%	0.0028	11

Study #1 Application Rate:  2.58% product by weight (product containing
1% TBTO)

ST/IT Children	0.026%	NA	0.015 ug/cm2	3,283	50%	15%	0.0037	8

Study #2 Application Rate:  1.72% product by weight (product containing
1% TBTO)

ST/IT Children	0.017%	NA	<10 ppb	3,283	50%	15%	Need more information to
convert LOD of 10 ppb to ug/cm2

a 	Equations used to estimate exposure are presented above for estimates
based on percent transferred.  For study numbers 1 and 2 the absorbed
daily dose (mg/kg/day) = Surface area exposed (cm2) x measured residue
(ug/cm2) x 15% dermal abs x 50% protection factor from sheets x unit
conversion ug to mg (1/1000) x (1/15 kg child BW). 

B	Dermal MOE = BMD10/dermal dose [Where: ST and IT dermal BMD10 = 0.03
mg/kg/day;  Target MOE = 1000]. 

	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
Pesticide Handler Exposure Database (USEPA, 1998) (See Appendix B for
summaries of the data source). Some of the PHED 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. 

Two residue transfer studies were submitted for TBTO.  Both studies
reported results for the mattress ticking.  The data are also used in
this review for estimating risks to the clothing.  The first of two
studies was designed to simulate the “worst-case” of residue
transfer as a screening-level assessment.  The methodology for the
“worst-case” scenario was then refined to attempt to develop a
“reasonable worst-case”.  However, neither method provided
information linking residue transfer to actual human exposure.  The
first study appears to be representative of the high end residue
transfer to be used as a screening-level assessment.  But there is
insufficient information available in the second study to assume that a
reasonable certainty of no harm would occur from a child exposed to
TBTO-treated fabric using the revised methodology.  This revised TBT
assessment would have provided a range of risks from these two studies
if the LOD of 100 ppb could be converted to ug/cm2.  Nonetheless, the
second study can not be confirmed as being designed to represent a
reasonable certainty of no harm.  Note:  The application rates in these
studies (i.e., 2.58% and 1.72% by weight product containing 1% TBTO) are
less then the maximum labeled rates for TBTO.

RESIDENTIAL AGGREGATE RISK ASSESSMENT AND CHARACTERIZATION 

	The inhalation, dermal, and oral endpoints are based on the same
toxicological study/effects, and therefore, it would be appropriate to
estimate aggregate MOEs. The residential uses that could potentially be
aggregated are the paint applications, the textiles, and the mattresses.
 There is the likelihood of co-occurrence for two of the uses but it
would be unlikely that all three uses would co-occur because of the
limited frequency a resident paints coupled with not all paints and/or
textiles are treated with TBT.  Therefore, residential uses could be
aggregated for two of the uses.  However, at this time the risks are of
concern for each of the individual uses, and therefore, there is no need
to aggregate the risks. 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 TBT can occur in six Use
Categories:   agricultural premises and equipment;
commercial/institutional/industrial premises and equipment; material
preservatives; and industrial processes and water systems; antifouling
coatings; and wood preservatives.

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

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

Agricultural Premises and Equipment (Use Category I)

Agricultural/farm/

poultry structures/buildings and equipment	Brush, mop, wipe, spray, and
fogger for poultry farm buildings and poultry hatcheries (incubators,
hatchers, hatchery rooms)	ST/IT Handler:

Inhalation

Dermal	65020-12	Liquid:  0.00033 lb ai/gal

[(0.5 oz formulated product x 1 % ai x 8.34 lb/128 oz) / (1 gal water) =
0.00033 lb ai/gal]

Fogger:  1.3E-6 lb ai/ft3

[(1 gal formulated product x 8.34 lb/gal density x 1 % ai) / (6000ft2 x
10 ft ceiling) = 1.3E-6 lb ai/ft3 as the maximum rate representing
poultry farm buildings]

Commercial/Industrial/Institutional Premises (Use Category III)

(See wood preservative category for commercial painters using treated
stain)	NA	NA	NA	NA

Material Preservatives (Use Category VII)

