APPENDIX A

Micro- Versus Macro-Event Dermal Exposure Estimation Methods

Introduction

Human exposures to agents - biological, chemical, physical and radiological - can occur through the ingestion, inhalation and dermal routes. The relative significance of the dermal route has been recognized in various occupational settings (e.g., agricultural worker reentry into pesticide treated crops), and more recently in the residential environmental (Popendorf 1976, Popendorf, 1985; Fenske, 1990; Ross et al., 1990 and 1991; Harris and Solomon, 1992; Harris et al., 1992; Lewis et al., 1994; Driver and Whitmyre, 1997). A variety of direct (skin surface sampling) and indirect (environmental surface sampling, videography) measurements of dermal exposure have been developed including: surrogate skin surface methods: cotton dosimeter patches and garments (Durham and Wolfe, 1962; Ross et al., 1990); removal methods: hand rinses or wipes (Davis et al., 1983; Lewis et al., 1994; Fenske and Lu, 1994); videotaping of human volunteers and analysis dermal exposure-related variables (Zartarian et al., 1995; Zartarian and Leckie, 1997; Zartarian and Leckie, 1998); video imaging of skin surfaces exposed to fluorescent tracer compounds (Archibald et al., 1994 and 1995; Black and Fenske, 1996) and surface sampling methods: surface extraction, surface wipes, vacuum methods for dust, drag sleds, rollers and hand press (Popendorf 1985; Zweig et al., 1985; USEPA, 1990; Roberts et al., 1992; Lioy et al., 1993; Lewis et al., 1994; Black and Fenske, 1996; Ross et al., 1991; Vaccaro et al., 1996). However, the study designs that utilize these methods of dermal exposure measurement do not consistently characterize spatial and temporal variability and other key processes necessary to develop and validate realistic physical-stochastic predictive models.

Dermal exposure (and subsequent absorption kinetics) represents a dynamic, complex process with multiple, potential rate-limiting phenomenon and highly variable factors (Ott 1985; McKone 1991; USEPA, 1992 and 1996; Matoba 1996; Zartarian and Leckie, 1998; Hubal et al. 1999). In environments such as the residence, this complexity can be attributed, in part, to time-dependent dislodgeability and transferability for different surface types (e.g., foliage, carpet, hardwood floors), spatial variability in surface concentration, environmental conditions (e.g., temperature, humidity), and related differential dermal “body part” surface area loading and removal rates as a function of human time-activity patterns and biomechanical variables (e.g., frequency and duration of body part surface area contacted and the associated pressure exerted on the area of environmental surface contacted). Dermal exposure assessment to subpopulations, such as infants and children, must also address secondary pathways, such as incidental ingestion associated with hand-to-mouth behavior. Further, the relative bioavailability of a given agent from various exposure media is often uncertain (Driver et al., 1989).

The development of more realistic models of dermal exposure is being facilitated by a variety of research programs initiated in part, due to the requirements of the Food Quality Protection Act of 1996. This amendment to the Federal Insecticide, Fungicide and Rodenticide Act establishes a single, consistent, health-based standard for pesticide residues in food, emphasizes child safety and formalizes the EPA’s strategic approach to better understanding non-occupational exposures in the residential environment, including those via the dermal route. Research programs include the EPA-funded National Human Exposure Assessment Survey and by industry-sponsored exposure data development activities, such as the Outdoor Residential Exposure Task Force and the Non-Dietary Exposure Task Force, both formed, in part, to respond

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to the EPA’s recent call for improved estimates of residential exposure. The following paper provides an historical perspective of the dermal exposure assessment with particular reference to the agricultural worker reentry and residential settings, followed by presentation of two alternative approaches to physical-stochastic modeling (i.e., macro-and micro-based) that can be implemented and validated, in part, based on the data development initiatives noted above. Historical Perspective: Review of Exemplary Dermal Modeling Approaches

Modeling Agricultural Reentry Dermal Exposures

Exposures of harvesters to pesticide residues on crops and their foliage has been the subject of research for over 50 years (Abrams and Leonard, 1950). A significant component of these investigations has been evaluating and measuring dermal exposure variables that are associated with various crop reentry/work activities (Popendorf 1985). These include spatial variability in foliar deposition due to spray drift, foliar versus ground deposition, dissipation due to evaporation, degradation mechanisms, rainfall, foliar absorption, adsorption/desorption processes (e.g., dislodgeable foliar residues), reentry into initial versus repeat treatment areas, crop-fruit geometry and size/stage of crop growth, foliage-picker orientation, specific worker practices/activities and their duration, worker clothing configurations, physiology and personal hygiene (Krieger et al., 1990; Popendorf, 1985).

As noted above, one of the key variables associated with estimation of reentry dermal exposures is dislodgeable foliar residue (DFR) which is the amount of residue on plant foliage that can be dislodged using aqueous extraction methods. DFR represents the amount of residue that is potentially available as a source of dermal exposure for workers harvesting, weeding or working in previously treated fields. The design of the study will indicate when leaf samples are to be obtained, but samples are generally taken at 4 to 12 hours and at 1, 2, 5, 7, 14, 21, 28 and 35 days post-application. A leaf punch is used to sample 400 cm2 of foliage from the top, medium and lower strata of the plant canopy. Exemplary foliar dislodgeable residue data are provided in Table A-1.

