EPA600/R-07/040F | September 2007 | www.epa.gov/ncea
United States
Environmental Protection
Agency
               Dermal Exposure Assessment:
               A Summary of EPA Approaches
National Center for Environmental Assessment
Office of Research and Development, Washington, DC 20460

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                                    EPA/600/R-07/040F
                                    September 2007
 Dermal Exposure Assessment:
A Summary of EPA Approaches
  National Center for Environmental Assessment
     Office of Research and Development
    U.S. Environmental Protection Agency
          Washington, DC 20460

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                                       DISCLAIMER


       This document has been reviewed in accordance with U.S. Environmental Protection
Agency policy and approved for publication. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
Preferred Citation:
U.S. Environmental Protection Agency (EPA). (2007) Dermal exposure assessment: A summary of EPA
approaches. National Center for Environmental Assessment, Washington, DC; EPA/600/R-07/040F. Available
from the National Technical Information Service, Springfield, VA, and online at http://www.epa.gov/ncea.
                                              11

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                               CONTENTS

LIST OF TABLES	iv
LIST OF ABBREVIATIONS AND ACRONYMS	v
PREFACE	ix
AUTHORS, CONTRIBUTORS, AND REVIEWERS	xii

1.     INTRODUCTION	1
      1.1.   PURPOSE	1
      1.2.   DERMAL EXPOSURE CONSIDERATIONS	2
      1.3.   DERMAL ABSORPTION CONSIDERATIONS	3
           1.3.1.  In Vivo Dermal Absorption Methods	4
           1.3.2.  In Vitro Dermal Absorption Methods	5
           1.3.3.  In Vivo/In Vitro Dermal Absorption Method Comparisons	6

2.     U.S. EPA APPROACHES TO DERMAL EXPOSURE ASSESSMENT	7
      2.1.   OFFICE OF PREVENTION, PESTICIDES, AND TOXIC SUBSTANCES
           (OPPTS)	7
           2.1.1.  Office of Pollution Prevent!on and Toxics (OPPT)	7
           2.1.2.  Office of Pesticide Programs (OPP)	10
      2.2.   OFFICE OF SOLID WASTE AND EMERGENCY RESPONSE (OSWER)	18
      2.3.   OFFICE OF WATER (OW)	21
      2.4.   OFFICE OF RESEARCH AND DEVELOPMENT (ORD)	22

3.     DERMAL EXPOSURE ASSESSMENT COMPARISONS	24
      3.1.   TARGET POPULATIONS, EXPOSURE MEDIA AND EXPOSURE
           PARAMETERS FOR DERMAL EXPOSURE ASSESSMENTS	24
           3.1.1.  Target Populations	24
           3.1.2.  Exposure Media	31
           3.1.3.  Assumed and Default Parameters for Exposure Assessment	33
      3.2.   METHODOLOGY COMPARISON	33
           3.2.1.  Skin Loading Adherence Factors	33
           3.2.2.  Selection of a Permeability Coefficient	34
           3.2.3.  Selection of a Transfer Coefficient	35
      3.3.   DERMAL EXPOSURE ASSESSMENT METHODOLOGY FOR
           VARIOUS MEDIA	35

4.     DERMAL EXPOSURE ASSESSMENT TRENDS AND RESEARCH NEEDS	37
      4.1.   WATER	37
      4.2.   SOIL	38
      4.3.   TREATED SURFACES	38

5.     CONCLUSIONS	40

REFERENCES	42
                                   in

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                                 LIST OF TABLES

1.     Target populations and assumed characteristics for dermal exposure assessment	25

2.     Exposure media considered for dermal exposure assessment	27

3.     Assumed and default exposure parameters for target populations for dermal
      exposure assessment	28

4.     Dermal exposure assessment methodology for chemical contaminants in air	32

5.     Dermal exposure assessment methodology for chemical contaminants in water	32

6.     Dermal exposure assessment methodology for chemical contaminates in soil	35

7.     Dermal exposure assessment methodology for treated surfaces	36

8.     Dermal exposure assessment methodology for occupational sources	36
                                         IV

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General
                   LIST OF ABBREVIATIONS AND ACRONYMS
ai
CHAD
ChemSTEER
DEA
EAG
EFAST
EFH
EPA
ERDEM
HEDS
MCL
MCLG
NCEA
NERL
NHEERL
OPP
OPPT
OPPTS
ORD
OSRTI
OSWER
OW
PBPK
PCB
PHED
PIRAT
PPS
QSAR
RAF
RAGS
RAGSE
SHEDS
SOP
WTC
active ingredient
Consolidated Human Activity Database
Chemical Screening Tool for Exposures and Environmental Releases
Dermal Exposure Assessment
Exposure Assessment Group
Exposure, Fate Assessment Screening Tool
Exposure Factors Handbook
Environmental Protection Agency
Exposure Reconstruction and Dose Estimation Model
Human Exposure Database System
Maximum contaminant level
Maximum contaminant level goal
National Center for Environmental Assessment
National Exposure Research Laboratory
National Health and Environmental Effects Research Laboratory
Office of Pesticide Programs
Office of Pollution Prevention and Toxics
Office of Pollution Prevention and Toxic Substances
Office of Research and Development
Office of Superfund Remediation and Technology Innovation
Office of Solid Waste and Emergency Response
Office of Water
Physiologically based pharmacokinetic
Polychlorinated biphenyls
Pesticide Handlers Exposure Database
Pesticide Inert Risk Assessment Tool
Percutaneous Penetration Subgroup
Quantitative structure-activity relationship
Risk Assessment Forum
Risk Assessment Guidance for Superfund
Risk Assessment Guidance for Superfund, Part E
Stochastic Human Exposure and Dose Simulation
Standard Operating Procedure
World Trade Center

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              LIST OF ABBREVIATIONS AND ACRONYMS (continued)
OPPTS: ChemSTEER
ADD
APDR
AT
Ate
BW
Dexp
ED
EY
FT
LADD
Qu
             Average [potential] daily dose
             Acute potential dose rate
             Work-life averaging time
             Lifetime averaging time for chronic exposure
             Body weight
             Dermal potential dose rate
             Days exposed per year
             Years of occupational exposure
             Event frequency
             Lifetime average [potential] daily dose
             Quantity remaining on skin
             [surface loading per event]
             Skin surface area
             Weight fraction of chemical in liquid
(mg/kg-d)
(mg/kg-d)
(yr)
(yr)
(kg)
(mg/d)
(d/site-yr)
(yr)
(events/site-d)
(mg/kg-d)
(mg/cm2-event)
                                                           (cm2)
OPPTS: EFAST
ADD        Average daily potential dose
ADR        Acute potential dose rate
AT          Averaging time

CEM        Consumer exposure model
Dose        Daily potential dose
FQ          Frequency
LADD       Lifetime average daily potential dose
Kp           Skin permeability coefficient
Kow          Octanol/water partition coefficient
MW         Molecular weight
SA/BW      Surface area/body weight
Q            Amount retained on the skin
             [surface loading per event]
WF          Weight fraction  of product
Y            Years of use
                                                           (mg/kg-d)
                                                           (mg/kg-d)
                                                           (yr for ADD and LADD,
                                                           d for ADR)

                                                           (mg/kg-d)
                                                           (events/yr)
                                                           (mg/kg-d)
                                                           (cm/h)

                                                           (g/mol)
                                                           (cm2/kg)
                                                           (g/cm2-event)
                                                           (yr)
                                          VI

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OPP
              LIST OF ABBREVIATIONS AND ACRONYMS (continued)
A           Maximum area treated
ADR        Absorbed Dose Rate
AR          Maximum application rate

AT          Averaging time (yr)
CF, CF#     Conversion factors, e.g., "CF1 = (0.001 mg/ug)"
Cw          Concentration of ai in the water
D           Fraction of residue that dissipates daily , OR
D           [Potential] Dose
DFRt        Dislodgeable residue on day t
ED          Exposure duration
EF          Exposure frequency
ET          Exposure time
F            Fraction of ai retained on surface
FR          Flux rate for the product of concern
ISRt         Indoor surface residue on day t
LADD       Lifetime average [potential] daily dose
fi            Specific gravity of paint
N           Number of cans applied
P            Percent by weight of ai  in paint
PDR         Potential dose rate
PDRt        Potential dose rate on day t
SA          [Skin] surface area
t            Post-application day when exposure is assessed
T            Fraction of residue transferred to skin
Tc          Transfer coefficient
UE          Unit exposure
V           Maximum volume treated
                                              (acre/d or gal/d)

                                              (Ib ai/acre, Ib ai/ft2,
                                              or Ib ai/gal)
                                              (mg/L)

                                              (mg/kg-d)
                                              (ug/cm2)
                                              (yr)
                                              (d/yr)
                                              (h/d)

                                              (mg/m2/d)
                                              (ug/cm2)
                                              (mg/kg-d)
                                              (g/mL)
                                              (cans/d)

                                              (mg/d)
                                              (mg/d)
                                              (cm2)
                                              (cm2/h)
                                              (mg/lb ai)
                                              (gal/d)
OPPT: PIRAT
A
ABS
AR
area treated or amount used
absorption value
application rate
(ft2/d; gal/d)
(lb/ft2; gal/d; Ib/gal; mg/d)
                                          vn

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              LIST OF ABBREVIATIONS AND ACRONYMS (continued)
BW
PDR
UE
WF
             body weight
             potential dose rate [dose]
             PHED Dermal Unit Exposure
             weight fraction
(kg)
(mg/kg/d)
(mg/lb)
OSWER: Superfund
ABSd
AF
AT
BW
CF
Csoii
Cw
DAD
ED
EF
EV
FA

Kow
Kp
RME
SA
tevent-RME
             Dermal-soil absorption value
             Soil adherence factor
             Averaging time
             Body weight
             Conversion factor
             Concentration in soil
             Concentration in water
             Absorbed dose per event
             Dermal absorbed dose
             Exposure duration
             Exposure frequency
             Event frequency
             Net fraction available in stratum corneum
             for absorption after exposure has ended
             Octanol-water partition coefficient
             Permeation [permeability?] coefficient
             Reasonable maximum exposure
             [Skin] Surface area
             Event duration
(mg/cm )
(yr or d)
(kg)
(mg/cm -event)
(mg/kg-d)
(yr)
(d/yr)
(events/d)
(cm/h)
(mg/kg-d)
(cm2)
(hr)
                                         Vlll

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                                      PREFACE

       Dermal exposure can be an important pathway in environmental health risk assessments.
Exposure can occur from working or playing in contaminated water, soil, or sediment or from
contact with treated or contaminated surfaces indoors or outdoors. Not surprisingly there are
numerous activities and events where dermal exposure can occur and a number of methods and
models have been developed to estimate this route of exposure.
       Agency programs evaluate intentional and incidental dermal exposure for the general
public  and in some cases for workers based on various regulatory mandates and activities. The
Office  of Pesticide Programs (OPP) considers dermal exposure for pesticide application to
pesticide workers and to consumers. The Office of Pollution Prevention and Toxics (OPPT)
considers dermal exposure for consumer products containing high volume use chemicals and to
chemical production workers for production of new chemicals.  The Office of Water (OW)
assesses dermal exposure to organic compounds during bathing, and the Office of Solid Waste
and Emergency Response (OSWER) deals with dermal  exposure to workers for hazardous waste
site cleanup and to residents for incidental contact with  chemically contaminated water, soil, and
sediment from these sites.
       The National Center for Environmental Assessment (NCEA) conducts research to
improve exposure and risk assessment methods, models, and guidance. Dermal exposure
projects are being conducted for identification of the chemical and physical properties of soil that
affect chemical movement from soil to skin, development of mechanistic models for dermal
penetration of contaminants in water and soil, and evaluation of in vitro dermal absorption test
methods, in particular those for analysis of highly lipophilic compounds. This research is
conducted in close cooperation with Agency program office staff to ensue it is designed to meet
Agency needs and is conducted in close collaboration with other researchers throughout the
world to benefit from their viewpoints and expertise.
       This report was produced as a result of an internal dialogue among a group of exposure
assessors from different Agency programs. When OPPT began an update of its Chemical
Screening Tool for Exposures and Environmental Releases and Consumer Exposure Models in
2003, the staff looked outward for comments on their standard operating procedures,  approaches,
and assumptions. They convened meetings with various experts on dermal exposure  assessment
from around the Agency to discuss recent advances and the current state of dermal exposure
assessment practice. These experts recognized there would be a benefit to describe the different
approaches used to conduct dermal exposure assessment in the Agency.  The result would
increase awareness and understanding of alternate approaches to estimate dermal penetration and
identify areas where approaches might be harmonized to exchange information and to share
methods and data to improve the transparency of dermal exposure assessment in the Agency.
                                          IX

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       To achieve this, an ad hoc group of scientists formed to initiate this effort. They
identified other Agency experts and offices where dermal exposure assessment is practiced.
They eventually brought their effort to the attention of the Risk Assessment Forum (RAF) and
suggested the effort be conducted as a RAF project because of its Agency-wide scope and value.
A committee was formed to explore the merits of the issue. Their efforts resulted in the RAF
commissioning a report in 2004 documenting and comparing the approaches, assumptions, and
methods used across the Agency for dermal exposure assessment.  This report was used in turn
to prime the dialogue at a RAF sponsored cross-Agency colloquium, the Colloquium on Dermal
Exposure Methods Comparison in 2005, to identify common factors and differences of dermal
exposure assessment methods, to identify opportunities for harmonization among different
dermal exposure assessment methods, and to determine future research needs (U.S. EPA,  2005).
       Coincidentally, the RAF report and colloquium coincided with NCEA research efforts to
evaluate methods used to estimate permeability coefficients (Kp) and to assess the importance of
dermal exposure to chemically contaminated water, soil, and sediment. Kp is a key ingredient in
dermal exposure equations but estimates are subject to great variability due to different methods
in use to generate them.  Moreover, because many chemicals of interest to the Agency do not
have a Kp reported in the literature, evaluation of dermal absorption methods and models to
obtain Kp represented a major focus of the NCEA dermal research program. Likewise, because
little is known about the mechanics of dermal absorption from contact with chemically
contaminated soil, NCEA initiated studies to ascertain the physical and chemical characteristics
of chemicals bound to soil particles and the influence of soil particles on dermal absorption.
       The Agency's interest in harmonization of dermal exposure assessment methods is to
improve the efficiency and transparency of dermal risk assessment. It is intended to reduce the
burden of repeated testing, information and data collection; foster information exchange across
the Agency; apply current science and provide complete documentation for Agency methods;
and to stimulate research in  areas where it is needed.  Participants discussing harmonization at
the Dermal Exposure Methods Comparison Colloquium in 2005 supported greater interaction
among the different program offices at EPA and encouraged collaboration with external
organizations such as the Agency for Toxic Substances and Disease Registry; the National
Institute for Occupational Safety and Health; the European Union; and the World Health
Organization, to promote data sharing and more effective utilization of existing databases.
       However, as described in this report, harmonization of dermal exposure assessment
procedures is difficult for several reasons. First, regulatory mandates necessitate that Agency
programs focus on specific chemicals of interest in different media. Not surprisingly the
physical and chemical characteristics of pesticide compounds, hazardous wastes, and water
contaminants can be substantially different.  Second, exposure scenarios considered by the
Agency programs are substantially different due to the nature of the exposures that occur in the
environment. For example chemical exposure associated with residential pesticide usage is

