INSTITUTE OF OCCUPATIONAL MEDICINE . Edinburgh . UK www.iom-world.org

Modelling: Available approaches

John Cherrie

Summary…

• Why use models?

• Examples of dermal modelling tools

• Advantages and disadvantages of modelling approaches

MeasurementTheory

Why do we need model tools?

• Models are representations of reality

• They are useful for predicting exposure

• They provide a basis for documenting the measurement scenario

MeasurementTheory

Routes of exposure…

• Inhalation exposure (mg/m3)

• Ingestion (mg/day)

• Dermal exposure (mg or mg/cm2)

Inhalation

Ingestion

Skin

uptake

• Ideally, we would have all measures on the same basis, i.e. uptake/intake (mg) into the body

A conceptual model…

Surface contamination

layer Air compartment

Clothing outer layer

Skin contamination layer

Source

Clothing inner layer

Schneider et al. Conceptual model for assessment of dermal exposure. Occup Environ

Med (1999) vol. 56 (11) pp. 765-73

Tools for estimating exposure…

• ConsExpo (by RIVM)

• Estimates dermal exposure to consumer products

• http://www.rivm.nl/en/healthanddisease/productsafety/ConsExpo.jsp

• ECETOC TRA (Targeted Risk Assessment for REACH), variant of EASE

• http://www.ecetoc.org/tra

• RISKOFDERM (TNO, task-based approach relying on similar dermal exposure operation units)

• Incorporated in www.StoffenManager.nl

• DREAM (DeRmal Exposure Assessment Method)

• Derived from Schneider’s conceptual model

• Generates a relative index of exposure

ConsExpo…

• ConsExpo is a toolbox of models for inhalation and dermal exposure

• Relaunched as a web tool

• https://www.consexpoweb.nl

• Needs considerable expertise to use

• Tailored to consumers not workers

• Children's toys

• Cleaning

products

• Cosmetics

• Disinfectants

• Paint products

• Pest control

ECETOC TRA

• Designed as a screening tool for use with the REACH Regulations in Europe

• Based on the EASE tool, originally produced by the UK HSE

• Now in version 3.1

• Uses hands, forearms and face as target exposed area

• “Model has limited scientific foundation for dermal exposure”

http://www.ecetoc.org/tools/targeted-risk-assessment-tra/

ECETOC TRA…

• The model estimates exposure (mg/kg/day) using information on:

• Process categories (PROCs)

• Industrial or professional use

• LEV use

• Solid / liquid

• Dustiness / vapour pressure

• Concentration

• Duration of exposure

• Glove use

Evaluation of the TRA…

• Marquart et al from TNO published an evaluation of the dermal tool

• Compared estimates for 110 scenarios with corresponding measurement data

• Each scenario independently scored by 3 or 4 experts

• Underestimation in 20% of the cases (Estimate versus 75th percentile)

• Model explained 37% of the variance

Marquart H, Franken R, Goede H, Fransman W, Schinkel J. Validation of the dermal exposure model in

ECETOC TRA. Annals of Work Exposures and Health 2017 Jul 25;61(7):854–71.

Marquart et al data

Riskofderm…

• An empirical model tool based on the analysis of a relatively large dataset

• Data from five different European countries over the period 1996–2006

• more than 500 data sets for hand exposure and

• more than 600 data sets for body exposure

• Estimates are for task-based assessments of potential dermal exposure

• six dermal exposure operation (DEO) units

• Assumes assessments are substance independent

DEO units

1. Handling contaminated objects / mixing, filling and loading

2. Wiping on a surface

3. Dispersion with a hand-held tool

4. Spraying

5. Immersion of objects into baths etc

6. Mechanical treatment of solid objects, e.g. grinding

Riskofderm

Model

parameters

Riskofderm models…

• Linear mixed effects models were fitted using restricted maximum likelihood estimation

• Different model for each DEO

• Predict median potential dermal exposure rates

• for the hands and

• the rest of the body

• These rates are expressed as mg or ml product per minute

Advantages

• Based on measurements

• Easy to use

• Duration of task considered

Limitations

• Limited by data sets behind DEOs

• Can only consider one task

• Only estimates potential exposure

• Doesn’t consider vapour pressure or concentration

• Doesn’t account for different routes of exposure

DREAM model…

• Based on the Schneider et al model

• Complex deterministic algorithm

• Estimates are reasonably reproducible between assessors

• Only provides estimates in “Dream Units” - DU

van Wendel de Joode et al. Accuracy of a semiquantitative method for Dermal

Exposure Assessment (DREAM). Occup Environ Med (2005) vol. 62 (9) pp. 623-32

DREAM

Exposure Assessors estimate exposure from each of the three pathways of dermal exposure:

• Immersion

• Surface Contact

• Deposition

Substance

characteristics

Skin area

exposedNumber of

exposure events

ctorotectionFaClothingPr

Emission IntrinsicIntensityFrequencysureDermalExpo

xx

DREAM…

van Wendel de Joode et al. DREAM: A method for semi-quantitative dermal

exposure assessment. Annals of Occupational Hygiene (2003) vol. 47 (1) pp. 71-87

Emission

Deposition

Transfer

Clothing

Body surface factor

DREAM validations…

van Wendel de Joode et al (2005)

GULF DREAM…

• This updates the DREAM model using latest published data, in the context of the Deepwater Horizon disaster research studies

• Similar model structure – implemented in an EXCEL spreadsheet

• Limited validation with asphalt and heavy fuel oil data

Updating DREAM

• Updated/reviewed literature on model parameters relevant to GuLF STUDY:

• viscosity and stickiness

• evaporation

• gloves and protective clothing

• seawater and sweat

• sun screens & insect repellents

• Other variables amended as necessary based on recent literature

Limited validation / calibration…

Regression analysis

Ln M = -0.337 + 1.167 * Ln E

Where:

M = measured exposure (µg/m2)

E = estimated exposure (GDU)

R = 0.59

Advantages

• Different routes of exposure considered

• Actual exposure is estimated

• Vapour pressure and concentration is accounted for

• Wind speed can be accounted for

Limitations

• More complex

• Subjectivity in assignment of intensity and frequency of exposure

• Only appears to work for hand wiping and washing methods

• Can only consider one task

• Duration of task not considered

• Not fully validated

Tools for estimating uptake…

• NIOSH Skin Permation Calculator

• http://www.cdc.gov/niosh/topics/skin/skinPermCalc.html

• IH SkinPerm

• http://www.aiha.org/get-involved/VolunteerGroups/Pages/Exposure-Assessment-Strategies-Committee.aspx

• These models are based on maximum flux from an area of skin exposed not mass loading

A practical example…

• Use of Riskofderm and IH SkinPerm

• Spreading rubber compound onto cloth before it was pressed by rollers on a spreading machine. The rubber compound had around 10% toluene

• Riskofderm predicts median dermal loading of toluene on the hands to be around 750 mg; 90th

percentile is 16,000 mg

• IH-Skinperm shows that over a 4-hours around 93% of toluene evaporates and only around 50 mg absorbed in to the skin

• Inhaled intake around 592mg (i.e. 98 mg/m3 x 240 min x 0.025 m3/min)

Summary…

• The conceptual dermal model can aid understanding

• There are a range of practical model tools that can be used

• All have limitations and some advantages

• Combining an exposure model and uptake assessment can provide a way of interpreting dermal exposure