TABLE A-1. Hypothetical DFR-related data. CROP Application

Rate (lbs/acre)

Spray Volume (gallons/acre)

Initial DFR (ug/cm2)

DFR Half-life (days)

Percent Dissipated (per day)

STUDY DESIGN

Broccoli 1.1 33 0.9 5.0 13 Eight applications; sampled at 0, 1, 2, 5, 8, 15, 22, 29 and 30 days

Cucumber 2.3 33 4.5 3.5 18 Five applications; sampled at 0, 1, 2, 5, 8, 15, 22, 30 and 37 days

Cherry 3.1 102 1.4 3.5 18 Four applications; sampled at 0, 1, 2, 5, 8, 15, 22, 29, 36 and 43 days

DFR data are used in conjunction with worker dermal monitoring data (e.g., cotton dosimeter garments or body-part-specific “patches”) to derive transfer coefficients (TCs, expressed in units of cm2/hr) which can then be used to estimate the amount of pesticide that is transferred from a previously treated surface onto workers. TCs are different from DFRs in that they are believed to not be pesticide-specific, but are more dependent on other variables such as the crop treated, the nature of the job and the extent of foliar contact. Thus, “generic” transfer coefficients can be developed by applying a pesticide to a specific crop and determining dermal exposure as a function of DFR and time.

A general dermal exposure modeling approach that incorporates some of the factors described above has been presented as follows (Popendorf, 1985): Dermal Exposure (µg; mass deposited on harvester’s skin) = (kd)(t)Ro

(-kr)(T) Where, kd = cm2/hr; crop/activity-specific residue transfer coefficient - crop

foliage surface area contacted per unit time t = hrs; work exposure period Ro = mg/cm2; initial dislodgeable foliar residue - mass per unit surface

area of treated crop foliage kr = unitless; pesticide-specific dislodgeable foliar residue decay

coefficient T = days; reentry interval

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Crop/activity-specific values for kd have been estimated by various investigators based on body-part-specific dermal dosimetry data as follows: kd = Dermal Exposure / (t) (R) Where, Dermal Exposure = mass deposited on harvester’s skin (µg; dermal loading for

total body or for specific body) t = hrs; work exposure period R = µg/cm2; time-specific residue mass per unit surface area of

treated crop foliage

The Agricultural Reentry Task Force (ARTF), an agricultural industry coalition, is sponsoring a series of reentry studies to further characterize the above dermal loading equation proposed by Popendorf and to develop kd values for various crops and activities. Exemplary transfer coefficient values reported by Popendorf (1985), and recommended by the U.S. EPA and CA DPR are provided in Tables A-2, A-3 and A-4. [to be modified based on additional data/info from the USEPA and CA EPA; add 3-D plot of DFR, dermal dosimetry data and time?] TABLE A-2. Summary of harvester kd transfer coefficient values (cm2/hr) based on projected or total foliar surface area (adapted from Popendorf, 1985).

CROP kd based on one-sided foliar surface area

kd based on two-sided foliar surface area

Citrus 5,000a 10,000

a

Peaches 1,900b

3,800b

Grapes 1,600 3,200

Strawberries 4,000c 8,000

c

Tomatoes

(mechanical) 33d 67d

a) dose adjusted for knit glove penetration

b) value extrapolated from foliar versus airborne dust correlations (Popendorf et al., 1982, as cited in Popendorf 1985)

c) dose not adjusted for wet glove effect (Zweig et al., 1985; Noel et al., 1983, as cited in Popendorf 1985)

d) dose to operators normally wearing vinyl-rubber gloves

TABLE A-3. Examples of “generic” transfer coefficients for various work task/body contact/crop combinations. WORK TASK BODY

CONTACT AREAS

CROP TRANFER COEFFICIENT (TC; cm2/hr)

Sort/select Hand Tomatoes (mechanical) 100 Reach/pick Hand + arm Lettuce 200 – 700 Reach/pick Hand + arm + leg Tomatoes (pole) 1,000 – 3,000 Search/reach/pick Upper body Tree fruit 3,000 – 6,000 Expose/search/reach/pick Whole body Grapes 8,000 – 25,000

TABLE A-4. Exemplary transfer coefficients based on field studies conducted in California, 1987-1989, using a variety of monitoring techniques [standard work clothing typical included shoes, socks, long pants and long-sleeved shirts, except: a) gloves; b) new nylon pickers gloves; c) used nylon pickers gloves; d) rubber latex gloves worn by all workers; transfer factors were calculated by dividing potential dermal exposure (PDE; external) by the product of time (8 hrs) and dislodgeable foliar residue (DFR; :g/cm2)] (adapted from Krieger et al., 1990). CROP Work

Task Chemical DFR

(:g/cm2) PDE (mg/day)

DDE (mg/day)

Transfer Coefficients (cm2/hr) Standard Plus Gloves

Tomato Pole Chlorothalonil 1.9 324 32 21,000 1.9 189 19 12,000b 1.9 255 25 17,000c 1.9 105 11 7,000d Bush-hand Chlorothalonil 3.1 229 23 9,000 Bush-mechanical