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substantially different from contact with chemically contaminated soil migrating from a nearby
hazardous waste site or dermal exposure to organic compounds in contaminated water during
showering. Third, the procedures currently used to estimate surface contact and dermal
absorption require different input variables that are not interchangeable. The net result is
different approaches are being used in the Agency to estimate dermal exposure.
       Despite these difficulties to harmonize dermal exposure assessment procedures, the intent
of this report is to focus on dermal penetration methods and the issues the Agency faces in
assessing dermal exposure. Accordingly this report is anticipated to serve as a useful reference
for Agency exposure assessors to

   (1) describe the current scope of dermal exposure assessment methods in the Agency;
   (2) identify and enable sharing of common approaches, models, methods,  and databases;
   (3) identify areas where harmonization might proceed to foster efficiency  and transparency;
   (4) and identify areas where more research is needed to improve the precision and accuracy
       of dermal exposure assessments.
                                           XI

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                  AUTHORS, CONTRIBUTORS, AND REVIEWERS


       The National Center for Environmental Assessment (NCEA) was responsible for
preparing this report. Major portions were produced by the Battelle Memorial Institute under
Contract Number EP-C-04-027 under the direction of Gary W. Bangs (OSA) who served as the
work assignment manager. Michael Dellarco (NCEA) and Gary W. Bangs authored the final
report with contributions provided by Agency  scientists, risk assessors, and members of the
Agency's Risk Assessment Forum Exposure Assessment Oversight Group. A special thank you
goes to Jennifer Sahmel of ChemRisk (formerly with the Agency's Office of Toxic Substances)
who initially conceived of the idea to compare dermal exposure methods across the Agency.

Contributors:
Denis Borum, U.S. EPA, Office of Water, Washington, DC
Daniel Chang, U.S. EPA, National Exposure Research Laboratory, Las Vegas, NV
Nancy Chiu, U.S. EPA, Office of Water, Washington, DC
Curtis Dary,  U.S. EPA, National Exposure Research Laboratory, Las Vegas, NV
Jennifer Sahmel, ChemRisk, Boulder, CO (formerly of the U.S. EPA, Office of Pesticides and
    Toxic Substances, Washington, DC)

EPA Reviewers:
David Crawford, U.S. EPA, Office of Superfund Remediation and Technology Innovation,
    Washington, DC
Jeff Dawson, U.S. EPA, Office of Pesticide Programs, Washington, DC
John Schaum, U.S. EPA, National Center for Environmental Assessment, Washington, DC
Daniel Stralka, U.S. EPA, Region 9, San Francisco, CA

External Reviwers:
Ronald E. Baynes, North Carolina State University, Raleigh, NC
Leena A.  Nylander-French, The University of North Carolina at Chapel Hill, School of Public
    Health, Chapel Hill, NC
Jagdish Singh, North Dakota State University, Fargo, ND
                                         xn

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                               1.   INTRODUCTION

1.1.   PURPOSE
      This report provides brief summaries of the approaches to dermal exposure assessment to
toxic chemicals used by the various offices of the U.S. Environmental Protection Agency (EPA).
These include the component offices, the Office of Pesticide Programs (OPP) and the Office of
Pollution Prevention and Toxics (OPPT) in the Office of Prevention, Pesticides, and Toxic
Substances (OPPTS); the Office of Superfund Remediation and Technology Innovation (OSRTI)
in the Office of Solid Waste and Emergency Response (OSWER); the Office of Water (OW);
and the Office of Research and Development (ORD).
      The approaches that are summarized here are extracted primarily from documents and
electronically available information that constitute the published guidance and support
documents for dermal exposure assessment from the U.S. EPA offices listed above.  Information
sources include the following among others:

   •  Dermal Exposure Assessment: Principles and Applications, Interim Report (U.S. EPA,
      1992a)
   •  Standard Operating Procedures (SOPs) for Residential Exposure Assessments (U.S. EPA,
      1997'a)
   •  Summary Report for the Workshop on Issues Associated with Dermal Exposure and
      Uptake (U.S. EPA, 2000a)
   •  Risk Assessment Guidance for Superfund (RAGS), Vol I: Human Health Evaluation
      Manual (Part E, Supplemental Guidance for Dermal Risk Assessment [RAGS E]), Final
      (U.S. EPA, 2004a)
   •  Guidelines for Exposure Assessment (U.S. EPA, 1992b)
   •  ChemSTEER - Chemical Screening Tool for Exposures and Environmental Releases
      (U.S. EPA, 2004b)
   •  EFAST - Exposure, Fate Assessment Screening Tool (U.S. EPA, 2007a)
   •  U.S. EPA Exposure Research Abstracts (U.S. EPA, 2004c)
   •  Pesticide Handlers Exposure Database (PHED) surrogate guide
   •  Office of Pesticides Programs 875  Guidance Document
   •  U.S. EPA Exposure Research Models (U.S. EPA, 2004d)
   •  Example Exposure Scenarios (U.S. EPA, 2003a)
   •  Informal discussions with several staff in the relevant EPA offices

      This document does not include recommendations regarding the appropriate approaches
to use nor does it address risk estimation.  Some of the information sources above do address
                                          1

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risk, for example the Superfund guidance (U.S. EPA, 2004a).  Available toxicity and other data
useful in estimating risk based on these exposure assessments can be obtained from the following
references and databases among others: Integrated Risk Information System (U.S. EPA, 2007b),
Registry of Toxic Effects of Chemical Substances (NIOSH, 1997), PHED (2007), Agency for
Toxic Substances and Disease Registry Toxicological Profiles (ATSDR, 2007), Toxicology Data
Network (TOXNET, 2007).

1.2.    DERMAL EXPOSURE CONSIDERATIONS
       Classically exposure is described as the amount of an agent that contacts the outer
boundary of the body.  However, this definition of exposure is limited because the real interest in
risk assessment is the amount of an agent that breeches the outer boundary of the body (dose)
and is capable of being distributed to one or more organs to exert a toxic effect (target dose). For
dermal exposure to occur, an individual must have contact with the chemical in a given medium.
The amount of exposure will depend on the  concentration of the chemical contacting a given
area of skin—the dermal loading or  skin adherence, the ability of the chemical to penetrate and
pass through intact skin—the dermal dose, and the duration and frequency of contact in terms of
the intervals of contact and the number of intervals per day, weeks, months or even  a lifetime.
       Correspondingly, in dermal exposure assessment, the contaminant concentration is the
amount of chemical contaminant in the media, such as water or soil available for contact.  The
potential dermal dose is the amount  of a chemical which could be deposited on the skin during a
given activity. The absorbed  dermal dose is the amount of a chemical that is absorbed into the
body through the skin. The target dose is the amount of absorbed chemical that exerts a toxic
effect at the site of contact or is distributed throughout the body to one or more target organs to
exert a toxic effect. These features are reflected in the various measurement methods and models
used in the Agency to estimate dermal exposure.
       Individuals may be exposed to toxic  chemicals in the workplace through contact with
industrial and commercial chemicals, products or intermediates.  They may also be exposed in
non-occupational settings—their homes, schools, play areas, etc.—as they work or play, through
contact with chemicals emitted into the environment from industrial sources or hazardous waste
sites or contact with chemicals in consumer  products.  Exposure to toxic chemicals can occur
through contact in any environmental medium.  Dermal exposure is most likely to occur through
contact with chemically contaminated surfaces, soil, sediment, liquids, and water. Exposure may
also occur through the air pathway, for example, through aerosols from use of consumer
products. In the workplace, the exposure media may contain industrial products and
intermediates, chemical mixtures, or neat (pure) chemicals.  Outside the workplace, dermal
exposures are most likely to occur through contact with treated surfaces such as turf, chemically
contaminated surfaces, soil, sediment, water, and consumer product usage.

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       The site of dermal exposure is directly related to the activity being performed at the time
of exposure. Depending on the contaminated media and anatomical site of contact, the
contaminants may be absorbed differently. Several factors can influence dermal exposure
(Jackson, 1999; Kissel et al., 1996).  These include:

   •   Reduction or increases in the chemical contact with skin due to clothing;
   •   Protective clothing and gloves and the amount of protection they offer;
   •   Individual differences in dermal exposure due to differing degrees of speed, care, and
       dexterity in performing work;
   •   Variance in the amount of material available for dermal absorption due to actions such as
       wiping the affected area with the hand;
   •   Variances  in the penetrability of the skin in different areas of the body;
   •   Individual variability of skin penetrability due to age of the individual and skin condition;
       and
   •   The matrix (liquid, solid, vapor) of the chemical contaminant.

       The amount of chemical coverage on the skin surface can influence the amount of dermal
absorption. Chemical coverage of the skin surface may be incomplete where only part of the
surface is covered or it may be complete where the entire skin surface is covered. In both cases
only the amount of chemical in contact with the skin surface is available for absorption such that
the capacity of the skin to absorb the chemical may be exceeded. This is particularly true for
cases of chemically contaminated solids such as soil where the material can pile up on the skin.
Likewise the transfer efficiency of a chemical from a contaminated surface or a liquid solution to
the skin may be highly variable due to the nature and extent of the contact, chemical composition
and its affinity for skin relative to the surface or media, or the deposition of chemical residue due
to evaporation of the liquid.  Additionally, actual exposures can be affected by both external and
personal characteristics, for example temperature,  humidity, the medium containing the
contaminant, the presence of other pollutants or inert ingredients in the medium, variations in the
amount of thickness of the exposed skin, or the degree of hydration of the skin.

1.3.    DERMAL ABSORPTION CONSIDERATIONS
       The skin is a highly complex organ that effectively performs a barrier function to protect
the body from a variety of environmental insults. Its structure and function has been extensively
described previously (Roberts and Walters, 1998).  Passive diffusion is considered to be the main
processes of dermal penetration of chemicals through the stratum corneum, the outermost layer
of the skin. After a chemical has absorbed into the stratum corneum it can pass through it into
the viable epidermis (the next skin layer) and then into the dermis where it can be transported

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systemically by the dermal blood supply.  Dermal penetration can be measured by in vivo or in
vitro methods.


1.3.1.  In Vivo Dermal Absorption Methods
       In vivo techniques can be used to measure dermal penetration either directly or indirectly
(Bunge and McDougal, 1999). In direct methods a chemical is measured in the blood or excreta,
on strips of tape that progressively remove stratum corneum, or estimated by biological or
pharmacological responses.  In indirect techniques dermal absorption is inferred from the
disappearance of the chemical from the skin surface. The following list describes several in vivo
methods used to estimate dermal absorption (Wester and Maibach, 1999):


   •   Surface recovery.  The amount of chemical remaining on the  surface of the skin at the
       end of the exposure is measured (recovered dose). The  absorbed dose is assumed to be
       the difference between the amount of chemical applied to the skin (applied dose) and the
       recovered dose.

   •   Surface disappearance. The disappearance of a compound from the surface of the skin is
       measured over  time using the appropriate instrumentation.  This method is limited
       because it does not measure the amount of the chemical that is absorbed into the skin.

   •   Measuring the total amount of chemical appearing in the excreta.  The chemical (often
       radiolabeled) is applied to the skin and the total amount excreted in the feces and urine is
       compared to the amount of excreted following a parenteral administration. When
       determined by radioactivity, this method does not account for dermal or systemic
       metabolism because the amount of radioactivity includes both parent compound and
       metabolites.

   •   Measuring the total amount of chemical in the blood. This is measured by the ratio  of the
       areas under the plasma concentration versus time curves following dermal and
       intravenous administration of the chemical.  When radiolabeled chemicals are used, this
       method does not account for dermal or systemic metabolism because the radioactivity
       could include both parent compound and metabolites, unless combined with methods that
       separate parent and metabolite.

   •   Biological and  pharmacological response. A biological assay is substituted for a
       chemical assay such that absorption is estimated by observing the magnitude of the
       biological response.  This method is limited to compounds that elicit responses that  can
       be measured easily.

   •   Tape stripping. This method determines the concentration of the chemical in the stratum
       corneum after a specified exposure time. The technique involves sequentially application
       of adhesive tape strips to the exposed site, after any remaining chemical on the skin
       surface is removed, until all of the stratum corneum is removed from the skin.
       Direct in vivo testing methods are more complicated and time consuming.  However,
they can provide estimates of the total absorbed amount of chemical in the blood or tissue and
the amount eliminated (Zendzian, 2000). For example, the in vivo protocol specified by OPP for

                                           4

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testing pesticides in the rat measures the amount of chemical in excreted material during the
exposure and the amount in the carcass at the end of the exposure (Zendzian, 1994, 2000).  In
addition, the amount of chemical remaining in the washed skin from the exposed site is
measured. Provided that the wash is 100% efficient, this amount combined with the amount in
the carcass and the excreted material should be the total amount dermally absorbed.  Indirect in
vivo techniques have been used successfully but there are some drawbacks. These techniques
can be used only for chemicals that are not volatile. However, pharmacokinetic modeling can be
used to estimate absorption from blood, exhaled breath, or tissue concentrations (Bunge and
McDougal, 1999).  The tape stripping method can be used to determine the amount of chemical
in the stratum corneum. Disadvantages of tape stripping method are: the stratum corneum must
be stripped completely and rapidly and chemical analysis can be difficult because the amount of
chemical recovered can be small.