Caulks, sealants, adhesives, etc	Liquid pour

Metered pump	ST/IT Handler: Inhalation

dermal

	5383-47

(67360-3, 1529-30, and 1529-35)	0.145% ai 

[0.5% formulated product x 29% ai = 0.145% ai or 1450 ppm ai]

MWF 	Liquid pour

Machinist	ST/IT/LT handler/machinist:

Dermal

Inhalation	5383-47	0.145% ai in cutting oil

[0.5% formulated product x 29% ai = 0.145% ai or 1450 ppm ai]

  SEQ CHAPTER \h \r 1 Industrial processes and Water Systems (Use
Category VIII)

Pulp and Paper 

 	Metered pump

	ST/IT Handler: Inhalation

dermal

	47371-29

	Initial:  0.014 lb ai/ton

Continuous:  0.007 lb ai/ton

[Initial:  9.6 oz/ton paper

Continuous feed: 4.8 oz/ton paper.  

Where 9.6 oz  product x 2.25% ai  x 8.34 lb/128 oz = 0.014 lb ai/ton
paper]

Recirculating Cooling Water	Liquid pour

Metered pump	ST/IT Handler: Inhalation

dermal	5185-399	Initial:  0.089 lb ai/1000 gal

Continuous:  0.022 lb ai/1000 gallons of water

[Initial:  40 oz  product x 8.34 lb/128 oz x 3.4% ai /1000 gallons water

Continuous feed: 10 oz  product x 8.34 lb/128 oz x 3.4% ai /1000 gallons
water]

Oil fields and petrochemical water injection systems	Liquid pour

Metered pump	ST/IT Handler: Inhalation

dermal	5185-399	Initial:  0.089 lb ai/1000 gal

Continuous:  0.022 lb ai/1000 gallons of water

[Initial:  40 oz  product x 8.34 lb/128 oz x 3.4% ai /1000 gallons water

Continuous feed: 10 oz  product x 8.34 lb/128 oz x 3.4% ai /1000 gallons
water]

Antifouling Coatings (Use Category IX)

Sonar Domes & Hulls	Unknown	ST/IT Handler:

Inhalation

Dermal

(assumed)	1225-11

74489-01	5.78 % ai in formulation

53% ai in formulation

Wood Preservatives (Use Category X)

Staining 

(commercial painters)	Paint brush,

Airless sprayer	ST/IT Handler:

Inhalation

Dermal	1022-511

(577-539, 577-544, 1022-511, 7313-6, 8177-71)	0.062 lb ai/gallon

[8.3 lbs per gal density x 0.75% ai   = 0.062 lb ai/gallon of stain]

 

	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 mopping scenario, the CMA dermal and inhalation unit exposure
values for ungloved mopping were used (71.6 mg/lb a.i. and 2.38 mg/lb
a.i., respectively).  These values are based on data collected from six
replicates in which the applicator mopped the floor and received
exposure via contact with the mop or with the bucket.  

For the wiping scenario, the CMA dermal and inhalation unit exposure
values for ungloved wiping were used (2,870 mg/lb a.i. and 67.3 mg/lb
a.i., respectively).  These values are based on data collected from six
replicates (dental technicians) who used a finger pump sprayer to apply
the product and then wiped the surfaces with a paper towel

For the low pressure handwand scenarios, the CMA dermal and inhalation
unit exposure values for ungloved use of a low pressure spray were used
(191 mg/lb a.i. and 0.681 mg/lb a.i., respectively).  These values are
based on data collected from eight replicates in which the applicator
hand sprayed carpet using 200 psi, then used a push broom rake to raise
the carpet nap.

For the high-pressure spray scenario, the PHED dermal and inhalation
unit exposure values for liquid/open pour/high pressure spray (PHED
scenario 35) were used (single layer of clothing and gloves). The dermal
and inhalation unit exposure values are 2.5 mg/lb a.i. and 0.12 mg/lb
a.i., respectively.

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. 

Sealants, caulks, grout, etc: 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. 

Fogging:  It is assumed that most of the exposure to the handler will be
due to preparing the fogger, and that the handler leaves the room
immediately after fogging commences.  Therefore, the available CMA
disinfectant liquid pour dermal and inhalation unit exposure values were
used.  The dermal and inhalation unit exposure values are 36.5 mg/lb
a.i. and 1.89 mg/lb a.i., respectively. This value is based on data
collected from two gloved replicates involving pouring a disinfectant
product from a jug into sterilization trays designed for dental
instruments, adding water and instruments to the tray, removing the
instruments, and discarding the old solution.