Chlorothalonil 0.7 7 1 1,000

Lettuce Cutter Folpet 0.6 64 6 13,000d Packer Folpet 0.6 31 3a 6,000d Strawberry Harvester Captan 1.77 85 5 6,000d Malathion 0.24 1 0.1 500d Dicofol 1.44 24 1.5 2,000d Naled 0.59 6 0.4 1,000d Peach Harvester Azinphosmethyl 0.27 116 9 54,000 Phosmet 2.5 485 39 24,000 Nectarine Harvester Azinphosmethyl 0.31 17 7,000 Plum Thinning Phosmet 0.02 63 6 390,00

0

Apple Harvester Azinphosmethyl 0.63 29 2 6,000 Grape Cane-

cutting Captan 0.5 66 7 17,000

Harvester Captan 0.3 43 4 18,000

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( ) ( )

Modeling Residential Reentry Dermal Exposures

Indoor and outdoor use of pesticide chemicals present opportunities for dermal exposure. The FQPA requires the EPA to estimate potential multipathway, multiroute exposure (dermal, inhalation, incidental ingestion) during and following use of pesticide products in and around the home. Further, potential residential exposures to children continues to receive emphasis in discussions surrounding federal legislative and regulatory initiatives, including FQPA. Dermal exposure of children in the residential environment, following the use of a consumer or professional pesticide product, may occur through contact with different surfaces (e.g., carpets, rugs, hardwood floors, turf, treated pets). Residential exposure modeling, including the dermal route, involves a variety of influential factors as illustrated in Figure 1. Approaches to post-application dermal exposure modeling in the residential environment (indoor and outdoor), have relied on the use of environmental surface and dermal dosimetry measurements in conjunction with assumptions regarding “representative” or “worst-case” time-activity patterns for subpopulations of interest (USEPA, 1999a; USEAP1999b; ILSI, 1998; Ross et al., 1990 and 1991; Vaccaro et al., 1996).

A more recent “macro-event” based approach to post-application dermal exposure modeling involves the use of body part-specific “transfer factor” (TF) point estimates and/or underlying distributions. The unitless TFs represent an activity-specific basis for estimating dermal loading :g/cm2 for various anatomical regions from compound-specific transferable residue data (:g/cm2). The general equation for estimating potential body-part-specific dermal exposure can be described as follows: Post-Application Dermal ExposureBody Part (:g) =

(

)[ ]= ∑ Trans Factor x Transferable sidue x Surface AreaBodyPart BodyPartRe

Where, Transfer Factor (TF) = unitless; “generic” body-part-specific factor relating transferable residue values to “Jazzercise™ equivalent” dermal exposure

Transferable residue = :g/cm2; chemical-specific; mass of residue per unit

surface area transferring from a treated surface to a “surrogate skin” collection medium (e.g., cotton dosimeter)

Surface area = cm2; skin surface area represented by a specific

body part

The transfer factor-based dermal modeling approach can be illustrated for estimating potential post-application dermal contact with floor surfaces on which aerosols have deposited by using the Jazzercise™ study conducted by Ross et al. (1990 and 1991). This study provides a means for conservatively estimating potential post-application dermal exposures to treated surfaces following the use of indoor total release foggers by using a high-contact, but reproducible activity. The procedure for estimating potential dermal exposure is based on the use of “transfer factors” or TFs derived from the human volunteer dermal dosimetry and treated carpet “transferable residue” measurements based on an indoor roller method (Ross et al., 1990 and 1991). The Ross et al. (1990) study measured the transfer of pesticide residues (chlorpyrifos and d-trans allethrin) from carpeted floor to five human subjects wearing dosimeter clothing following the use of home-fogger devices. Subject motions were standardized using a 20-minute (18.2 minute routine plus entry and exit time) aerobic dance routines (Jazzercise™). This method provided reproducible dosimeter exposure measurements and derivation of transferable residue estimates - transfer of surface residues to exposed subjects. The study was conducted in recently constructed hotel rooms in Sacramento, CA. Two hours after fogger treatment, the rooms were vented for 30 minutes by opening windows. Sampling methods included aluminum fallout sheets (400 cm2) and cotton dosimeter clothing (socks, gloves, pants and shirts). The Ross et al. (1991) study demonstrated use of a standardized, reproducible method for measuring transferable residues to supplement the study conducted by Ross et al. (1990). The monitoring device (the CDFA or CDPR roller) was a cylinder that was rolled over a cotton cloth that was placed on the treated surface (i.e., carpet). The method was shown to transfer 1 to 3 percent of potentially available pesticide material from nylon carpeting to the collection media (cotton cloth). Transfer from carpet to cloth was found to be highly correlated with transfer to cotton clothing worn by persons exercising on the carpet (Ross et al., 1990). It is important to note that transfer factor-based modeling inherently considers only the activities and time domain included in the dermal monitoring study from which the factors are derived. Therefore, if the study design, such as the case with Jazzercise™, represents a high-contact activity, it must be placed in perspective with more representative time-activity profiles (USEPA, 1996; ILSI, 1998). For example dermal exposures associated with 20 minutes of Jazzercise™ (whether on indoor or outdoor surfaces) may be similar to or greater than an entire day of exposure (non-sleeping period) associated with more representative activities (e.g., sitting, walking, playing on floor surfaces) on the same surfaces (and with all other product use and environmental conditions being equivalent) (ILSI, 1998). The following section presents a practical, integrated physical-stochastic dermal model that represents a synthesis of the above described approaches (transfer coefficient- and transfer factor-based) and provides for incorporation of other key deterministic variables. Macro-Based Dermal Exposure Methodology