1.3.2.  In Vitro Dermal Absorption Methods
       In vitro dermal absorption methods have appeal because they lack use of live animals, are
less expensive than in vivo methods, can be used with skin from a variety of animal species
(most notably human), and can be used to test toxic or corrosive chemicals without concern for
ethical considerations. Two different types of in vitro techniques have been used to study dermal
absorption, the infinite dose and finite dose technique (OECD, 2004; Sartorelli et al., 2000;
Franz, 1973). The infinite dose technique is the most frequently utilized method.  It involves
mounting the skin as a barrier between two chambers of fluid. A large amount of chemical,
usually in water or an aqueous solution is added on one side and absorption is quantified by
measuring the concentration in a receptor solution on the other side as a function of time.
Measurements are continued until steady state is achieved as indicated by the cumulative mass in
the receiving chamber increasing as a proportion to time.  The permeability coefficient is then
calculated using the slope of the linear regression of the cumulative mass versus time (Bunge and
McDougal, 1999).  In the finite dose technique, skin is mounted in a diffusion cell and bathed
from below by a receptor solution kept at a temperature of 37°C.  The donor chamber contains a
known amount of the chemical and the concentration of the penetrating chemical is measured in
the receiving chamber to provide a measure of the cumulative amount that has penetrated a
specified area of skin in a given exposure time (usually expressed as the percent absorbed per
square centimeter of skin exposed).  An advantage of the finite dose technique is that it allows
for any type  or amount of substance to be tested in conditions that mimic those encountered in
vivo (Sartorelli et al., 2000).
       One of the major factors affecting in vitro dermal penetration results is the choice of
receptor fluid for collecting the chemical that penetrates the skin. Generally, it should provide
sink conditions without altering the skin barrier function.  The current OECD guidelines require
that sink conditions be insured by proving adequate solubility in the receptor fluid (OECD,
                                           5

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2004). The receptor fluid should be chosen to maintain skin metabolic activity when fresh skin
is used and the absorbing chemicals may be metabolized.

1.3.3.  In Vivo/In Vitro Dermal Absorption Method Comparisons
       Efforts to compare in vivo and in vitro dermal absorption methods have generated mixed
results (Franz, 1975; Zendzian and Dellarco, 2003). In vitro methods may overestimate or
underestimate in vivo measurements depending on the nature of the chemical, the skin
preparation used, chemical vehicle used, experimental procedures followed and the data analysis
procedures used. In vivo measurements for exposure times that are not long relative to the time
to penetrate through the skin (lag time) will usually overestimate the steady-state permeability
coefficient because in vivo dermal absorption is initially faster than at steady state. Bunge and
McDougal (1999) concluded that this is consistent with the "widely stated observation that in
vivo permeability coefficients are larger than those measured in vitro." However this
observation may be  due to a failure to account for the lag time in data analysis rather than reflect
differences between in vitro and in vivo methods (Bunge and McDougal,  1999).
       The Percutaneous Penetration Subgroup (PPS) of the Dermal Exposure Network
published a report that focused on standardization and validation of in vitro experiments
(Sartorelli et al., 2000).  The objectives  of the PPS were to analyze the guidelines on dermal
penetration in vitro studies presented by various organizations and suggest standardized in vitro
methods while taking into account their individual research experience, literature data and
existing guidelines.  Key issues and data gaps reported by the subgroup included:

   •   How to use dermal penetration data in risk assessment;
   •   Factors influencing the results from dermal penetration in vitro studies (i.e., the choice of
       the donor phase, cell characteristics, skin membranes present, and receptor fluids);
   •   Agreement on and validation of existing guidelines for conducting in vitro  studies;
   •   Use of penetration data to predict plasma levels;
   •   Effects of cutaneous metabolism on dermal penetration;
   •   The selection of appropriate reference chemicals for in vitro study;
   •   Use of microdialysis in in vivo studies; and
   •   The correlation  of in vitro and in vivo study results.

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       2.  U.S. EPA APPROACHES TO DERMAL EXPOSURE ASSESSMENT

2.1.    OFFICE OF PREVENTION, PESTICIDES, AND TOXIC SUBSTANCES (OPPTS)
       Two offices in the Office of Prevention, Pesticides, and Toxic Substances (OPPTS)
address dermal exposure issues: the Office of Pollution Prevention and Toxics (OPPT) in their
regulatory and voluntary programs for new and existing industrial chemicals and consumer
products and the Office of Pesticide Programs (OPP) in their regulation of new and existing
pesticides.  Dermal exposure in these areas is assessed using a variety of models and tools for
specific situations.

2.1.1.  Office of Pollution Prevention and  Toxics (OPPT)
       The OPPT makes available on-line two PC-based tools: ChemSTEER and EFAST.
ChemSTEER is currently available in a Beta Version, which was released in late May 2004, and
EFAST is available in Beta Version 1.1, which was released in March 2000. They are accessible
on-line at http://www.epa.gov/oppt/exposure/.
       ChemSTEER allows screening-level  estimation of chemical releases from industrial and
commercial sources and operations, and estimation of worker exposures through inhalation and
dermal contact.  These estimates are derived from user input parameters and default parameters
based on industry data collected by EPA.  The beta version includes 34 models, each with a set
of default settings  and values.  Among the models for dermal exposures are one-hand liquid,
two-hand liquid, and mass-balance dermal exposure  models, as well as degree of "immersion" or
contact. All models assume that no protective equipment is used.  Four scenarios that address
multiple sources and activities for specific industries are currently incorporated in ChemSTEER:
exposure during adhesives formulation, during new and refinishing automobile spray-coating,
and water additives in recirculating water-cooling towers.
       The dermal models require selection  of an operation: manufacturing, processing, or use;
and an activity,  such as loading containers. The specific model is  chosen based on the activity.
One can view the model equation, the input parameters, the source of the model, the mechanism
of exposure, and the chemical state (for example liquid) of the subject chemical. Two daily
potential dose rate estimates, such as for typical and  high-end (worst-case) exposures,  can be
calculated and viewed simultaneously.
       User input parameters can include chemical name, chemical category, trade name,
Chemical Abstracts number, vapor pressure  (torr), molecular weight (g/mol), density (g/cm3),
water solubility (g/L), production and use volumes, weight fractions and physical states. In
addition, inputs can include numbers of sites, working days,  and workers; release sources and
worker activities; workplace concentrations and release amounts and media; and types and sizes
of containers used to transport the chemical or mixture.  Default parameters are incorporated in
the program for use if input data are not available. Some parameters cannot be changed. For
                                          7

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example, in the two-hand liquid loading model, the skin surface area S is set at 840 cm , and the
quantity Qu remaining on the skin is set at either 0.7 or 2.1 mg/cm2. Other parameters such as
body weight, weight fraction of active ingredient, exposure duration can be changed.  Similarly,
for the two-hand solid loading model or for direct contact with solids, the quantity S times Qu is
set at 3,100 mg/event, although other parameters in the model can be changed. The model
assumes that the quantity remaining on the skin or surface loading per event is not affected by
wiping off the  excess, nor do additional contacts increase the quantity significantly.
       An example of ChemSTEER estimates for the operation "adhesives formulation" and the
activity "loading liquid into drums" is:  default weight-fraction of active ingredient (ai) is 0.33,
work-life averaging time is 40 yr (lifetime is 70 yr), skin surface area is 840 cm2 (for the two-
hand model), and the body weight is 70 kg. In this  example, the surface loading selected is 2.1
mg/cm2, a high end estimate which is based on industrial data for this operation involving liquid
handling.  These parameters give a potential dose rate of 581 mg/d and an acute potential dose of
8.32 mg/kg-d.
       In the ChemSTEER user-defined input model, dermal exposures for liquid or soil contact
are calculated as the following:l

                                Dexp = S * Qu *  Yderm * FT
LADD =
                                    *     *
                                      ED * EY) / (BW * Ate * 365)
                       ADD = (Dexp * ED * EY) / (BW * AT * 365)
                                  APDR = (Dexp/BW)
                                                              (1)
where:
       Dexp       =  dermal potential dose rate
       LADD    =  lifetime average [potential] daily dose
       ADD      =  average [potential] daily dose
       APDR    =  acute potential dose rate
       S         =  skin surface area
       Qu        =  quantity remaining on skin
                    [surface loading per event]
       Yderm      =  weight fraction of chemical
       FT        =  event frequency
                                             (mg/d)
                                             (mg/kg-d)
                                             (mg/kg-d)
                                             (mg/kg-d)
                                             (cm2)
                                             (mg/cm2-event)
                                             (events/site-d)
       1 An asterisk (*) denotes multiplication throughout this document.

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       ED       =  days exposed per year                           (d/site-yr)
       EY       =  years of occupational exposure                   (yr)
       BW       =  body weight                                    (kg)
       Ate       =  lifetime averaging time for chronic exposure       (yr)
       AT       =  averaging time                                 (yr)

       EFAST allows screening-level estimation of consumer exposures through inhalation and
dermal contact, as well as estimation of industrial releases to air, landfills, and water.  The
outputs cover site-specific general population exposures to chemicals through ingestion of
drinking water and fish, and estimates of ecosystem risks through contamination of surface
waters. Human dermal exposures are estimated through selection from three pre-set consumer
product-related scenarios: application of products to hard surfaces, such as paint during
application; contact with chemicals added to water, such as detergents;  and direct contact with
products, such as motor oil. Consumer product scenarios include use of a general purpose
cleaner, use of liquid laundry detergent, use of bar soap, and changing motor oil.  User scenarios
can also be entered in the program.
       The EFAST Consumer Exposure Model (CEM) allows conservative estimates of
potential and absorbed dermal dose to chemicals in some consumer products, as well as
screening-level estimates of acute potential dose rates, and average and lifetime daily potential
dose rates. A film-thickness approach is used, which  assumes a thin film of product on a defined
skin area to determine exposure, but the uncertainty is great, as there are few supporting data on
film thicknesses on skin.  Film thickness values in the CEM are derived from experimental data
(Versar, 1992).  For exposure to chemicals in water, such as washing clothes by hand, the film
thickness is based on the initial film thickness of water on the hands after immersion in water;
for washing the body and/or hands with bar soap, it is based on the initial film thickness of a bath
oil/water mixture on the hands; and for changing motor oil, it is based on the thickness of a
mineral oil film on the hands after immersion.
       User inputs can include release information from the product to the environment, based
on activity, site, media, amount, and frequency; physical and chemical properties of the
pollutants  of interest; and fate  and transport properties. Users can also create their own scenarios
if a product does not fit into one of the pre-defined scenarios. The default parameters  are
generally those provided in the EPA Exposure Factors Handbook (EFH; U.S. EPA, 1997b). For
example, 50th percentile body weights are 71.8, 26.9, and 10.2 kg for an adult, a child, and an
infant, respectively. Averaging times (AT) for non-carcinogenic chemical exposures are 30 yr
for ambient and 57 yr for consumer product exposures of adults; for acute exposures of adults,
children, and infants, the AT is one day. The averaging time for carcinogenic chemical
exposures is 75 yr for all individuals. Because there is a direct relationship between an
individual's weight and skin surface area, the EFAST dermal exposure  model uses the surface

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area/body weight ratio (SA/BW).  Use of SA/BW may reduce bias that could occur if surface
area distributions were combined with unrelated body weight, for example if one were to
combine upper-percentile SA with lower-percentile BW.  Distributions of SA/BW can be
obtained from the EFH (U.S. EPA, 1997b, Table 6-9).
       Three different dermal exposure calculations can be performed: a lifetime average daily
potential dose (LADD), an average daily potential dose (ADD), and an acute potential dose rate
(ADR). The form of the general equation used to calculate potential dose is:

             Dose  =(Q* SA/BW * FQ * Y * WF * 1000 mg/g)/ (AT* 365)            (2)

where:
       Dose      =  daily potential dose                              (mg/kg-d)
       Q         =  amount retained on the skin                      (g/cm2-event)
                    [surface loading per event]
       SA/BW    =  surface area/body weight                         (cm2/kg)
       FQ        =  frequency                                      (events/yr)
       Y         =  years of use                                    (yr)
       WF       =  weight fraction of product
       AT        =  averaging time                                 (yr)

       Absorbed dermal dose rates can be calculated in user-defined scenarios, using a skin
permeability coefficient Kp specific to the given chemical, which may be chosen from a list of
common chemicals in the program, entered directly by the user, or calculated by the program
from the octanol/water partition coefficient (Kow).  In the program, Kp is calculated from the
following equation (U.S. EPA, 1992a):

                    log Kp = 0.71  * log Kow - 0.0061  * MW - 2.72                       (3)

where:
       Kp        =  permeability coefficient                          (cm/h)
       Kow       =  octanol/water partition coefficient
       MW      =  molecular weight                                (g/mol)

2.1.2.  Office of Pesticide Programs (OPP)
       The Office of Pesticide Programs uses several SOPs to estimate dermal exposures (U.S.
EPA,  1997a). These SOPs cover both commercial and residential pesticide applications.
Exposures resulting from direct contact with pesticides during application and contact with
treated surfaces  after application can be estimated for adults and children.  Updates to the SOPs,
                                          10

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including information on exposure frequency, are being developed by OPP.  The underlying
assumptions and definitions are available on line (U.S. EPA, 2000b, c, 1997a, Appendix A).
Occupational dermal exposure issues are addressed by the PHED surrogate table and guidance
document policy 12.  An evaluation of exposure assessment methods for agricultural pesticide
workers was recently presented to the Scientific Advisory Panel (U.S. EPA, 2007c).
       The residential SOPs rely on high-end scenarios that are assumed to represent the upper
end of the distribution of exposures that could occur in residential settings. They have the
flexibility to be used as a screening tool but can be refined based on the availability of chemical
and scenario data and the interest of the user. They rely on one or more upper-percentile
assumptions such as the 90th percentile skin surface area values or exposure durations. Each
SOP includes a description of the exposure scenario, recommended methods for quantifying
dose, example calculations, the limitations and uncertainties associated with the use of the SOP,
and relevant references. Pesticide handler and post-application SOPs are provided for pesticide
applications in several residential scenarios. Each provides methods for estimating short-term or
acute daily doses for a single route of exposure (inhalation, ingestion, dermal absorption).  Those
that include dermal methods are scenarios for exposure during application and post-application
contact to pesticides applied to lawns, gardens,  trees, swimming pools, and pets; to paint and
wood preservatives; and to rodenticides. Other SOPs address dermal exposures to pesticides
during and after crack-and-crevice and broadcast applications; to pesticides in detergents and
hand soap; and to pesticides in impregnated materials. Use of products according to label
directions is assumed.  Several SOPs rely on field monitoring data from the PHED, the Outdoor
Residential Exposure Task Force, or other studies that are available, including studies in the
scientific literature, to estimate handler exposures.
       In all cases, the dermal potential dose rate is normalized to body weight by dividing the
potential dose rate (PDR) by the body weight BW in kg to give the potential dose, with the body
weight chosen to fit the specific population of individuals:

                             Dose = PDR / BW        (mg/kg-d)                      (4)

       Pesticide handler: Daily potential dose rates are calculated using equations of the
following form:

                                      PDR = UE *  AR * A                            (5)
                                           11

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where:
       UE       =   unit exposure
       AR       =   maximum application rate
       A         =   maximum area treated
                                                (mg/lb ai)
                                                (Ib ai/acre or Ib ai/gal)
                                                (acre/d or gal/d)
This calculation gives the maximum potential dose rate.
       Transfer of residues from treated surfaces:  Dermal potential dose rates on post-
application days are calculated as follows:
                                  PDRt = DFRt * CF1 * Tc * ET
                                                                  (6)
where:
       PDRt
       DFRt
       CF1
       Tc
       ET
potential dose rate on day t
dislodgeable (transferable) residue on day t
conversion factor
transfer coefficient
exposure time
(mg/d)
(ug/cm2)
(0.001 mg/ug)
(cm2/h)
(h/d)
and
                               DFRt = AR * F * (1-D)1 * CF2 * CF3)
                                                                  (7)
where:
       AR
       F
       D
       t
       CF2
       CF3
application rate (of active ingredient)
fraction of ai retained on surface
fraction of residue that dissipates daily
post-application day
conversion factor2
conversion factor
(Ib ai/ft2 or Ib ai/acre)
(4.58E8 ug/lb)
(1.08E-3ft2/cm2or
24.7E-9 acre/cm2)
       An appropriate dermal absorption factor can be used, if available, to estimate absorbed
dose. Most of the SOPs (U.S. EPA, 1997a) assume that 50% of the application to treated
surfaces is available initially as transferable residues on the day of application. It is important to
note that in some cases such as turf, DFR is replaced by transferable residue which is determined
       2The abbreviation E followed by a numeral denotes a power of 10, e.g., 4.58E8 is equivalent to 4.58
times 10".
                                            12

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from the Turf Transferable Residue method based on roller methods, foliar washes and other
techniques (U.S. EPA, 1999).
       Lifetime average daily dose: For exposures over a lifetime, which are relevant to cancer
and other health effects that may result from chronic exposure, the lifetime average potential
daily dose is calculated as follows:
                               LADD = (D * EF * ED) / (AT * CF)
                                                                  (8)
where:
       D
       EF
       ED
       AT
       CF
dose [potential daily dose]3
exposure frequency
exposure duration
averaging time
conversion factor
(mg/kg-d)
(d/yr)
(yr)
(yr)
(365 d/yr)
       Handler exposure to chemicals in treated water in swimming pools: The potential dose
rate is calculated as:
                                   PDR = UE * AR* V
                                                                  (9)
where:
       UE       =   unit exposure
       AR       =   maximum application rate
       V        =   maximum volume treated
                                                (mg/lb ai)
                                                (Ib ai/gal)
                                                (gal/d)
       Swimming post-application of pesticides: The dermal absorbed dose rate from
swimming in areas treated with pesticides post-application is calculated as:
                            ADR = Cw * SA * ET * K * CF1
                                                                 (10)
where:
       ADR
       ^W
       SA
       ET
absorbed dose rate
concentration of ai in the water
skin surface area exposed
exposure time
(mg/d)
(mg/L)
(cm2)
(h/d)
       3The symbol D in the residential SOP document (U.S. EPA, 1991 a) is used both for the daily fractional
dissipation of surface residue in estimating exposure to pesticides on surfaces and for the daily dose in estimating
lifetime average daily dose.
                                            13

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CF1
                 =   skin permeability coefficient
                 =   conversion factor
(cm/h)
(L/1000 cm3)
       Applications of paint or stain in residential settings: Handler dermal potential doses from
painting or staining in residential settings assume a single daily event and do not include
exposure duration. Therefore these doses are based on the amount of active ingredient handled
per day. Unit exposure values from PHED can be used.  The calculation is of the form:
                                    PDR = UE * AR * N
                                                                              (11)
where:
       UE
       N
             unit exposure
             number of cans applied
(mg/lb ai applied)
(cans/d)
and
                                    = V*n*(P/100)*CFl
                                                                              (12)
where:
       AR       =  active ingredient applied per can
       V         =  paint volume per can
       fi         =  specific gravity of paint
       P         =  percent by weight of ai in paint
       CF1       =  conversion factor
                                                             (Ib ai/can)
                                                             (mL/can)
                                                             (g/mL)

                                                             (2.2E-3 Ib/g)
       Crack-and-crevice or broadcast applications:  Estimates of potential doses of pesticides
during crack-and-crevice or broadcast applications rely on surrogate PHED data, and are
calculated similarly to those for the paint/stain scenario. Post-application dermal doses of
pesticides on carpets are estimated assuming: an average of 50% of the application is available
as dislodgeable residue, chemical-specific daily dissipation rates, exposure duration 8 h/d, and
dermal transfer coefficients of 43,000, 8,700, and 6,000 cm2/h for adults, toddlers, and infants,
respectively. Post-application dermal potential dose rates are calculated as follows:
                               PDRt = ISRt * CFlt* Tc * ET
                                                                              (13)
where:
       PDRt     =  potential dose rate on day t
       ISRt      =  indoor surface residue on day t
                                                             (mg/d)
                                                             (ug/cm2)
                                           14

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       CF1       =   conversion factor                                (0.001 mg/ug)
       Tc        =   transfer coefficient                              (cm2/h)
       ET        =   exposure time                                   (h/d)

and

                             ISRt = AR*F * (1-D)1 * CF2 * CF3                       (14)

where:
       AR       =   application rate                                 (Ib ai/ft2)
       F         =   fraction of ai retained on surface
       D         =   fraction of residue dissipated daily
       t          =   post-application day
       CF2       =   conversion factor                                (4.54E8 ug/lb)
       CF3       =   conversion factor                                (1.08E-3 ft2/cm2)

       For exposure to residues on hard surfaces, such as hard floors or counter tops, the same
equations are used, but the exposure duration is assumed to be 4 h/d, rather than 8 h/d.
       Applications of pesticides to pets:  Dermal doses to individuals who treat pets with
pesticides for vermin control are based on the amount of active ingredient handled per day and a
single treatment per day, as for paint and stain applications. The default fraction of the active
ingredient (F) available for exposure is 10%, except for flea collars, which it is  1%.  Thus the
potential dose rate is:

                                     PDR = AR*F                                  (15)

where:
       AR       =   application rate                                 (mg/d)
       F         =   fraction of active ingredient available              (0.1  or 0.01)

       Spray applications of pesticides to pets: The amount handled per treatment is assumed to
be the maximum available on the label, or 1A can.  Unit exposure values from PHED for typical
aerosol applications of pesticides are used. The potential dose rate is calculated as:

                                  PDR = UE*AR*N                               (16)

where:
       UE       =   unit exposure                                   (mg/lb ai)
                                            15

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       N         =  number of cans used                            (cans/d)

and
                                  = V*n*P/100*CFl                              (17)

where:
       AR       =  active ingredient per can                         (Ib ai/can)
       V         =  liquid volume of spray per can                    (mL/can)
       fi         =  specific gravity of spray solution                 (g/mL)
       P         =  percent by weight of active ingredient
       CF1       =  conversion factor                               (2.2E-3 Ib/g)

       Pesticide residues on pets: It is assumed that 20% of the application is retained on the pet
as dislodgeable residue, 10% of the residue is transferred during contact with a treated animal,
one animal is contacted per day, and that there is no dissipation of the residues on subsequent
days.  The dermal potential dose rate for liquid applications is

                                   PDR = AR*F*T                                (18)

where:
       AR       =  active ingredient applied                         (mg ai/d)
       F         =  fraction of ai available
       T         =  fraction of residue transferred to skin

       Note that these SOPs provide a standard  method for estimating potential doses that
homeowners may receive during pet treatment from inhalation and dermal contact when
chemical specific  data are unavailable. This scenario assumes that pesticide exposure occurs
while applying the pesticide to pets using aerosol spray products. The method to determine
handler inhalation and dermal dose from pesticides while treating pets relies on using surrogate
PHED data and does not apply to  livestock. Thus, these methods are used when actual field data
are not available or as a supplement to estimates based on field data.
       Pesticides  in soaps, detergents, and other consumer products:  Handler and post-
application exposure can be estimated with a screening model, DERMAL (U.S. EPA,  1995),
which covers 16 types of consumer products, and can accommodate user inputs for other
products. The model is said to calculate dermal  exposure using the weight fraction of the
chemical in the product, assumed  film thicknesses  on the skin, and assumed exposed skin area.
Default values are used for the event frequency,  exposure duration, and body weight. The
EFAST Consumer Exposure Model, mentioned above, includes DERMAL.
                                          16

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       Materials impregnated with pesticides: Exposures from contact with materials
impregnated with pesticides, including paint and stain post-application on surfaces, are estimated
based on the flux rate through the material of interest and the skin area that is likely to be
contacted. An EPA guidance document allows estimation of the flux rate (U.S. EPA, 1992c).
The skin surface area depends on the product, for example, 1 m2 and 0.35 m2 for plastic mattress
contact of adults and toddlers, respectively. The duration of exposure is likewise dependent on
the specific activity and material. The potential dose rate is calculated as:

                                 PDR = FR* SA*ET*CF1                          (19)

where:
       FR       = flux rate for the product of concern                (mg/m2/d)
       SA       = skin surface area                                (m2)
       ET       = exposure time                                   (h/d)
       CF1       = conversion factor                                (d/24 h)

       An additional SOP covers the  pesticide exposures of individuals in the post-application
scenario of "pick-your-own" strawberries. It is assumed that 20% of the application is available,
exposure time is 2 h, and dermal transfer coefficients are 10,000 cm2/h for adults and 5,000
cm2/h for youth ages 10 to 12.  Potential dose rates are calculated similarly to those for contact
with other treated surfaces.
       The OPP has developed a tool that deals with the risk from the inert ingredients in
pesticide products.  A test version (V  1.0) of this screening tool, Pesticide Inert Risk Assessment
Tool (PIRAT), is available on-line (U.S. EPA, 2007d). In PIRAT, one selects handler or post-
application exposures, dermal or inhalation, formulation, duration, and carrier.  One also selects
the product use category and the application method.  The weight fraction of product (inert
ingredient) depends on  the formulation selected.  PHED unit exposure values are incorporated.
Toxicity and absorption values can be entered if known. Post-application dermal exposures can
be estimated for adults  and toddlers (age 3 yr), assuming the fraction of skin area exposed is
0.05, the transfer coefficients are  14,500 cm2/h for adults and 5,200 cm2/h for toddlers,  and the
body weights are 70 kg for adults and 15 kg for toddlers.  PIRAT provides screening-level
estimates of exposure and risk associated with the use of pesticides in residential settings, both
indoors and outdoors.  Acute and chronic risk assessments for adults and children are to be
provided separately.
                                           17

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       The form of the equation for the potential dose rate4 for handler exposure in PIRAT is
given as

                           PDR = (UE* AR*WF* A* ABS)/BW                   (20)

where:
       PDR      =  potential dose rate                         (mg/kg/d)
       UE       =  PHED Dermal Unit Exposure              (mg/lb)
       AR       =  application rate                           (lb/ft2; gal/d; Ib/gal; mg/d)
       WF       =  weight fraction
       A         =  area treated or amount used                (ft2/d; gal/d)
       ABS      =  percent absorption value                   (%)
       BW       =  body weight                              (kg)

2.2.    OFFICE OF SOLID WASTE AND EMERGENCY RESPONSE (OSWER)
       Within OSWER, the Office of Superfund Remediation and Technology Innovation
(OSRTI) has developed guidance to address dermal exposures to toxic chemicals that result from
contact with either contaminated water or contaminated soil for both adults and children from
hazardous waste sites (U.S. EPA, 2004a). It incorporates the ingredients of the Agency guidance
document, Dermal Exposure Assessment: Principles and Applications (U.S. EPA, 1992a) and
includes several dermal exposure equations, tables of screening values for exposure to
contaminated water, absorption values for contaminants from soil, soil adherence factors, and
parameters that are consistent with the U.S. EPA Exposure Factors Handbook (U.S. EPA,
1997b).
       Recommended default exposure values are presented in RAGS E for the dermal-water
and dermal-soil pathways. In general, to estimate exposure to an average individual,  the 95%
upper confidence limit on the arithmetic mean is chosen for the exposure point concentration,
and central estimates, such as arithmetic mean, 50th percentile, etc., are chosen for all other
exposure parameters. The reasonable maximum exposure (RME) values are the highest
exposures that might reasonably be expected at a given site.  Central tendency values can also be
calculated.
       For dermal exposure to contaminated water, only those chemicals that  contribute more
than 10% of the dose that may occur from water ingestion are considered sufficiently important
to carry through a risk assessment (U.S. EPA, 2004a, Chapter 6). Predicted values of the skin
permeability coefficient Kp (cm/h) are given for 19 metals and more than 200 organic pollutants.
       4In PIRAT, PDR is defined as the potential dose rate. This differs from the definition of PDR in the
equations discussed in other sections of this document, as it includes the body weight BW and therefore refers to the
potential dose.
                                           18

-------
The Kp values are updated from those given in the DEA, but are limited to only those in vitro
studies using human skin. Kp is estimated with an empirical correlation, which is a function of
the octanol-water partition coefficient Kow and molecular weight for about 90 chemicals,
obtained from an experimental  database on absorption of chemicals from water through human
skin in vitro.  These Kp values are then used in default scenarios to estimate exposures from
contact with contaminated water.  Dermal absorbed dose (DAD) values for several hundred
chemicals through the water pathway, based on the default exposure scenarios, are provided.
       The skin surface area used in calculating dermal-water exposures is based on EFH values
and assumed to be the entire  skin surface for swimming and bathing. In calculating dermal-soil
exposures, the default skin surface area for adults in non-occupational (residential) settings
includes the head, hands, forearms, and lower legs; in occupational settings it includes the head,
hands, and forearms.  For children, ages 0 to 6, the default skin surface area includes the head,
hands, forearms, lower legs, and feet.
       The dermal absorbed  dose that results from contact with organics in contaminated water
is calculated as:
                        DAD = (DAevent * EV * ED * EF * SA) / BW * AT              (21)

where:
       DAD     =  dermal absorbed dose                            (mg/kg-d)
       DAevent    =  absorbed dose per event                          (mg/cm2-event)
       SA       =  skin surface area available for contact              (cm2)
       EV       =  event frequency                                 (events/d)
       EF        =  exposure frequency                              (d/yr)
       ED       =  exposure duration                               (yr)
       BW       =  body weight                                    (kg)
       AT       =  averaging time                                  (d)