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 TBT, 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 low-pressure handwand scenario, it was assumed that 10 gallons
of solution are used in agricultural uses.	

For the high-pressure spray scenario, it was assumed that 40 gallons of
solution are used. 

For the mopping scenario, it was assumed that two gallons of solution
are used.

For the wiping scenario, it was assumed that 0.26 gallons were used
based on standard assumptions of the amount used for hard surface
disinfection.

For the fogging scenario in the agricultural use site category, it was
assumed that a poultry house of 600 ft x 66 ft x 10 ft or 39,600 ft 2
area or 396,000 ft3 volume is treated.  

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 to be treated:

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

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

Oil fields:  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 stain 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 stain 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.  In summary, for the non fogging agricultural uses the inhalation
MOEs are greater than 100, and therefore not of concern.  Some of the
dermal MOEs for the same scenarios are above and some below the target
MOE of 100.  However, the use of chemical resistant gloves was not
assessed for all scenarios because the data were not available.  Based
on the low application rate (i.e., 0.00033 lb ai/gallon), the magnitude
of the MOEs, and assuming that chemical resistant gloves would afford
substantial reduction in exposure, these dermal MOEs do not appear to be
of concern if gloves are required on the labels (confirmatory data would
be required).  The MOEs for the material preservative use are below the
target MOE of 100.  Potential mitigation for material preservative
additives would be to require closed loading systems.  The industrial
process and water system uses also need to be restricted to closed
loading systems.  At this time, it is unclear how the antifouling
coatings are applied and additional information on the application
techniques are requested.  Finally, the commercial application of stains
indicate MOEs of concern (i.e., MOEs less than 1).

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 Agricultural Premises and Equipment (Use Site
Category I )

Agricultural/farm/

poultry structures/buildings and equipment	Brush-on	0.28	180 no gloves

(24 gloves)	0.00033

lb ai/gal	5 gal	6.6E-6	0.00064	4500	47 (350 gloves)

	Wipe	67.3	2870

0.26 gal	8.2E-5	0.00053	360	57

	Mop	2.38	71.6

2 gal	2.2E-5	0.001	1300	300

	Spray 

(hand held)	0.681	191

10 gal	3.2E-5	0.0014	930	22

	Spray

(mechanical)	0.12	2.5

40 gal	2.3E-5	7.1E-5	1300	420

	Fogger	1.89	36.5	1.3E-6 

lb ai/ft3	396,000 ft3	0.014	0.040	2	<1



Commercial, Institutional and Industrial Premises and Equipment (Use
Site Category III )

(See wood preservative category for commercial painters using treated
stain)

Material Preservatives (Use Site Category VII)

Caulks, adhesives, grout, etc. (manufacturing process)	Liquid pour
0.00346	0.135 (gloves)	0.145% ai	2000 lbs	0.00014	0.00084	210	36

	Liquid pump	0.000403	0.454

10,000 lbs	8.3E-5	0.014	360	2

MWF	Liquid pour	0.00854	0.184	0.145% ai	300 gal (2,500 lbs)	0.00044
0.0014	68	21

Industrial Processes and Water Systems (Use Site Category VIII)

Pulp and Paper	Metering pump	0.000265	0.00454

(gloves)	0.014 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)	0.089 lb ai/1000 gal	5E7 gallons









	Oil fields and petrochemical water injection systems	Pour liquid	0.45
10.1

(gloves)	0.089 lb ai/1000 gallons treated (3.4% ai)	5 gal product

(41.7 lbs)	0.0091	0.031	3	3

	Metering pump	0.000265	0.00454

(gloves)

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

Antifouling Paints (Use Site Category IX)

Sonar Domes & Hulls	Specialty use.  Application rates and methods are
unknown.