The following four elements are presented as part of the integrated dermal exposure assessment methodology/model:

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1) Multiple environmental surfaces, multiple dermal surfaces, dermal contact 2) Single environmental surface, single dermal surface, dermal contact 3) Hand-to-mouth contact 4) Time-dependent dermal contact Scenario 1 Exposure medium: Environmental surfaces Environmental surfaces: Multiple Exposure route: Dermal contact Dermal surfaces: Multiple Inputs Menv mass of chemical applied to environmental surfaces (:g) Fenv fraction of chemical depositing on environmental surfaces Aenv area of environmental surfaces treated (cm2) J number of zones in environmental surfaces Fchem, j fraction of chemical applied to environmental surface zone j Farea, j fraction of area in environmental surface zone j Fdis, j fraction of chemical dislodgeable from environmental surface zone j Ader area of dermal surfaces affected (cm2) K number of regions in dermal surfaces Farea, k fraction of area in dermal surface region k Ftrans, j→k, fraction of chemical transferred from zone j (environmental surface) to region k

(dermal surface) per contact Fmod, (j,k) exponential factor that modifies Ftrans, i→k based on the contact number Ncon, (j,k) number of region k (dermal surface) contacts with zone j (environmental

surface) per hour (#/hr) Texp exposure duration (hr)

In Scenario 1, a certain amount of chemical (mass = Menv) is applied to multiple environmental surfaces. In indoor environments, surfaces could include carpet, vinyl, wood, tile, drywall, wallpaper, particle board, marble, and granite covered floor, wall and counter-top surfaces; furniture coverings; and object surfaces (e.g., toys, plants, appliances, etc.). In outdoor environments, surfaces could include grass, plant, soil, fence, and concrete coverings; furniture coverings; and object surfaces (e.g., toys, trampoline, etc.). A fraction of the chemical that is applied does not deposit on the surfaces. It can disperse in the air medium and be transported through air flow away from the room and/or deposit on the application equipment, including the applicator. The fraction that deposits on the environmental surfaces is denoted by Fenv.

In a residential setting, multiple environmental surfaces can be explained by two different situations. In one situation, a chemical can be broadcast homogeneously in a living room that has partly carpeted and partly wood-covered floor. In this case, there are two environmental

surfaces (J = 2); namely, carpeted and wood-covered floor. In the other situation, when a chemical is sprayed in a carpeted in a room along the edges formed by the floor and the side walls, three homogeneous environmental zones (J = 3) can be assumed to be created. The first assumed homogeneous surface is the carpeted floor area close to the edge, the second is the carpeted floor area away from the edge and close to the center of the room, and the third is the side wall area close to the edge.

The homogeneously different environmental surfaces are designated as zones: zone j, j = 1, 2, …, J. The total area of all the environmental surfaces is denoted as Aenv. Farea, j and Fchem, j refer to zone j area as a fraction of Aenv and to chemical depositing on zone j as a fraction of Menv respectively.

When a chemical deposits on an environmental surface, only a certain fraction can be physically dislodged from the surface. The characteristics of both the chemical and the surface dictate that not all the chemical that deposited on the surface can be dislodged. The fraction that can be dislodged from environmental surface zone j is denoted as Fdis, j. For a given environmental surface, Fdis, j can be estimated by using a form of solvent-extraction, multiple drag, or multiple roller studies.

Similar to the concept of multiple environmental surfaces, the dermal surfaces contacting the different environmental surfaces can be divided into multiple surfaces. The homogeneously different dermal surfaces are designated as regions: region k, k = 1, 2, ….., K. The total area of all the dermal surfaces is denoted as Ader.

For a single contact of a dermal surface region with an environmental surface zone, the fraction of chemical transferred from the latter to the former is set to Ftrans, j→k. Ftrans, j→k is a function of the characteristics of the chemical, the environmental surface, and the dermal surface. Also, with increasing contact number, Ftrans, j→k decreases; in other words, (Ftrans, j→k for contact number 1) > (Ftrans, j→k for contact number 2) > ….. > (Ftrans, j→k for contact number N). To account for this decreasing Ftrans, j→k, a modifier is used. This modifier is represented as an

exponential function: ( )( )eF nj k− ×mod,( , ) 1−

, where Fmod, (j,k) is the exponential factor that modifies Ftrans, i→k and n is the contact number. As an example, if Fmod, (j,k) = 0.1, for contact number 1 (n = 1), the modifier is 1.00, for contact number 2 (n = 2), the modifier is 0.905, for contact number 3 (n = 3), the modifier is 0.819, ….. .

The numbers of contacts of the different dermal surfaces with the different environmental surfaces are denoted by Ncon, (j,k). The units for this variables are in number of contacts per unit time (e.g., # contacts/hr). If an exposure duration is known (Texp), the total number of contacts during that duration is obtained by multiplying Ncon, (j,k) and Texp. Assumptions 1) Before, during, and after dermal surfaces contacts with the environmental surfaces, the concentrations of chemical on both, the environmental surfaces and the dermal surfaces, remain homogeneous.