       The parameter DAeVent is a function of several chemical-specific and site-specific
parameters: the dermal permeability coefficient Kp, the concentration in the water Cw, the lag
time per event tevent, the event duration, the time to reach steady state, and the ratio of the
permeability coefficient through the stratum corneum to the permeability coefficient across the
viable epidermis.  The model assumes that absorption continues after exposure,  depending on the
specific chemical.  DAevent is estimated to be the total dose dissolved in the skin when steady
state is reached. For highly lipophilic chemicals or for chemicals that are not highly lipophilic,
but for which tevent is long, an additional parameter, fraction absorbed (FA), the net fraction
available for absorption after exposure has ended, is included in DAeVent to account for losses of
the chemical due to desquamation.  For normal desquamation, the stratum corneum is completely
                                           19

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replaced in approximately 14 days.  Therefore FA is considered to be important only for those
chemicals with log Kow >3.5 or for tevent >10h. Default values for several of these parameters are
given in RAGS E (U.S. EPA, 2004a). The screening procedures include updated values for Kp
and FA, for use when the dermal dose is likely to provide more than 10% of the dose from
ingestion.
       For contact with inorganics or highly ionized organics in water,

                              DAevent = Kp * Cw * tevent                                (22)

where:
       Kp        =  dermal permeability coefficient                  (cm/h)
       Cw        =  concentration in water                           (mg/cm3)
       tevent      =  event duration                                  (h/event)

       The value of Kp for inorganics ranges from 6E-4 to 2E-3 cm/h for metals, except mercury
vapor, for which Kp is 0.24 cm/h. For all other inorganics, the Kp is given as 1E-3 cm/h.
Screening procedures are included in RAGS E (U.S. EPA, 2004a) to drop estimation of dermal
absorption of inorganics which do not exceed 10% of the ingested dose, when the fraction
absorbed from the gastrointestinal tract has been estimated or quantified.
       Few dermal absorption values for specific chemicals are available for estimating dermal
exposures from contact with contaminated soil.  The guidance document provides dermal-soil
absorption values (ABSd) for ten pollutants: As, Cd, and a few chlorinated organic compounds.
Recommended experimental mean values of ABSd, taken from published studies, range from
0.001 to 0.25, with a default value of 0.1 for semivolatile organic compounds. No screening
values for inorganic compounds are provided. Dermal exposure to soils is considered to be more
significant than direct ingestion only for those chemicals that have a soil absorption fraction
exceeding 10% (U.S. EPA, 2004a, Chapter 6).
       Soil to skin adherence factors (AF) are provided for a variety of exposure scenarios. For
adult RME in residential settings, a high-end soil contact activity such as gardening leads to the
default AF = 0.07 mg/cm2. For child residential exposures, average exposures while playing
both in dry and wet soil lead to the default AF = 0.2 mg/cm2. For adult occupational exposures,
the central tendency and high contact assumption lead to the default AF = 0.2 mg/cm2. Activity-
specific AF values  are given for children and adults in several residential and commercial
settings, such as indoor and outdoor play, sports, construction work, and farming.
       The dermal absorbed dose that results from contact with chemicals in contaminated soil
is calculated using the same equation as the one for dermal absorbed dose for organics in
contaminated water. For exposure to chemically contaminated soil however, the parameter
                                           20

-------
     nt is a function of chemical and site-specific parameters: the concentration in the soil, an
adherence factor of soil to skin, and the dermal absorption fraction ABSd.
                            ant = Csoii * CF * AF * ABSd                              (23)

where:
       DAevent    =  absorbed dose per event                          (mg/cm2-event)
       CSoii       =  chemical concentration in soil                     (mg/kg)
       CF        =  conversion factor (10-E6 kg/mg)
       AF        =  adherence factor of soil to skin                    (mg/cm2-event)
       ABSd     =  dermal absorption fraction

       Dermal exposures to chemicals present in air are considered unlikely, in most cases, to
provide more than 10% of aggregate exposure.  Therefore methods for assessing dermal
exposure to chemicals in the vapor phase are not presented in the RAGS E document, and it is
assumed that inhalation is the major route of exposure for vapor-phase chemicals (U.S. EPA,
2004a, Chapter 6).  Exposure parameters for contaminated sediment and dermal toxicity to the
skin at the site  of contact are not addressed in RAGS E.

2.3.    OFFICE OF WATER (OW)
       The Safe Drinking Water Act, as amended in 1986, requires U.S. EPA to publish a non-
enforceable health-based "Maximum Contaminant Level Goal" (MCLG) and an enforceable
"Maximum Contaminant Level" (MCL), to establish the safe level of each regulated contaminant
in drinking water. The MCLs for various contaminants, published in the National Primary
Drinking Water Regulations, were developed taking effects on health, treatment technologies,
and economic impact into consideration. The MCLs apply to public water systems.  Under the
Clean Water Act, OW also publishes Human Health Ambient Water Quality Criteria for
Protection of Human Health from exposure to ambient water including fish and water
consumption. The media of OW's interest are therefore drinking water and ambient water.
       Currently OW calculates risk from contaminants associated with drinking water exposure
by assuming a 2 L/d drinking water ingestion rate, which is roughly at the 86th percentile of the
water ingestion rate of the U.S. population (U.S. EPA, 2004e).  The contribution from exposure
to drinking water relative to exposures from other media (e.g., food, air, soil) is then factored
with a Relative Source Contribution factor in the final MCLG derivation. OW is in the process
of evaluating different methodologies to estimate the extent of dermal and inhalation exposures
from various activities involving drinking and ambient water use, such as showering, bathing, or
dishwashing.
                                          21

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2.4.    OFFICE OF RESEARCH AND DEVELOPMENT (ORD)
       Various exposure research studies are conducted by the National Center for
Environmental Assessment (NCEA), the National Exposure Research Laboratory (NERL), and
the National Health and Environmental Effects Research Laboratory (NHEERL). Some of these
studies investigate dermal exposure methods and models (Geer et al., 2004; Morgan et al., 2004;
Wilson et al., 2004; Zendzian and Dellarco, 2003). Results of these investigations are published
in the scientific literature and incorporated into Agency guidance.  The Human Exposure
Database System (HEDS) contains human exposure study information and the Consolidated
Human Activity Database (CHAD) contains activity data useful in estimating exposures (U.S.
EPA, 2007e; McCurdy et al., 2000).  Both can be accessed through U.S. EPA's  Environmental
Information Management System (http://www.epa.gov/eims/).
       Additionally, the Stochastic Human Exposure and Dose Simulation (SHEDS) model
(Zartarian, 2003) and the Exposure Reconstruction and Dose Estimation Model  (ERDEM) are
under development in NERL.  Both can deal with transfer coefficient and loading data with
chemical-specific permeability coefficient inputs.
       SHEDS uses a probabilistic approach to predict the distribution of exposures and dose for
specified routes in a specific population. The model is designed to estimate this distribution by
simulating the time series of exposure and dose for individuals that demographically represent
the population  of interest. U.S. census data are used to build the simulation population, and
human-activity-pattern data are assigned to each simulated individual to account for the way
people interact with their environment. Pollutant concentrations in the microenvironments where
people spend their time (e.g., home, car, office, school, restaurant) are calculated based on
concentrations obtained from measurement study data or simulation. Each individual's exposure
and dose profile is estimated from the time spent in each location, the concentration in that
location and the activity-specific inhalation rate while in that location.  Daily-averaged exposure
and dose for each individual are calculated and combined to provide a distribution of exposure
and dose for the population. Statistical methods for incorporating both variability and
uncertainty in the model input parameters are utilized to obtain the predicted population
distribution and the uncertainty associated with the predicted distribution.  The model framework
has been developed for air toxics and for pesticides.
       There are two types of dermal exposure modeled in ERDEM, one for a chemical in an
aqueous vehicle, most often a water based diluent, and a chemical as a dried residue or adsorbed
onto particles as a dry source.  Skin surface exposure due to a chemical in an aqueous vehicle
may be input as a time history of time, the surface area of the skin (square centimeters) that
becomes exposed to the chemical, and the concentration (mass per unit volume) of the chemical
in the vehicle.  This concentration and area of the skin are used to compute the rate of change of
the amount of chemical absorbed. Linear interpolation is used to obtain intermediate values.  A
chemical residue existing on a surface is represented as a mass per unit area. It  is transferred to
                                           22

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the skin of a subject represented by a transfer coefficient.  A short exposure period would
represent a bolus that can accommodate loss due to evaporation and penetration through the skin.
The target populations modeled to date are primarily consumers; adults and children in
residential settings.
                                            23

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             3.  DERMAL EXPOSURE ASSESSMENT COMPARISONS

       The results of this study show that Agency program offices focus their efforts to
characterize and assess dermal exposure to media and scenarios according to their regulatory
mandates and responsibilities.  Consequently each office relies on different assumptions about
body weight, exposed skin area, length of exposure time and frequency of exposure events to
meet their specific needs. These differences are reflected in the methods they use to estimate
dermal penetration and in the specific guidance documents and tools and techniques they use to
conduct dermal exposure assessments. All program offices define dermal transfer as
mass/duration/area or volume or weight (e.g., ug/hr/cm2 or cm3 or kg) to indicate the amount of
chemical (mass) transferred from one medium to the receptor over unit time (hr or day) and  area
or volume or weight (cm2 or cm3 or kg).  Key differences reside in the description of the dermal
transport process itself in terms of infinite or finite source of media, steady state versus unsteady
state, Kp estimated from in vitro dermal absorption tests or estimates of an absorption fraction
from in vivo studies  and consideration for applied or absorbed dose with 100% absorption
assumption sometimes applied to dose calculation.  These similarities and differences among
these procedures are described below and represent potential areas for harmonization to improve
the consistency and transparency of dermal exposure assessments used in the Agency.

3.1.    TARGET POPULATIONS, EXPOSURE MEDIA, AND EXPOSURE
       PARAMETERS FOR DERMAL EXPOSURE ASSESSMENTS
       The target populations, exposure media, and exposure parameters currently used by the
EPA offices for dermal exposure assessments are summarized in Tables  1-3.  These tables can be
used to identify major pathways and the data input needs to assess dermal exposure. It shows the
complexity associated with the characterization and assessment of this route of exposure.

3.1.1.  Target Populations
       As summarized in Table 1 target populations for dermal exposure assessment comprise
both workers and consumers. Consideration is given to gender differences, to age groups for
consumer exposures, and to exposure associated with bathing and swimming. Parameters for
both age groups and skin area exposed are different among U.S. EPA Offices. Exposure to
workers addresses whole body exposure and exposure to particular body parts such as one or two
hands.  Generally body weight for workers is assumed to be 70 kg though OPP uses a mean  of
71.8 kg for male  and female  occupational and residential pesticide handlers. Consideration is
given to gender differences for total exposed skin area though  inconsistently so.  In some cases
total exposed skin area estimates are provided for males and females as in the OPPT PIRAT
(19,400 cm2 males and 16,900 cm2 females). In other cases total surface area estimates are
                                          24

-------
            Table 1. Target populations and assumed characteristics for dermal exposure assessment
EPA Office
OPPTS:
Chem-
STEER
OPPTS:
EFAST
OPPT:
PIRAT
OPP
Target
population
Workers
Consumers
Handlers and
Consumers
Occupational
and residential
pesticide
handlers
Consumers;
general
population
Assumed characteristics
Age and sex
Adults
Adults
18-75yr
Children
2-17 yr
Infants 0-2 yr
Adults
Toddlers 3 yr
Adults, 18yr
and older
Infants,
0.5-1. Syr
Toddlers,
Syr
Body weight
70kg(1541b)
71.8 kg, mean
for males and
females (EFH)
26.9 kg (EFH)
10.2 kg (EFH)
70kg
15kg
71.8 kg, mean
for males and
females
10kg
15kg
Skin area/exposed skin area
Total 18,150cm2
(average of males and females);
One hand, 420 cm2; two hands, 840 cm2
Total 19,400 cm2 (males),
16,900 cm2 (females);
Surface area/body weight
(SA/BW) 286 cm2/kg;
Two hands 840 cm2
(EFH 50th percentile values)
SA/BW 422 cm2/kg, age 2-17 yr (EFH)
Total <5,790 cm2 age <2 yr;
SA/BW 617 cm2/kg, ages 0-1 yr (EFH)
Total 19,400 cm2 (males), 16,900 cm2 (females); Fraction
exposed 0.05
Total 6,640 cm2 (males), 6,490 cm2 (females); Fraction
exposed 0.05
Total 19,400 cm2 (males), 16,900 cm2 (females);
Default areas for bathing/swimming 20,000 cm2;
outdoor soil contact 5,000 cm2
Total <6,030 cm2 (males), <5,790 cm2 (females) (EFH)
Total 6,640 cm2 (males), 6,490 cm2 (females),
hand 3 50 cm2
to

-------
            Table 1. Target populations and assumed characteristics for dermal exposure assessment (continued)
EPA Office
OPP
(continued)
OSWER:
Superfund
OW
ORD
Target
population
Consumers;
general
population
(continued)
Workers
Consumers;
residential
settings
Individuals in
non-
occupational
settings
Individuals in
non-
occupational
settings
Assumed characteristics
Age and sex
Children,
6 yr
Youth,
10-12 yr
Females
13-54 yr
Adults 18yr
and older
Adults
>18yr
Adults >1 8
Children
l-6yr
Adults and
children
Adults and
children
Body weight
22kg
39.1kg
60 kg (when
considering
reproductive
effects)
71.8kg
70kg
70kg
15kg
70kg
10kg
EFH values;
individual
measurements
Skin area/exposed skin area
Total 8,660 cm2 (males), 8,430 cm2 (females);
Default area for swimming/bathing 9,000 cm2
Total 12,000 cm2 (males), 12,400 cm2 (females)
Total 14,800 to 16,300 cm2
Total 19,400 cm2 (males), 16,900 cm2 (females);
Default area for swimming/bathing 20,900 cm2
3,600 cm2; head, hands and forearms exposed
Swimming or bathing: 6,600 cm2; Other: 2,800 cm2; Head, hands,
forearms, lower legs, feet exposed
Swimming or bathing: 6,600 cm2; Other: 2,800 cm2; Head, hands,
forearms, lower legs, feet exposed
Showering, bathing, dishwashing (drinking water); Swimming (ambient
water)
EFH values and individual measurements
to