Wood Preservatives (Use Site Category X)  

Painting/staining (commercial)	Paint brush	0.28	180	0.062 

lb ai/gal	5 gallons	0.0012	0.12	24	<1

	Airless sprayer	0.83	38

50 gallons	0.037	0.25	<1	<1

	

a	Absorbed Daily dose (mg/kg/day) = [unit exposure (mg/lb a.i.) x
absorption factor (dermal 0.15) x application rate x quantity treated /
Body weight (70 kg).

	b	MOE = NOAEL  (mg/kg/day) / Daily Dose [Where ST and IT inhalation
BMD10 = 0.03 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 TBT-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 TBT 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 plus the forearms (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 and forearms is 2013 cm2 (USEPA 1997)

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

The percent active ingredient in treated metalworking fluid is 1450 ppm
(i.e., 0.145% ai) calculated from 0.5% formulated product x 29% ai (EPA
Registration No. 5383-47).

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 1450 ppm
(i.e., 0.145% ai) calculated from 0.5% formulated product x 29% ai (EPA
Registration No. 5383-47).

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 below the target MOE of 100 for all durations.   

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 & Forearm Surface Area (cm2)	Film thickness (mg/cm2)	

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

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

Dermal a

(mg/kg/day)	

Inhalation. b 

(mg/kg/day)	

Dermal MOE 

(Target MOE = 100)c	Inhalation MOE 

(Target MOE = 100)d

0.145	2013	1.75	1	5	1.0	8	0.011	0.00083	3	36



a	Dermal Daily Dose (mg/kg/day) = [(% active ingredient * hand & forearm
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 = BMD10 (mg/kg/day) / Daily Dose (mg/kg/day) [Where:
ST/IT/LT dermal BMD10  = 0.03 mg/kg/day; target MOE = 100]. 

d	Inhalation MOE = BMD10 (mg/kg/day) / Daily Dose (mg/kg/day) [Where:
inhalation BMD10 = 0.03 mg/kg/day for all durations; target MOE = 100
for all durations]

Fogging (Poultry farm building)

	Post-application inhalation exposure (to aerosols) was assessed for
entry into a poultry farm building after a fogging application.  The
inhalation exposures and resulting REIs are based on modeling of the
aerosols from the maximum application rate.  Fogging poultry farm
buildings based on the label rate is assumed to be the high end of the
air concentrations (mg/m3) when fogging the incubators, hatchers, and
hatchery rooms.  The air concentration applied and the air exchange
rates of the structure are used to estimate the REIs.  Therefore,
nuances in the treatment of poultry farm buildings versus poultry
hatcheries are based on the target air concentration application rate. 
Any dermal post application is presumed to be negligible.  The
inhalation exposure assessment was conducted using the Multi-Chamber
Concentration and Exposure Model (MCCEM v1.2).   MCCEM estimates average
and peak indoor air concentrations of chemicals released from products
or materials in houses, apartments, townhouses, or other residences. 
Although the data libraries contained in MCCEM are limited to
residential settings, the model can be used to assess other indoor
environments.  

	The MCCEM model was executed utilizing the rate of 1.3E-6 lb ai/ft3
(EPA Reg No. 65020-12 states to fog 1 gallon of product per 6,000ft2 of
floor space and EPA assumed 10 ft ceilings to calculate an air
concentration per volume) for poultry houses. Upon commencement of
fogging activities, TBT labels state that the building should be well
ventilated and not entered until 1 to 4 hours after fogging.  If the
building must be entered, the label states individuals entering the
building must wear a self-contained respirator approved by NIOSH/MSHA,
goggles, long sleeves and long pants.  Therefore, exposure was
calculated for a person entering the building 1, 2, and 4 hours after
all the applied fogger has been deployed.  The following assumptions
were included along with the standard input parameters of the MCCEM
model.

The area being fogged is a one-chamber barn with dimensions of 600ft x
66ft x 10ft (AD standard assumption).

For the poultry structures, the air exchange rate is 4 per hour based on
the rate for a poultry barn (Jacobson, 2005).

Fogging occurs instantaneously, so that the entire mass of product is
mixed homogeneously with the indoor air as soon as fogging commences.  

It is assumed that all of the aerosols are inhalable and/or respirable.