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2) The mass in the environmental surfaces is assumed to be infinite. This gross assumption is interpreted as that every contact of a dermal surface with an environmental surface is with a new area. Usually, the transfer of chemical from the different environmental surfaces to the different dermal surfaces does not reach the limit of what is available. In the case where this is possible, the calculations have to be modified accordingly. A possible modification is used in Scenario 3. 3) When a dermal surface contacts an environmental surface, the entire dermal surface area is assumed to be in contact. Calculations Environmental surface zone j concentration (:g/cm2) = (mass in zone j) / (area of zone j)

CM F F

A Fjenv env chem j

env area j=

× ×

×,

,

Concentration of chemical dislodgeable from environmental surface zone j (:g/cm2) C C Fdis j j dis j, ,= ×

Ratio of areas, region k / zone j

RA FA Fj k

der area k

env area j( , )

,

,=

×

×

Normalized contribution of environmental surface zone j to dermal surface region k (�g/cm2) for Ncon, (j,k) contacts

( )( )( )C C F e Rk j dis j trans j k

F n

n

N T

j kj k

con j k

← →− × −

=

×= × ×

⎛

⎝⎜

⎞

⎠⎟∑ ×, , (

mod,( , ),( , ) exp 1

1, )

Concentration remaining in environmental surface zone j after Ncon, (j,k) contacts (:g/cm2)

( )( )( )C C F F e Rrem j j dis j trans j k

F n

n

N T

j kk

K j kcon j k

, , ,mod,( , )

,( , ) exp= × − × ×

⎛

⎝⎜

⎞

⎠⎟∑ ×

⎛

⎝

⎜⎜

⎞

⎠

⎟⎟∑

⎧

⎨⎪

⎩⎪

⎫

⎬⎪

⎭⎪→

− × −

=

×

=1

1

11( , )

Total mass on dermal surface region k (:g)

( )M A C Fk env k j area jj

J= × ×∑ ←

=,

1

Dermal surface region k concentration (�g/m2)

C MA Fk

k

der area k=

× ,

Total mass remaining on environmental surface in zone j (:g) M C A Frem j rem j env area j, ,= × × ,

Total mass on dermal surface (:g)

M Mder kk

K= ∑

=1

Total mass remaining on environmental surface (:g)

M Mrem env rem jj

J, ,= ∑

=1

Average fraction of chemical that can be dislodged from environmental surface

( )F F Fdis env dis zon j area jj

J, ,= ×∑

=1,

Transfer Factor for dermal surface region k from environmental surface zone j = (concentration in dermal surface region k) / (dislodgeable concentration in environmental surface zone j)

TFM

C A Fk jk

dis j der area k← =

× ×, .

Overall Transfer Factor for dermal surface region k = (concentration in dermal surface region k) / (dislodgeable concentration in total environmental surface)

TF CM F

A

kk

env dis env

env

=×⎛

⎝⎜

⎞

⎠⎟

,

Overall Transfer Factor = (concentration in total dermal surface) / (dislodgeable concentration in total environmental surface)

TF

MA

M FA

der

der

env dis env

env

=

⎛⎝⎜

⎞⎠⎟

×⎛

⎝⎜

⎞

⎠⎟

,

Transfer Coefficient for dermal surface region k (m2/hr) = (mass on dermal surface region k) / [ (exposure duration) x (dislodgeable concentration in total environmental surface) ]

TC M

TM F

A

kk

env dis env

env

=×

×exp

,

Overall Transfer Coefficient (cm2/hr) = (mass on total dermal surface) / [ (exposure duration) x (dislodgeable concentration in total environmental surface) ]

TC M

TM F

A

derenv dis env

env

=×

×exp

,

Relationship between TC and TF

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TCTF

AT

der=exp

(cm2/hr)

Scenario 2 Exposure medium: Environmental surface Environmental surface: Single Exposure route: Dermal contact Dermal surface: Single Inputs Menv mass of chemical applied to environmental surface (:g) Fenv fraction of chemical deposing on environmental surface Aenv area of environmental surface treated (cm2) Fdis fraction of chemical dislodgeable from environmental surface Ader area of dermal surface affected (cm2) Ftrans fraction of chemical transferred from environmental surface to dermal surface per

contact Fmod exponential factor that modifies Ftrans based on the contact number Ncon number of dermal surface contacts with environmental surface per hour (#/hr) Texp exposure duration (hr) Scenario 2 is a sub-set of Scenario 1 with J = 1 and K = 1. All uses of subscripts j and k have been removed. Assumptions The assumptions applied to Scenario 1 are also applied here. Calculations Environmental surface concentration (:g/cm2)

C M FAenv

env envenv

= ×

Amount of chemical dislodgeable from environmental surface (:g/cm2) C C Fdis env dis= ×

Ratio of areas, dermal / environmental

R AA

derenv

=

Normalized contribution of environmental surface to dermal surface (:g/cm2) for Ncon contacts

( )( )( )C C F eder env dis trans

F n

n

N Tcon

←− × −

=

×= × × ⎛

⎝⎜⎞⎠⎟∑ ×mod

exp 1

1R

Concentration remaining in environmental surface (:g/cm2)

( )( )( )C C F F erem env dis trans

F n

n

N Tcon= × − × × ⎛

⎝⎜⎞⎠⎟∑ ×

⎧⎨⎪

⎩⎪

⎫⎬⎪

⎭⎪

− × −

=

×1 1

1mod

expR

Total mass on dermal surface (:g) M A Cder env der env= × ←

Dermal surface concentration (�g/m2)