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            Table 2.  Exposure media considered for dermal exposure assessment
EPA Office
OPPTS:
ChemSTEER
OPPTS: EFAST
OPPT: PIRAT
OPP
OSWER: Superfund
OW
ORD
Exposure media
Liquid industrial and commercial products and
intermediates
Liquid or solid consumer products applied to hard
surfaces, added to or used in water, or contacting skin
directly
Water, soil, treated surfaces (turf, foliage, pets); liquid
and solid formulations
Liquid and solid (granular, powder) formulations; treated
surfaces; paint/stain; impregnated materials
Soil, water, sediment
Water
All environmental media, including indoor and outdoor
air, water, soil, house dust, and surface residues; some
consumer products
Comments
Workplace release and exposure estimation for
new chemicals; several models or four
comprehensive industry-specific scenarios;
release estimates can be used as inputs to EFAST
Screening estimates of consumer dermal
exposures; three default scenarios
Screening estimates of handler and post-
application dermal exposures. Incorporates
PHED data
Standard operating procedures cover handler and
post-application exposures
Worker and consumer exposures to soil and
water at Superfund sites
Primary interest in general population dermal
exposure from water uses
Research emphasis on aggregate (all routes and
pathways) and cumulative (all chemicals with
similar modes of action) exposures
to

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            Table 3. Assumed and default exposure parameters for target populations for dermal exposure assessment

EPA
Office
OPPTS:
Chem-
STEER




OPPTS:
EFAST






OPPT:
PIRAT



OPP






Characteristics
-34 models with 4 specific occupational scenarios; AT
40 yr work-life; Ate 70 yr lifetime; ED 22 da/site-yr;
EY 40 yr; FT = 1 event/site-da; Default weight fraction
ai 0.33. For direct solids contact, S*Qu is constant at
3100 mg/event; for contact with solids containers,
S*Qu is 1 100 mg/event. Parameters based on industrial
data supplied to U.S. EPA.
Three specific consumer product exposure scenarios.
AT 30 yr for ambient exposures; Adult AT 57 yr for
non-carcinogenic consumer products; AT 1 d for acute
exposures; AT 75 yr for carcinogenic products.
SA/BW assumes both hands exposed (hand-washing
clothes), palms only (changing motor oil); whole body
and/or hands (bar soap use). Parameters based on
industrial data supplied to U.S. EPA.
Screening estimates for handler and post-application
exposure to inert ingredients, residues on turf, foliage,
pets. Formulation, application method, carrier selected.
Toxicity values can be entered. PFLED data
incorporated.
Handler exposures generally based on amount of ai
applied, e.g., residential turf handler exposure on
application day assumes one event/d, 20,000 ft2 treated,
5 gal spot treatment with specified ai; gardener handler
10,000 ft2 treated, 5 gal spray.


Skin areas
One hand
420, two
hands 840
cm2



Surface
area/body
wt ratio
SA/BW
(cm2/kg)



See Table 1




Not used




Skin loading,
adherence
factor
Constant at
0.7 (low) or
2.1 (high)
mg/cm2-event
for liquids


Amount
retained on
skin Q
(g/cm2-event);
based on
experimental
film thickness
data
Not used




Not used





Dermal
absorption
100%
absorption of
substance
available to
skin


Permeability
coefficient Kp
(cm/h) values
listed for
specific
chemicals


User can enter
absorption
coefficient


Not used





Transfer
coefficients
Not used






Not used







14,500
(adults), 5,200
(toddlers)
cm2/h

Not used




to
oo

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             Table 3.  Assumed and default exposure parameters for target populations for dermal exposure assessment
             frnntinnpH^
(continued)
EPA
Office


Characteristics
Contact with residues on treated surfaces assumes 20%
of application is available as transferable (dislodgeable)
residues on day of application; duration 0.33 h/d
(toddlers), 0.67 h/d (adults). A rate of dissipation from
surfaces is included, except for pet applications, which
are assumed to be steady state.
Indoor transferable residues post-application: high end
from carpet 50% of application, duration 8 h/d; from
hard surfaces 50%, exposure duration 4 h/d. A rate of
dissipation is included.
Skin areas
Exposed
skin areas
see Table 1
Exposed
skin areas
see Table 1
Skin loading,
adherence
factor
Not used
Not used
Dermal
absorption
Not used
Not used
Transfer
coefficients
43,000 (adults
high end),
10,000 (adults
typical), 5,000
(youth 10-12
yr), toddlers
(high end)
8,700 cm2/h
High end see
above.
Central 6,000
(toddlers),
16,700
(adults) cm2/h.
to
VO

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       Table 3. Assumed and default exposure parameters for target populations for dermal exposure assessment
       frnntinnpH^
(continued)

EPA
Office
OSWER:
Superfund












OW

ORD






Characteristics
Default values for dermal-water and dermal-soil
pathways. Dermal absorbed dose values for several
hundred chemicals from water, based on exposure
scenarios. Reasonable maximum exposure (RME)
values and central tendency values are calculated.
Water contact: showering/bathing - events/d, 1; event
duration 0.58 h (adult), 1.0 h (child); frequency 350
d/yr; exposure duration 30 yr (adult), 6 yr (child);
Swimming - site-specific.
Soil contact: events/d, 1; event duration 24 h (based on
experimental ABSd measurement time); frequency 350
d/yr (residential), 250 d/yr (industrial); exposure
duration 6 yr (child), 30 yr (adult residential), 25 yr
(adult industrial).
Under evaluation

Research studies include dermal methods development,
inclusion of dermal exposure in models under
development, e.g., SHEDS. Research study databases,
e.g., HEDS. Activity pattern studies and databases,
e.g., CHAD.


Skin areas
Exposed
skin areas
See Table 1











Under
evaluation
EFH
values, See
Table 1


Skin loading,
adherence
factor
Soil
adherence
factor, AF
(mg/cm2),
e.g., adult
residential
high-end
0.07; child
0.2; child
indoors 0.01




Not
applicable
Dermal
loading
(mg/cm2)



Dermal
absorption
Permeability
coefficients
Kp (cm/h) for
water; net
fraction
absorbed FA
for high-
molecular
weight
chemicals in
water; Soil
absorption
factors ABSd

Under
evaluation
Current
research areaa




Transfer
coefficients
Not used













Under
evaluation
Current
research areab



1 See for example, Griffin et al. (1999), Fenske and Elkner (1990).
3 See for example, Rodes et al. (2001).

-------
averaged between males and females to yield a single value, for example 18,150 cm2 in the
OPPTS ChemSTEER. OSRTI worker exposure is based on the assumption that head hands and
forearms are exposed such that the total exposed skin area is 3,600 cm2. Consumers are
subdivided as adults or children.  OPPTS uses an adult body weight of 71.8 kg except in PIRAT
which uses 70 kg. Both OSRTI and OW use an adult body weight of 70 kg. There is a wide
range of body weight assignments for children depending on the number of age group
subdivisions. Age grouping within divisions are different too such that infants are categorized as
0-2 years old (10.2 kg) in OPPTS EFAST but as children ranging in age from 1-6 years old (15
kg) in OSRTI. OPP has provisions for several age group ranges (infants, toddlers, and youth)
with corresponding levels of skin area exposed parameters.

3.1.2. Exposure Media
      Not surprisingly dermal exposure assessment interests in the Agency span a wide range
of media according to the mission and purview of each office.  Consequently it includes
exposure to industrial chemicals and intermediates during production, exposure associated with
the use of consumer products, including pesticides, and exposure to chemically contaminated
water, soil and sediment, and contact with chemically treated or contaminated surfaces.  Dermal
exposure from deposition of airborne chemicals can be estimated for certain industrial operations
using OPPTS ChemSTEER and for specific consumer product uses such as painting with OPPTS
EFAST and with OPP specific standard operating procedures such as spray applications
(Table 4). This does not apply to exposure to aerial  spray drift or to fumigation which are
evaluated with specific aerosol models. Dermal exposure via air is not considered by OSRTI.
Virtually all  of the offices address dermal exposure in chemically contaminated water, with
particular attention to swimming, showering and bathing (Table 5). Dermal exposure to soil is
explicitly addressed in OSRTI with methods to estimate soil adherence to skin and to estimate
dermal absorption.  It is not specifically addressed in OPPTS or OW.  Dermal exposure from
treated surfaces is addressed in OPPTS but not OW. OPPTS ChemSTEER and OPPTS EFAST
rely on defined exposure scenarios, OPP utilizes standard operating procedures.  In OPPTS the
focus is on worker exposures to industrial chemicals and intermediates and to consumer
exposures from liquids or solid consumer products used in water that are applied to hard surfaces
such as paints  and cleaners. In both cases several default scenarios are provided that can be
used to estimate exposure to the chemical of interest. In OPP the focus is  on commercial and
residential exposures associated with pesticide use.  The many standard operating procedures
address application of liquid or solid pesticide formulations as well as contact with treated
surfaces or impregnated materials.  OSRTI considers dermal exposure to both workers and the
public from chemically contaminated water and soil. Contamination may arise from  migration
of hazardous wastes in the environment due to run off or erosion and to infiltration of hazardous
waste chemicals into residences in proximity to hazardous waste sites.
                                          31

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     Table 4. Dermal exposure assessment methodology for chemical
     contaminants in air
EPA Office
OPPTS:
ChemSTEER
OPPTS: EFAST
OPP
OSWER:
Superfund
OW
ORD
Methodology
Scenarios include estimates of dermal exposures to airborne
contaminants deposited on skin from industrial operations, such as spray-
coating of automobiles.
Consumer product-related scenarios include estimates of dermal
exposures to airborne contaminants during application of products to
hard surfaces, such as painting.
Residential SOPs include spray applications of paints/stains and pet
pesticides. Spray drift and fumigant exposure are considered, based on
specific aerosol models.
Not covered.
Under evaluation. OW would also like to address dermal exposure via
vapors and aerosols.
Research methods, e.g., breath analysis to estimate dermal absorption. a
See, for example, Giardino et al. (1999), Corley et al. (1997).
     Table 5. Dermal exposure assessment methodology for chemical
     contaminants in water
EPA Office
OPPTS:
ChemSTEER
OPPTS:
EFAST
OPP
OSWER:
Superfund
OW
ORD
Comments
Pre-set scenarios for worker exposure during four industrial operations.
Includes exposure to additives from recirculating water-cooling towers. One-
hand liquid, two-hand liquid, and mass balance models.
Pre-set scenarios for consumer exposure include use of products that are added
to water. Site-specific general population exposure estimates for chemical
releases that enter surface waters. Models provide estimates of concentrations
and dermal dose rates.
Standard Operating Procedures include scenarios for swimming and
showering.
Methods for evaluating dermal-water exposure; for swimming and bathing,
entire skin surface assumed. Assumed significant only if dermal absorption is
likely to be >10% of the direct ingestion dose.
Under evaluation, with primary interest in general population dermal exposure
from water uses. Shower model under development.
Current research methods, e.g., methods to estimate dermal absorption from
water.a
See, for example, Gordon et al. (1998).
                                        32

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The OW is primarily interested in dermal exposure to chemically contaminated water associated
with uses such as swimming and bathing.

3.1.3.  Assumed and Default Parameters for Exposure Assessment
       Assumed and default characteristics vary widely across the Agency according to the
chemical and the nature of the exposure event under consideration. The orientation is largely for
chronic exposures though provisions are made for acute exposures. For example the averaging
time (AT)  for occupational exposure is 40 years for occupational exposure in OPPTS
ChemSTEER but ranges from 30 years to 75 years depending on the nature of the scenario and
product considered in OPPTS EFAST.  Skin area exposed may be based on general assumptions
such as one or two hands or on industry supplied data about the exposure event (see OPPTS
ChemSTEER and OPPTS EFAST).  Skin loading  may be estimated by use of a film thickness
estimate or by an adherence factor or by estimating dermal absorption. Dermal absorption can
be based on a percentage of the amount available on the skin or estimated by a permeability
coefficient. Transfer coefficients used to estimate the amount of a chemical residue that can be
dislodged from a treated surface and transferred to the skin range from 10,000 cm2/hr to 43,000
cm2/hr in adults depending on the exposure scenario.

3.2.    METHODOLOGY COMPARISON
       Comparative analysis among dermal exposure methodology is difficult because of the
focus on specific media in different program offices, unique attributes assigned to exposure
scenarios,  and assignment of upper percentile assumptions for parameters such as skin surface
area or exposure duration as discussed previously.  Moreover, the differences in these parameters
reflect user preferences to estimate exposure to the chemical of concern and situation
circumstances being evaluated.  Selection of the skin loading adherence factor, permeability
coefficient, Kp, and transfer coefficient represent key sources of variability among dermal
exposure methods.

3.2.1.  Skin Loading Adherence Factors
       Different approaches for skin loading adherence factors are recommended for dermal
exposure models.  In the OPPTS ChemSTEER model, the two-hand liquid loading on the skin
surface area S is set at 840 cm2, and the quantity Qu remaining on the skin is set at either 0.7 or
2.1 mg/cm2.  Similarly, for the two-hand solid  loading model or for direct contact with solids, the
quantity S times Qu is set at 3,100 mg/event. The model assumes that the quantity remaining on
the skin or surface loading per event is not affected by wiping off the  excess, nor do additional
contacts increase the quantity significantly. In the EFAST CEM a film-thickness approach is
used, which assumes a thin film of product on  a defined skin area. However, there are little
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supporting data on film thicknesses on skin and there are questions about the uniformity of such
films associated with product usage.
       To estimate dermal exposure from chemically contaminated soil, OSRTI employs a series
of default values for AF for a variety of exposure scenarios. For adult RME in residential
settings, the AF for a high-end soil contact activity such as gardening is 0.07 mg/cm2.
Residential average exposures for children while playing both in dry and wet soil uses a default
AF of 0.2 mg/cm2. For adult occupational exposures, the default AF is 0.2 mg/cm2.  Activity-
specific AF values are given for children and adults in several residential and commercial
settings, such as indoor and outdoor play, sports, construction work, and farming.

3.2.2.  Selection of a Permeability Coefficient
       All of these approaches permit the user to select a permeability coefficient, Kp, for the
chemical being evaluated. Measured Kp values can be found in the literature for many chemicals
or can be estimated by using the procedures in the Agency's Dermal Exposure Assessment:
Principles and Applications (DBA) guidance document (U.S. EPA, 1992a) or the RAGS E (U.S.
EPA, 2004a).  In the DEA guidance document Kp is provided for 90 chemicals and in RAGS E
the list has been updated to included more than 200 chemicals. In  RAGS E for chemicals not
listed, Kp can be estimated using a function of the octanol/water coefficient, Kow, and molecular
weight:

                        log KP = -2.80 + 0.66 log Kow  - 0.0056  MW                    (24)

where:
       Kp     =     Dermal permeability coefficient of compounds in water (cm/hr)
       Kow    =     Octanol/water partition coefficient of the non-ionized species
                    (dimensionless)
       MW    =     Molecular weight (g/mole).