	A detailed report is presented in Appendix B, including air
concentrations reported for every 10 minutes for several days.  Upon
entry after 1 hour, the 8-hour time weighted average (TWA) air
concentration for a worker exposed for 8 hours the MOEs is less then the
target MOE of 100 (i.e., MOE = 17).  However, the MOE is greater than
the target MOE of 100 if the REI is set at 2 hours and there are 4 air
exchange rates per hour (ACH).  If specific REIs are warranted for
hatcheries that differ from 2 hours, a comparison of the fogging
concentration rates (e.g., mg/m3) should be discussed during mitigation.

Table 22.  Short and Intermediate Term Inhalation Risks Associated with
Postapplication Exposure to TBT After Fogging a Poultry House

Parametera	Value	Rationale

Dimensions	600 ft x 66t x10 ft,

39,600 ft2 floor area,

396,000 ft3 (11214 m3)

volume	Standard AD assumption

Air Changes per Hour (ACH)*	4/hr	Jacobson, 2005

Activity Pattern*	Time Weighted Average (TWA) starting at expiration of
1 and 4 hr REI	Based on product’s re-entry interval

Concentration of Fogging Liquid	Not needed lb ai/gal	Product Label
(65020-12)

Use rate	1.3E-6 lb ai/ft3	Product label states to fog 1 gal product/6000
ft2 x 10 ft ceiling (ceiling height assumed)  

Concentration in room after fogging (initial concentration rate at time
0)*	20.61 mg ai/m3	See Appendix B spreadsheet

Body Weight	70 kg (adult)	NAFTA  (USEPA, 1997)

Inhalation Rate	1.0 m3/hr	NAFTA Light Activity for Adults (USEPA, 1997)

MCCEM OUTPUT	1 hour REI	2 hour

REI	4 hour REI

	Concentration after appropriate REI (mg/m3)	0.377	0.0069	2.3E-6	MCCEM
calculated air concentration

8-hour Time Weighted Average (TWA) air concentration  (mg/m3)	0.016

(TWA from 1 to 9 HAT)	2.9E-4

(TWA from 1 to 9 HAT)	9.7E-8

(TWA from 4 to 12 HAT)	MCCEM-calculated 8-hr TWA air concentration
starting after REI for 8 hour working shift 

Dose (mg/kg/day)	0.0018	3.3E-5	1.1E-8	(TWA Air Conc.) x (Exposure Time
of 8 hr) x (Inhal. Rate) / BW (70kg)

Short-term MOE	17	910	2.7E+6	BMD10 (0.03 mg/kg/day) / Dose

*Used as MCCEM input.  Default values from MCCEM were used for all
inputs not listed in the table above.

HAT = hours after treatment.

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 

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.

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.



Appendix B

MCCEM Output

Air Concentration Estimates for Fogging Poultry Houses



Time (days)	Time (hour)	Conc Outdoors (mg/m³)	Conc Zone 1 (mg/m³)
Conc@Person(mg/m³)