C MAder

derder

=

Total mass remaining on environmental surface (:g) M C Arem rem env= ×

Transfer Factor for dermal surface from environmental surface (based on dislodgeable concentration)

TF CC

derdis

=

Transfer Coefficient (cm2/hr) (based on dislodgeable concentration)

TC MT C

derdis

=×exp

Relationship between TC and TF TCTF

AT

der=exp

(cm2/hr)

Scenario 3 Exposure medium: Dermal surface on hands Exposure route: Oral (Hand-to-Mouth) Inputs Chand concentration of chemical on hand dermal surface (:g/cm2) Ahand area of hand dermal surface (cm2) Fdis fraction of chemical dislodgeable from hand dermal surface Acon area of hand dermal surface contacted by mouth during each contact (cm2) Ftrans fraction of chemical transferred from hand dermal surface to mouth per contact Ncon number of hand dermal surface contacts with mouth per hour (#/hr) Texp exposure duration (hr) Assumptions

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1) Before, during, and after contacts of the mouth with the hand dermal surface, the concentration of chemical on the hand dermal surface remains homogeneous. 2) The loss of mass in the hand dermal surface with every contact with the mouth is estimated and applied for subsequent contacts. 3) For each contact of the mouth with the hand dermal surface, the same fraction of the hand dermal surface area is assumed to be contacted. Calculations Concentration of chemical dislodgeable from hand dermal surface (:g/cm2)

C C Fdis hand dis= × Ratio of areas, contact / hand

R AA

conhand

=

Normalized contribution of hand dermal surface to mouth (:g/cm2) for (Ncon x Texp) contacts

( )( )( )C C F F R F F Rmouth hand hand dis trans dis trans

n

n

N Tcon

←−

=

×= × × × × − × ×∑ 1 1

1

exp

Concentration remaining in hand dermal surface (�g/cm2)

( )( )

C C F F Rrem hand dis transn

n

N Tcon= − ×∑

=

×1

1

exp×

Total mass in mouth (�g) M A Cmouth hand mouth hand= × ←

Total mass remaining on hand dermal surface (:g) M C Arem rem hand= ×

Transfer Factor for dermal surface from environmental surface (based on dislodgeable mass)

TF MMmouth

dis=

Transfer Coefficient (cm2/hr) (based on dislodgeable concentration)

TC MT C

mouthdis

=×exp

Micro-Based Dermal Exposure Methodology

As an alternative to the macro-based methods described above, Zartarian et al. (2000) have described a microactivity approach as incorporated into Residential SHEDS. Sequential dermal and nondietary ingestion exposure and dose time profiles are simulated by combining measured surface residues and residue transfer efficiencies with actual microlevel activity data

quantified from videotapes. Because the sequence of dermal loading and removal processes is preserved, such exposure profiles can improve estimates of time-dependent dermal absorption, which have traditionally assumed a fixed concentration at the skin surface. With information on frequency and duration of hand-to-mouth activities, these profiles can also improve estimates of ingested residues that are otherwise difficult to quantify. Exposure and dose profiles also provide various metrics of toxicological interest (e.g., peaks, averages, and instantaneous values) and information about the relative contribution of exposure pathways. When combined with activity data, profiles can provide information on how exposures and doses occur and how they can be mitigated.

The Residential-SHEDS algorithms are illustrated in TABLE A-5. For each specified exposure scenario, the model randomly selects an individual from the National Human Activity Pattern Survey (NHAPS) and simulates a sequence of object contact events (with object categories for smooth surface, textured surface, nothing, food, water, grass, and mouth) during each sequential location-activity combination reported in the individual's daily diary (Zartarian et al. 2000). Each object contacted is associated with an exposure pathway (i.e., skin-to-surface residue contact, skin-to-water contact, hand-to-mouth contact, or object-to-mouth contact) that allows the model to select the appropriate exposure and dose equation for each contact event. The model then performs time steps through every 5 sec interval in the simulated individual's day, combining proximity-specific surface residues with randomly sampled exposure factors for the appropriate pathway equation. The initial and final values are calculated for each sequential contact event in the person's database, and time profiles are generated for dermal exposure, nondietary ingestion, mass of metabolite in the blood compartment, and mass of metabolite eliminated using pathway-specific equations (TABLE A-5). Exposure and dose metrics of interest are extracted from the time profiles, and the entire process is repeated 1,500 times to yield histograms for the specified exposure scenario (Zartarian et al. 2000).

Model assumptions. Residential-SHEDS currently assumes simple first-order linear

absorption from the skin and gastrointestinal tract into the body and first-order urinary elimination of the pesticide metabolite from the body. The model construct contains a number of other assumptions that can be refined with more research. For example, removal and loading of chemicals at the skin surface is assumed to be instantaneous and independent of number of skin-to-surface contacts, and the model does not track which portion of the skin contacts residue from one contact event to the next. For a given application method and postapplication time, deposited concentrations on targeted surfaces are assumed to be the same throughout a residence; nontargeted surfaces in the same residence are also assumed to be uniform, but may be different from targeted surfaces. Surface residue loadings are resampled for each simulated residence. The model time step is on the order of seconds (based on available skin-to-surface contact duration data), except during sleeping activities, when 30 min is used (the optimal time step for minimizing error in approximating the exact analytical solution to the differential exposure and dose equations with numerical difference equations). Because little information is available on the physical and chemical fate of pesticide residues indoors, nonparticle-bound residues are assumed for up to 30 days postapplication, and aerosol deposition and evaporation at the skin surface are not currently included. The individuals sampled are assumed to live in residences with independent indoor and lawn pesticide applications. The initial daily exposure and dose is assumed to be zero for a given individual. During a sleeping event the child's skin is assumed to

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contact nontargeted surface residues. Legs, arms, torso, and feet are treated as a single skin surface because body-part-specific microactivity data are currently lacking, except for hands and mouth. Because of the lack of data concerning the penetration of pesticide residues through clothing and the percent of skin surface that is clothed, the role of clothing is currently neglected in the model.