       However, both measured Kp and estimated Kp are subject to substantial variability.
Measured Kp variability can be due to species of skin (human, rat,  swine), thickness of skin,
method of skin preparation, or the receptor fluid used in the method.  Estimated Kp is based on
the relationship of the Kow and the molecular weight of the compound of interest. However the
relationship does not hold well for small polar molecular weight compounds or for large
lipophilic compounds which make up most of the chemicals of interest to the Agency. The
degree of variability can be illustrated in the selection of the Kp for benzene for a dermal
exposure assessment in a Superfund investigation. In RAGS E, 0.015 cm/hr is the recommended
Kp but the California EPA recommends a Kp of 0.19 cm/hr based on the average of two studies
reported in the literature.
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3.2.3.  Selection of a Transfer Coefficient
       Various assumptions are used to estimate chemical transfer from treated or contaminated
surfaces to skin.  This is largely due to the lack of data concerning residue concentrations on
affected surfaces, how much can be removed by contact with skin, and the nature and extent of
activities where skin contact with affected surfaces occurs.  Transfer coefficients used in OPPT
PIRAT are 14,500 cm2/hr for adults and 5,200 cm2/hr for small children.  In the OPP SOPs, 20%
of an outdoor pesticide application is assumed to be transferable and 50% of an application
indoors to carpets or to hard floors.  The transfer coefficient default values for adults for outside
applications are typically 10,000 cm2/hr with a high end default of 43,000 cm2/hr 5,000 cm2/hr
for children age 10-12 and 8,700 cm2/hr for young children. For indoor applications transfer
coefficient default values are  16,700 cm2/hr for adults and 6,000 cm2/hr for children.

3.3.    DERMAL EXPOSURE ASSESSMENT METHODOLOGY FOR VARIOUS
       MEDIA
       The following tables, Tables 4-8, provide brief descriptions of the methods used by the
various U.S. EPA offices to estimate dermal exposures to chemicals in environmental and
occupational media.
       Table 6. Dermal exposure assessment methodology for chemical
       contaminates in soil
EPA Office
OPPTS:
ChemSTEER
OPPTS:
EFAST
OPP
OSWER:
Superfund
OW
ORD

Not covered.
Not covered.
Some chemical-specific studies have looked at hand-press transfer. Treated soil
may be assessed using specific study data or surrogate, depending on the
chemical and the method of exposure, e.g., potting, gardening, etc.
Methods for evaluating dermal-soil exposure included. Soil adherence factors
and dermal absorption values for 10 specific chemicals; screening estimates for
semivolatile organics. Assumed significant only if soil absorption >10% of
direct ingestion dose.
Not covered.
Current research methods, e.g., hand press, hand wipes, soil scrapings to obtain
concentrations (ng/g) and loadings (ng/m2). Development of transfer
coefficients and activity-related residential exposure data.
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     Table 7. Dermal exposure assessment methodology for treated surfaces
EPA Office
OPPTS:
ChemSTEER
OPPTS:
EFAST
OPP
OSWER:
Superfund
OW
ORD
Comments
Pre-set scenarios for worker contact during four industrial operations. A user-
defined option is available.
Pre-set scenarios for consumer contact with products applied to hard surfaces
Standard Operating Procedures for transfer from treated surfaces based on
dislodgeable residues, transfer coefficients, and dissipation rate. Post-
application from impregnated materials, such as painted surfaces, based on flux
rate of ai from material.
Methods for evaluating dermal-surface exposure included.
Not covered.
Research methods: Solid surface wipes to give concentrations (ng/g) and
loadings (ng/m2). Vacuum dust collections from carpeted surfaces.
Transferable (dislodgeable) residue collections though PUF roller and other
methods. a
See, for example, Wilson et al. (2004), Morgan et al. (2004).
     Table 8. Dermal exposure assessment methodology for occupational sources
EPA Office
OPPTS:
ChemSTEER
OPPTS:
EFAST
OPP
OSWER:
Superfund
OW
ORD
Comments
Pre-set scenarios for worker exposure during industrial operations: adhesives
formulation, new and refinishing spray-coating of automobiles, and
recirculating water-cooling towers. One-hand liquid, two-hand liquid, and mass
balance models require selection of a manufacturing operation and an activity.
Default parameters and user input.
Not covered.
Standard Operating Procedures for residential pesticide applications by
commercial applicators and by consumers. Exposure estimates from direct
contact during application and from contact with treated surfaces after
application. OPP's Antimicrobial Division has SOPs for industrial operations,
such as industrial mixing of paint.
Methods for evaluating dermal exposure to occupational sources included.
Default exposure values for dermal-water and dermal-soil pathways.
Not covered.
Not covered.
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    4.  DERMAL EXPOSURE ASSESSMENT TRENDS AND RESEARCH NEEDS

       The variety of methods, models, tools, and techniques described in this report underscore
the diversity of situations where the Agency considers dermal exposure in regulatory activities.
The complexity of the dermal pathway and the limited understanding of key aspects such as
dermal penetration and residue transfer efficiency necessitate continued efforts to better
characterize and assess dermal exposure in the Agency.  This section describes various research
needs to develop a more complete understanding about the dermal penetration process and an
improved characterization of exposure events where dermal contact occurs, especially for contact
with soil, sediment, and surfaces.  Though methods exist to estimate skin loading only a few
studies with soil and sediment have been conducted. Likewise methods have been described that
can estimate the amount of residue that can be transferred to skin from turf or surfaces but few
studies have been conducted to estimate the amount of transfer associated with actual activities.
More time location activity information would be useful to estimate the nature and extent of
activities where skin contact occurs from these sources for use in dermal exposure assessment
models and guidance documents.

4.1.    WATER
       The effective predicted domain used by Superfund for Kp estimates is based on the Flynn
database contained in DEA (U.S.  EPA, 1992a).  The Flynn database has not been expanded with
any new introduction of data from the literature though there are provisions to update the
RAGS E Appendix when new data are found in the scientific literature. A key issue pertains to
obtaining Kp for highly lipophilic compounds. Current in vitro dermal absorption methods are
suitable only for chemicals in aqueous solutions.  The solubility of highly lipophilic compounds
in these systems is limited to the point that the chemical is tied up in the skin layer and does not
penetrate through to a sufficient concentration to be measured. Yet many of the chemicals
addressed in Superfund site investigations are highly lipophilic compounds such as PCBs and
dioxins. In the absence of suitable Kp estimates for these compounds, Superfund managers must
perform uncertainty analyses as part of their assessments to account for the lack of quantitative
data for these compounds.
       To get into and through the skin, the chemical must dissolve into the stratum corneum,
which is a stabilized lipid barrier.  Hence lipid solubility is required initially, followed by water
solubility, to pass through the water-based gel portion of the skin and the human body, which is
water-based.  Unlike the water solubility data, no lipid solubility data have been collected, which
leaves a gap in the knowledge.  Because the Flynn database chemicals were not measured in the
same vehicle nor across the same  dose range and were studied with different procedures, the
results are difficult to compare. Research is needed to evaluate the Flynn database in
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conjunction with more recent reports of Kp in the literature to improve and expand the predicted
domain.

4.2.    SOIL
       In Superfund risk assessments, soil exposure is evaluated for residential and occupational
scenarios that incorporate exposure time and type of human contact with soil.  Skin soil loading
is determined using activity-specific surface area-weighted adherence factors as exposure factors
for soil. Empirical values are used for the specific fraction of chemicals absorbed to compensate
for the lack of data on soil matrix effects, such as contaminate aging on soils, soil carbon and
moisture content of soils, and percent absorbed and fraction absorbed from the soil matrix.
       Studies have shown that dermal loading depends on the type of activity, type of soil,
fineness of soil, soil moisture level, and moisture on the skin (which typically  increases transfer
to  skin).  Particle loading, mass balance and particle replacement rates are issues that are not
addressed well in existing Agency methods and models. Research is needed to better understand
the effects of soil composition such as carbon, clay, and moisture content and particle size on
skin loading and on dermal absorption of chemically contaminated soil.

4.3.    TREATED SURFACES
       Dermal exposure to treated surfaces is poorly characterized. Efforts are underway in
OPP and OSWER to better describe the parameters responsible for dermal exposure from these
sources.  In OPP, a transfer coefficient (TC) combined with the fraction of the amount of
material applied constitutes the basis for dermal exposure assessment from treated foliage and
surfaces. When application specific data are unavailable assumptions are used to estimate the
fraction of applied material available for transfer  (usually 5-10% depending on the treatment
site) and the amount transferred which is estimated from choreographed simulation studies
designed to represent the activities of interest. Efforts are underway to revise the SOPs that
guide these kinds of dermal exposure assessments.  Additionally, studies are being conducted to
determine the key features that influence TC such that more reasonable assumptions can be
incorporated into the SOP guidance.  OSWER is expanding dermal exposure assessments to
include contact with chemically contaminated surfaces. Both the Agency report: World Trade
Center (WTC) Indoor Environment Assessment:  Selecting Contaminants of Potential Concern
and Setting Health-Based Benchmarks (U.S. EPA, 2003b), and the OSWER guidance document
for PCBs under development address this issue.  The report incorporates transfer efficiencies
derived from the scientific literature to assess dry particle transfer to skin from hard surfaces.
The PCB draft guidance document contains information to calculate site-specific cancer and non-
cancer risks for dermal and ingestion pathways for PCB exposures. Appendix E of the document
addresses risks from PCB-contaminated solid surfaces using the protocol and method from the
WTC site investigation and some industrial site investigations in Region 3.  Default values have
                                          38

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been provided to develop screening levels for adults and children in a residential scenario and for
an indoor worker in an industrial scenario.  The guidance differs from the WTC approach by
including exposure form porous (e.g., wood, brick, concrete) and non-porous (stainless steel and
vinyl) surfaces. The approach used is a modification of the OPP approach.  Parameters for
application rates and residues are modified to reflect wipe samples, mass loading of dust,
children exposures over a 30-year period from age 1 to 31, and the introduction of a dissipation
factor to allow for removal of contaminants by cleaning.  More research is needed to evaluate the
generalizability of this guidance to other instances of exposure to contaminated surfaces.
       There is a general assumption in dermal exposure assessment methods and models that
clothing protects against exposure despite several studies that show this may not always be the
case depending on the chemical, its matrix, nature of the activity where exposure occurs, and the
type of clothing used for protection.  Research is needed to evaluate the studies that have been
conducted to characterize this issue and to conduct additional studies to determine the factors
where clothing may not be protective.
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                                 5.  CONCLUSIONS

       The Agency's interest in harmonization of dermal exposure assessment approaches is
based on the desire to generate transparent, reliable and reproducible risk assessments based on
sound science. Appropriate harmonization is a tool for making the best use of technical
resources, fostering consistency and a common basis for  selection of test methods and exposure
factors, and estimating dermal transport processes for dermal exposure assessment.  This report
shows that the kind of information that can be harmonized includes: databases of transport
parameters from different program offices, K estimates from the Agency's Superfund program,
transfer coefficients used by OPP for different pesticide application scenarios, and in vivo and in
vitro dermal absorption test methods used  by the Agency. Research is underway in many  of
these areas to generate data that could support harmonization efforts in the future.
       The OSWER Dermal Workgroup is evaluating the approach described in the World
Trade Center investigation and  the OPP standard operating procedures (SOPs) for residential
exposure assessments with other information to develop a protocol for dermal exposure to
contaminated surfaces as a new appendix in RAGS E (U.S. EPA 2004a, U.S. EPA, 2003b; U.S.
EPA, 1997a). The approach used is based on the procedures for contaminated soil to the extent
possible in an effort to estimate dermal absorption from contact with other types of surfaces,
such as floors, walls, furniture,  and vehicle seats which can then be used with the other parts of
RAGS E to address dermal risk from these surfaces. Additional research is needed to evaluate
the similarities and differences  of these approaches, to estimate contact with solids and to
determine the critical parameters for dermal exposure assessments
       In NERL, development  and application of quantitative structure-activity relationship
(predictive QSAR) models is underway to  produce the necessary parameters for data-intensive
PBPK models. Partition coefficients are used in PBPK/PD models to demonstrate the transfer of
materials through the skin, as well as between skin and blood. QSAR data (on absorption,
metabolic, tissue partitioning, enzyme inhibition and recovery parameters) can be tested in the
body of a PBPK model  to obtain information on where the chemical is in the body.  The vehicle
nature of the relationship of the skin to the stratum corneum and consequent absorption is  a
critical factor in assessing permeability especially when trying to compare in vivo and in vitro
results. Skin permeability models relying  on the Kow (or Log P) and molecular size (molecular
weight, V) are used as the main predictors. Steady state flux is measured in an in vitro system
using water and is used to derive the permeability coefficient Kp for chemical compounds. The
vehicle partition coefficient (Km/v) is a key part of the calculation and may be approximated by
the octanol-water partition coefficient (Kow).
       Challenges associated with these approaches include: the difficulty to assess lag time and
path length; that in vitro, aqueous systems  do not work for lipophilic compounds due to
solubility issues; molecular weight is not an adequate parameter (molecular volume, Bondi's
                                           40

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constants, and molar refractivity are better); 33% of the variation in the regression remains
unaccounted for; and a dichotomy exists between steady state in vitro and non-steady state in
vivo approaches. PBPK modeling uses provisional estimates to circumvent some of these issues
and to model  dermal chemical absorption based on a permeation coefficient. Studies of
chlorpyrophos, malathion and carbaryl are being conducted to improve the precision and
accuracy of this approach.
       NCEA is performing a critical review of the literature for soil models and evaluating their
ability to estimate dermal absorption.  This review is needed because of a lack of standard
protocols for  dermal exposure to chemically contaminated soil and a lack of data to validate
them. Based  on the results of the review, a protocol will be developed and a study of dermal
absorption to  chemically contaminated soil will be conducted to demonstrate the proper approach
to generate data for chemically contaminated soil. Additionally a parallel effort is underway to
investigate a dermal absorption model for chemicals in soil and sediment and to develop a
mechanistic model. This effort will address the fact that the current percent absorbed approach
falsely assumes that the same percentage applies under all exposure conditions.  The approach
will use in vitro experiments to explore absorption parameters and use the results to develop a
mechanistic model. Preliminary experimental results show that the monolayer (soil particle layer
immediately next to the skin) controls the flux and the layers above the monolayer contribute
very little to dermal absorption such that flux does not increase as concentration exceeds the soil
saturation level.
       The results of the many activities and investigations summarized in this report serve as a
reference document for Agency risk assessors who deal with assessing the consequences of
dermal exposure to chemical contaminants in the environment. It is intended to foster discussion
about information sharing and harmonization and to support additional research to improve
dermal risk assessment methodology in the Agency.
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                                    REFERENCES


ATSDR (Agency for Toxic Substances and Disease Registry). (2007) Toxicological profiles.
U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease
Registry, Atlanta, GA. Available online at http://www.atsdr.cdc.gov/toxfaq.html.