0	0	0	20.61	0

0.00694444	0.1666666	1.12E-55	10.5816	10.5816

0.0138889	0.3333336	1.70E-55	5.43277	5.43277

0.0208333	0.4999992	2.00E-55	2.78928	2.78928

0.0277778	0.6666672	2.15E-55	1.43207	1.43207

0.0347222	0.8333328	2.23E-55	0.735252	0.735252

0.0416666	0.9999984	2.27E-55	0.377492	0.377492

0.0486111	1.1666664	2.29E-55	0.193811	0.193811

0.0555555	1.333332	2.30E-55	0.0995064	0.0995064

0.0625	1.5	2.31E-55	0.0510884	0.0510884

0.0694444	1.6666656	2.31E-55	0.0262297	0.0262297

0.0763888	1.8333312	2.31E-55	0.0134668	0.0134668

0.0833333	1.9999992	2.31E-55	0.00691413	0.00691413

0.0902777	2.1666648	2.31E-55	0.00354984	0.00354984

0.0972222	2.3333328	2.31E-55	0.00182255	0.00182255

0.104167	2.500008	2.31E-55	0.000935733	0.000935733

0.111111	2.666664	2.31E-55	0.000480423	0.000480423

0.118055	2.83332	2.31E-55	0.000246658	0.000246658

0.125	3	2.31E-55	0.000126639	0.000126639

0.131944	3.166656	2.31E-55	6.50E-05	6.50E-05

0.138889	3.333336	2.31E-55	3.34E-05	3.34E-05

0.145833	3.499992	2.31E-55	1.71E-05	1.71E-05

0.152778	3.666672	2.31E-55	8.80E-06	8.80E-06

0.159722	3.833328	2.31E-55	4.52E-06	4.52E-06

0.166667	4.000008	2.31E-55	2.32E-06	2.32E-06

0.173611	4.166664	2.31E-55	1.19E-06	1.19E-06

0.180555	4.33332	2.31E-55	6.11E-07	6.11E-07

0.1875	4.5	2.31E-55	3.14E-07	3.14E-07

0.194444	4.666656	2.31E-55	1.61E-07	1.61E-07

0.201389	4.833336	2.31E-55	8.27E-08	8.27E-08

0.208333	4.999992	2.31E-55	4.25E-08	4.25E-08

0.215278	5.166672	2.31E-55	2.18E-08	2.18E-08

0.222222	5.333328	2.31E-55	1.12E-08	1.12E-08

0.229167	5.500008	2.31E-55	5.75E-09	5.75E-09

0.236111	5.666664	2.31E-55	2.95E-09	2.95E-09

0.243055	5.83332	2.31E-55	1.52E-09	1.52E-09

0.25	6	2.31E-55	7.78E-10	7.78E-10

0.256944	6.166656	2.31E-55	4.00E-10	4.00E-10

0.263889	6.333336	2.31E-55	2.05E-10	2.05E-10

0.270833	6.499992	2.31E-55	1.05E-10	1.05E-10

0.277778	6.666672	2.31E-55	5.41E-11	5.41E-11

0.284722	6.833328	2.31E-55	2.78E-11	2.78E-11

0.291666	6.999984	2.31E-55	1.43E-11	1.43E-11

0.298611	7.166664	2.31E-55	7.32E-12	7.32E-12

0.305555	7.33332	2.31E-55	3.76E-12	3.76E-12

0.3125	7.5	2.31E-55	1.93E-12	1.93E-12

0.319444	7.666656	2.31E-55	9.90E-13	9.90E-13

0.326389	7.833336	2.31E-55	5.08E-13	5.08E-13

0.333333	7.999992	2.31E-55	2.61E-13	2.61E-13

0.340278	8.166672	2.31E-55	1.34E-13	1.34E-13

0.347222	8.333328	2.31E-55	6.88E-14	6.88E-14

0.354166	8.499984	2.31E-55	3.53E-14	3.53E-14

0.361111	8.666664	2.31E-55	1.81E-14	1.81E-14

0.368055	8.83332	2.31E-55	9.31E-15	9.31E-15

0.375	9	2.31E-55	4.78E-15	4.78E-15

0.381944	9.166656	2.31E-55	2.45E-15	2.45E-15

0.388889	9.333336	2.31E-55	1.26E-15	1.26E-15

0.395833	9.499992	2.31E-55	6.47E-16	6.47E-16

0.402778	9.666672	2.31E-55	3.32E-16	3.32E-16

0.409722	9.833328	2.31E-55	1.71E-16	1.71E-16

0.416666	9.999984	2.31E-55	8.76E-17	8.76E-17

0.423611	10.166664	2.31E-55	4.50E-17	4.50E-17

0.430555	10.33332	2.31E-55	2.31E-17	2.31E-17

0.4375	10.5	2.31E-55	1.19E-17	1.19E-17

0.444444	10.666656	2.31E-55	6.09E-18	6.09E-18

0.451389	10.833336	2.31E-55	3.12E-18	3.12E-18

0.458333	10.999992	2.31E-55	1.60E-18	1.60E-18

0.465277	11.166648	2.31E-55	8.24E-19	8.24E-19

0.472222	11.333328	2.31E-55	4.23E-19	4.23E-19

0.479166	11.499984	2.31E-55	2.17E-19	2.17E-19

0.486111	11.666664	2.31E-55	1.11E-19	1.11E-19

0.493055	11.83332	2.31E-55	5.72E-20	5.72E-20

0.5	12	2.31E-55	2.94E-20	2.94E-20



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