Residential-SHEDS is a useful tool for identifying data needs to encourage research so that the model can be evaluated and used reliably to make predictions when measurements are not feasible. In particular, the model can be used now as a research tool to identify critical data needs and relative contributions of pathways and model inputs, and can be used for regulatory purposes after it has been evaluated.

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REFERENCES Abrams, H.K. and A.R. Leonard. 1950. Toxicology of Organic Phosphate Insecticides. California Medicine, Vol. 73, No. 2:183-186. Archibald, B.A., K.R. Solomon, and G.R. Stephenson. 1994. A New Procedure for Calibrating the Video Imaging Technique for Assessing Dermal Exposure to Pesticides. Archives of Environmental Contamination and Toxicology, 26:398-402. Archibald, B.A., K.R. Solomon, and G.R. Stephenson. 1995. Estimation of Pesticide Exposure to Greenhouse Applicators Using Video Imaging and Other Assessment Techniques. American Industrial Hygiene Association Journal, 56:226-235. Black, K.G., and R.A. Fenske. 1996. Dislogeability of Chlorpyrifos and Flourescent Tracer Residues on Turf: Comparison of Wipe and Foliar Sampling Techniques. Archives of Environmental Contamination and Toxicology, 31:563-570. Davis, J.E., E.R. Stevens, and D.C. Staiff. 1983. Potential Exposure of Apple Thinners the Azinphosmethyl and Comparison to Two Methods for Assessment of Hand Exposure. Bulletin of Environmental Contamination and Toxicology, 31:631-638. Driver, J.H. and G.K. Whitmyre. 1997. Pesticide regulation and human health: the role of risk assessment. IN: Fundamentals of Risk Analysis and Risk Management, Molak, V., ed. CRC Lewis Publishers, New York, NY. pp. 143-162. Driver, J.H., G.K. Whitmyre, J.J. Konz, T.A. Roy, J.J. Yang and A.J. Krueger. 1989. Dermal exposure assessment for toxicants in soil: soil adherence to skin and dermal bioavailability. IN: Total Exposure Assessment Methodology: A New Horizon. Proceedings of the EPA & A&WMA Specialty Conference. November, 1989, Las Vegas, NV. pp 597-618. Driver, J.H., J.J. Konz and G.K. Whitmyre. 1989. Soil adherence to human skin. Bull of Environ Contam Toxicol 43:814-820. Durham, W.F., and H.R. Wolfe. 1962. Measurement of the Exposure of Workers to Pesticides. Bulletin of the World Health Organization, 26:75-91. Fenske, R. and C. Lu. 1994. Determination of Handwash Removal Efficiency: Incomplete Removal of the Pesticide Chlorpyrifos from Skin by Standard Handwash Techniques. American Industrial Hygiene Association Journal, 55(5):425-432. Fenske, R.A., K.G. Black, K.P. Elkner, C. Lee, M.M. Methner and R. Soto. 1990. Potential exposure and health risks of infants following indoor residential pesticide applications. AJPH. 80:689-693.

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Furtaw EJ, M.D. Pandian, and J.V. Behar. 1993. Human exposure in residences to benzene vapors from attached garages. Paper presented at and published in the proceedings of The International Conference: Indoor Air '93, Helsinki, Finland, July 1993. Harris, S.A. and K.R. Solomon. 1992. Human Exposure to 2,4-D Following Controlled Activities on Recently Sprayed Turf. Journal of Environmental Science and Health, B27(1):9-22. Harris, S.A., K.R. Solomon, and G.R. Stephenson. 1992. Exposure of Homeowners and Bystanders to 2,4-dicholorphenoxyacetic Acid (2,4-D). Journal of Environmental Science and Health, B27(1):23-38. Hubal, Cohen E, K. Thomas, J. Quackenboss, E. Furtaw, L. Sheldon. 1999. Dermal and Non-Dietary Ingestion Workshop. EPA 600/R-99/039. Research Triangle Park, NC:U.S. Environmental Protection Agency, 1999. ILSI (International Life Science Institute). 1998. Aggregate Exposure Assessment for Pesticides. Proceedings of the Aggregate Exposure Assessment Workshop, February 9-10, 1998. Organized by the ILSI Risk Science Institute, Washington DC. Krieger R ; Blewett C ; Edmiston S ; Fong H ; Gibbons D ; Meinders D ; O'Connell L ; Ross J ; Schneider F ; Spencer. 1990. Gauging pesticide exposure of handlers (mixer/loaders/applicators) and harvesters in California agriculture. J. Medicina del Lavoro Nov.-Dec., Vol.81, No.6, p.474-479. Lewis, R.G., R.C. Fortmann, D.E. Camann. 1994. Evaluation of Methods for Monitoring the Potential Exposure of Small Children to Pesticides in the Residential Environment. Archives of Environmental Contamination and Toxicology, 26:37-46. Lioy, P.J., T. Wainman, and C. Weisel. 1993. A Wipe Sampler for the Quantitative Measurement of Dust on Smooth Surfaces: Laboratory Performance Studies. Journal of Exposure Analysis and Environmental Epidemiology, 3:315-330. Matoba, Y. 1996. Simulation of indoor behavior of insecticides applied by various methods. In: SP World, No. 24. Sumitomo Chemical Company, Ltd., Osaka, JAPAN. McKone, T.E. 1991. Human exposure to chemicals from multiple media and through multiple pathways: Research overview and comments. Risk Analysis 11 (1): 5-10. Ott, W.R. 1985. Total human exposure: an emerging science focuses on humans as receptors of environmental pollution. Environ. Sci. Technol. 19:880. Popendorf, W.J. 1976. An Industrial Hygiene Investigation into the Occupational Hazards of Parathion Residues to Citrus Harvesters. Dissertation for Doctor of Philosophy in Environmental Health Sciences in the Graduate Division of the University of California, Berkeley.