Bunge, AL; McDougal, NJ. (1999). Dermal uptake. In: Olin, SS, ed. Exposure to contaminants
in drinking water. Estimating uptake through the skin and by inhalation. Boca Raton, FL: CRC
Press; pp. 137-181.

Corley, RA; Markham, DA; Banks, C; et al. (1997) Physiologically based pharmacokinetics and
the dermal absorption of 2-Butoxy-ethanol vapor by humans. Toxicol Sci 39(2): 120-130.

Fenske, RA; Elkner, KP. (1990) Multi-route exposure assessment and biological monitoring of
urban pesticide applicators during structural control treatments with chlorpyrifos. Toxicol Ind
Health 6:349-371.

Franz, TJ. (1975) Percutaneous absorption: on the relevance of in vitro  data. J Invest Dermatol
64:190-195.

Geer, LA; Cardello, N; Dellarco, M; et al. (2004) Comparative analysis of passive  dosimetry and
biomonitoring for assessing chlorpyrifos exposure in pesticide workers. Ann Occup Hyg
48(8):683-695.

Giardino, NJ; Gordon, SM; Brinkman, MC;  et al. (1999) Real-time breath analysis of vapor
phase uptake of 1,1,1-trichloroethane though the forearm: Implications  for daily  absorbed dose
of volatile organic compounds at work. Appl Occup Environ Hyg 14(11):719-727.

Gordon, SM; Wallace, LA; Callahan, PJ; et al. (1998) Effect of water temperature on dermal
exposure to chloroform. Environ Health Perspect 106(6):337-345.

Griffin, P; Mason, H; Heywood, K; et al. (1999) Oral and dermal absorption of chlorpyrifos:  a
human volunteer study. Occup Environ Med 56:10-13.

Jackson, JR. (1999) Issues relating to the risk assessment of dermal exposures. An  output of the
EU Dermal Exposure Network.  Report, University of Surrey, United Kingdom.  December.

Kissel, JC; Richter, KY; Fenske, RA. (1996) Field measurements of dermal soil loading
attributable to various activities: Implications for exposure assessment.  Risk Anal 16(1): 115-125.

McCurdy, T; Glen, G; Smith, L; Lakkadi, Y. (2000) The national  exposure research laboratory's
consolidated human activity database. J Expo Anal Environ Epidemiol  10(6):566-578.

Morgan, MK; Sheldon, LS; Croghan, CW; et al. (2004) Exposures of preschool children to
chlorpyrifos and its degradation product 3,4,5-trichloro-2-pyridinol in their everyday
environments. J Expo Anal Environ Epidemiol 15(4):297-309.
                                          42

-------
NIOSH (National Institute for Occupational Safety and Health). (1997) Registry of toxic effects
of chemical substances (RTECS). U.S. Department of Health and Human Services, Centers for
Disease Control and Prevention, Cincinnati, OH. DHHS (NIOSH) Publication No. 97-119.
Available online at http://www.cdc.gov/niosh/pdfs/97-n9.pdf

OECD (Organization for Economic Co-Operation and Development). (2004) Test No.  428: Skin
absorption: in vitro method.  In: OECD Guidelines for the testing of chemicals, Section 4:
Health Effects. OECD Publishing, Paris; pp 1-8. Available online at
http://213.253.134.43/oecd/pdfs/browseit/9742801E.PDF.

PHED (Pesticide Handler Exposure Database). (2007) Pesticide Handler Exposure Database.
Database created for U.S. Environmental Protection Agency and Health Canada.  Available from
Versar, Inc., Port Orange FL. Available at http://members.aol.com/dsdprogram/phed.htm.

Roberts, MS; Walters, KA. (1998) The relationship between structure and barrier function of the
skin. In: Roberts, MS. Walters, KA, eds. Dermal absorption and toxicity assessment. New York,
NY: Marcel Dekker; pp 1-42.

Rodes, C; Newsome, R; Vanderpool, R; et al. (2001) Experimental methodologies and
preliminary transfer factor data for estimation of dermal exposure to particles. J Expo Anal
Environ Epidemiol 11(2):123-139.

Sartorelli, P; Andersen, HR;  Angerer, J; et al. (2000) Percutaneous penetration studies for risk
assessment. Environ Toxicol Pharmacol 8:133-152.

TOXNET. (2007) Toxicology data network. United States National Library of Medicine,
National Institutes of Health, Bethesda, MD. Available  online at http://toxnet.nlm.nih.gov/.

U.S. EPA (Environmental Protection Agency). (1992a) Dermal exposure assessment: Principles
and applications, Interim Report. Exposure Assessment Group, Office of Health and
Environmental Assessment,  U.S. Environmental Protection Agency, Washington DC;
EPA/600/8-91/01-01 IB.

U.S. EPA (Environmental Protection Agency). (1992b) Guidelines for exposure assessment.
Risk Assessment Forum, U.S. Environmental Protection Agency, Washington DC;
EPA/600/Z-92/001. Available online at
http://cfpub.epa.gov/ncea/raf/recordisplay.cfm?deid= 15263.

U.S. EPA (Environmental Protection Agency). (1992c) Methods for assessing exposure to
chemical substances,  Volume 11. Methodology for estimating the migration of additives and
impurities from polymeric materials. Office of Pesticides and Toxic Substances, U.S.
Environmental Protection Agency, Washington, DC; EPA/560/5-85-015.

U.S. EPA (Environmental Protection Agency). (1995) DERMAL exposure model description
and user's manual, draft report.  Prepared for the U.S. Environmental Protection Agency, Office
of Pollution Prevention and Toxics by  Versar, Inc. Under contract No. 68-D3-0013.

U.S. EPA (Environmental Protection Agency). (1997a) Standard operating procedures (SOPs)
for residential exposure assessments. Office of Prevention, Pesticides, and Toxic Substances,
U.S. Environmental Protection Agency, Washington, DC. Available online at
http://www.epa.gov/scipoly/sap/meetings/1997/september/sopindex.htm.
                                          43

-------
U.S. EPA (Environmental Protection Agency). (1997b) Exposure factors handbook. National
Center for Exposure Assessment, Office of Research and Development, U.S. Environmental
Protection Agency, Washington DC; EPA/600/P-95/002Fa. August 1997. Available online at
http://www.epa.gov/ncea/pdfs/efh/front.pdf.

U.S. EPA (Environmental Protection Agency). (1999) OP case study group, non-dietary
subcommittee, REx residential exposure assessment, generic methods case study: Lawn care
products December 15, 1999. Office of Prevention, Pesticides and Toxic Substances, U.S.
Environmental Protection Agency, Washington, DC. Available online at
http://www.epa.gov/scipoly/sap/meetings/2000/september/rex_turf_case_study.pdf

U.S. EPA (Environmental Protection Agency). (2000a) Summary report for the workshop on
issues associated with dermal exposure and uptake. Risk Assessment Forum, U.S. Environmental
Protection Agency, Washington DC; EPA/630/R-00/003. Available online at
http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=20679.

U.S. EPA (Environmental Protection Agency). (2000b) Characterization and non-target
organism data requirements for Protein Plant-pesticides. Presented at the FIFRA Scientific
Advisory Panel Meeting, December 8-9, 1999, held at the Sheraton Crystal City Hotel and Days
Inn, Crystal City Hotel, Arlington, VA. Sponsored by FIFRA Scientific Advisory Panel, U. S.
Environmental Protection Agency.  SAP Report No. 99-06.

U.S. EPA (Environmental Protection Agency). (2000c) Cumulative risk assessment methodology
issues of pesticide substances that have a common mechanism of toxicity. Presented at the
FIFRA Scientific Advisory Panel Meeting, December 8-9, 1999, held at the Sheraton Crystal
City Hotel and Days Inn, Crystal City Hotel, Arlington, VA. Sponsored by FIFRA Scientific
Advisory Panel, U. S. Environmental Protection Agency. SAP Report No. 99-06.

U.S. EPA (Environmental Protection Agency). (2003a) Example exposure scenarios. Chapter 4:
Example dermal exposure scenarios. National Center for Environmental Assessment, U.S.
Environmental Protection Agency, Washington DC; EPA/600/R-03/036. Accessed April 2004 at
http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=85843.

U.S. EPA (Environmental Protection Agency). (2003b) World Trade Center (WTC) indoor
environment assessment: Selecting contaminants of potential concern and setting health-based
benchmarks, May 2003. Prepared by the Contaminants of Potential Concern (COPC) Committee
of the World Trade Center Indoor Air Task Force Working Group.  Available online at
http ://www. epa. gov/wtc/copc  study .htm.

U.S. EPA (Environmental Protection Agency). (2004a) Risk assessment guidance for Superfund
(RAGS), Vol I: Human health evaluation manual, Part E, supplemental  guidance for dermal risk
assessment, Final. Office of Solid Waste and Emergency Management,  Office of Superfund
Remediation and Technology Innovation, U.S. Environmental Protection Agency, Washington
DC. Available online at http://www.epa.gov/superfund/programs/risk/ragse/index.htm.

U.S. EPA (Environmental Protection Agency). (2004b) ChemSTEER B Chemical screening tool
for exposures and environmental releases.  Office of Prevention, Pesticides and Toxic Substances,
U.S. Environmental Protection Agency, Washington, DC. Available online at
http://www.epa.gov/opptintr/exposure/pubs/chemsteerdl.htm.
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U.S. EPA (Environmental Protection Agency). (2004c) 2004 research abstracts. National
Exposure Research Laboratory, U.S. Environmental Protection Agency, Washington, DC.
Available online at http://www.epa.gov/nerl/research/2004/resh2004.html.

U.S. EPA (Environmental Protection Agency). (2004d) Exposure research models. National
Exposure Research Laboratory, U.S. Environmental Protection Agency, Washington, DC.
Available online at http://www.epa.gov/nerl/topics/models.html.

U.S. EPA (Environmental Protection Agency). (2004e) Estimated per capita water ingestion and
body weight in the United States-An update based on data collected by the United States
Department of Agriculture's 1994-1996 and 1998, continuing survey of food intakes by
individuals. Office of Water, Office of Science and Technology, U.S. Environmental Protection
Agency, Washington, DC; EPA/822/R-00/001. Available online at
http://www.epa.gov/waterscience/criteria/drinking/percapita/2004.pdf

U.S. EPA (Environmental Protection Agency). (2005) Summary report of the colloquium on
dermal exposure methods comparison April 12, 2005. Final Report June 9, 2005. Available
online at http://cfmt.rtpnc.epa.gov/ncea/raf/recordisplay.cfm?deid=135421.

U.S. EPA (Environmental Protection Agency). (2007a) EFAST B Exposure, fate  assessment
screening tool. Office of Prevention, Pesticides and Toxic Substances, U.S. Environmental
Protection Agency, Washington, DC. Available online at
http://www.epa.gov/opptintr/exposure/pub s/efast2man. pdf.

U.S. EPA (Environmental Protection Agency). (2007b) Integrated risk information system
(IRIS). National Center for Environmental Assessment, Office of Research and Development,
U.S. Environmental Protection Agency, Washington, DC. Available online at
http://www.epa.gov/iri s/.

U.S. EPA (Environmental Protection Agency). (2007c) Minutes of the January 9-12, 2007
Federal Insecticide, Fungicide, and Rodenticide Act scientific advisory panel meeting. Available
online at http://www.epa.gov/scipolv/sap/meetings/index.htmtfjanuary.

U.S. EPA (Environmental Protection Agency). (2007d) Pesticide inert risk assessment tool
(PIRAT). Office of Prevention, Pesticides and Toxic Substances, U.S. Environmental Protection
Agency, Washington, DC. Available online at
http://www.epa.gov/opptintr/exposure/pub s/pirat.htm.

U.S. EPA (Environmental Protection Agency). (2007e) Human exposure database system
(HEDS). Office of Research and Development, U.S. Environmental Protection Agency,
Washington, DC. Available online at http://www.epa.gov/heds/aboutheds.htm.

Versar. (1992) A laboratory method to determine the retention of liquids on the surface of hands.
Report to USEPA/OPPT, Contract 68-02-4254.

Wester, RC; Maibach, HI. (1999) In vivo methods for percutaneous absorption measurements.
In: Bronaugh, RL; Maibach, HI; eds. Percutaneous absorption: Drugs - cosmetics - mechanisms
- methodology, 3rd edition, Revised and Expanded. New York, NY: Marcel Dekker, Inc.;
pp. 215-228.
                                          45

-------
Wilson, NK; Chuang, JC; lachan, R; et al. (2004) Design and sampling methodology for a large
study of preschool children=s aggregate exposures to persistent organic pollutants in their
everyday environments. J Expo Anal Environ Epidemiol 14:260-274.

Zartarian, V. (2003) Assessing children's exposures to pesticides: An important application of
the Stochastic Human Exposure and Dose Simulation Model (SHEDS). Available online at
http://www.epa.gov/ord/scienceforum/PDFs/science/zartarian  v.pdf (Last modified 4/21/2003).

Zendzian, RP. (1994) Pesticide assessment guidelines. Subdivision F: Hazard evaluation,
humans and domestic animals. Series 85-3. U.S. Environmental Protection Agency, Washington,
DC.

Zendzian, RP. (2000) Use of in vitro dermal penetration studies to compare rat and human
penetration of chemicals. Presented at the Annual Meeting of the Society for Risk Analysis,
Arlington, VA, December 3-6, 2000. Available online at
http://www.riskworld.com/Abstract/2000/SRAamOO/abOac403.htm.

Zendzian, RP; Dellarco, M. (2003) Validating in vitro dermal absorption studies,  an introductory
case study.  In: Salem, H; ed. Alternative toxicological methods for the new millennium. Boca
Raton, FL:  CRC Press; pp. 205-217.
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