Popendorf, W.J. 1985. Advances in the unified field model for reentry hazards. IN: Dermal Exposure Related to Pesticide Use: Discussion of Risk Assessment, Honeycutt, R.C., G. Zweig and N.N. Ragsdale, Eds, American Chemical Society, ACS Symposium Series 273, Washington, D.C. Roberts, J.W., W.T. Budd, M.G. Ruby, D.E. Camann, R.C. Fortmann, R.G. Lewis, L.A. Wallace, and T.M. Spittler. 1992. Human exposure to pollutants in the floor dust of homes and offices. J. Exposure Anal. Environ. Epidemiol. 1(Suppl. 1):127-146. Ross, J.H., T. Thongsinthusak, H.R. Fong, S. Margetich, and R. Krieger. 1990. Measuring Potential Dermal Transfer of Surface Pesticide Residue Generated from Indoor Fogger Use: An Interim Report. Chemosphere, Vol.20, Nos. 3/4:349-360. Ross, J.H., H.R. Fong, T. Thongsinthusak, S. Margetich, and R. Krieger. 1991. Measuring Potential Dermal Transfer of Surface Pesticide Residue Generated from Indoor Fogger Use: Using the CDFA Roller Method. Interim Report II. Chemosphere, Vol.22. Nos.9-10:975-984. USEPA (U.S. Environmental Protection Agency). 1990. Non-Occupational Pesticide Exposure Study (NOPES). Report No. EPA/600/3-90/003, USEPA, Research Triangle Park, N.C. pp. 2-3. USEPA (U.S. Environmental Protection Agency). 1992. Dermal Exposure Assessment: Principles and Applications. Washington, DC: Exposure Assessment Group, Office of Health and Environmental Assessment, Office of Research and Development. EPA Publication No. 600/8-91-011. USEPA (U.S. Environmental Protection Agency). 1996. Comparison of Methods to Determine Dislodgeable Residue Transfer from Floors. Report No. EPA/600/R-96/089, USEPA, Research Triangle Park, N.C. USEPA (U.S. Environmental Protection Agency). 1999a. Overview of Issues Related to the Standard Operating Procedures for Residential Exposure Assessment. Presented to the EPA Science Advisory Panel for the meeting on September 21, 1999. U.S. EPA, OPP, Washington, D.C. USEPA (U.S. Environmental Protection Agency). 1999b. Exposure Factors Handbook. National Center for Environmental Assessment, Cincinnati, OH.. USEPA Publication No. EPA/600/C-99/001, February 1999. Vaccaro, J.R., R.J. Nolan, P.G. Murphy, and D.B. Berbrich. 1996. The Use of Unique Study Design to Estimate Exposure of Adults and Children to Surface and Airborne Chemicals. American Society for Testing and Materials, West Conshohocken, PA, Std. Tech. Publ. 1287, pp.166-183. Zartarian, V.G., A.C. Ferguson, and J.O. Leckie. 1997. Quantified Dermal Activity Data from a Four-Child Pilot Field Study. Submitted to the Journal of Exposure Analysis and Environmental Epidemiology.

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Zartarian, V.G., J. Streicker, A Rivera, C. Cornejo, S. Molina, O. Valdez, and J.O. Leckie. 1995. A Pilot Study to Collect Micro-Activity Data of 2-4 Year-Old Farm Labor Children in Salinas Valley, California. Journal of Exposure Analysis and Environmental Epidemiology, 5(1):21-24. Zartarian, V.G. and J.O. Leckie. 1998. Dermal exposure: the missing link. Envr Sci & Tech. March 1, 1998, pp. 134-137. Zartarian, V.G., H. Ozkaynak, J.M. Burke, M.J. Zufall, M.L. Rigas and E.J. Furtaw. 2000. A modeling framework for estimating children’s residential exposure and dose to chlorpyrifos via dermal route and nondietary ingestion. Environ. Health Perspect. 108:505-514. Zweig, G., R. Gao, and W. Popendorf. 1983. Simultaneous Dermal Exposure to Captan and Benomyl by Strawberry Harvesters. Journal of Agricultural Food Chemistry, 31:1109-1113.