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

Measurement techniques -principles and methods

John Cherrie

Summary…

• The ideal

• Pragmatic methods to measure dermal exposure

• Interception

• Removal

• Fluorescence

• Biological monitoring

• Other approaches

• Interpreting these measurements

Ideally…

• We would measure the uptake of a substance through the skin

• Uptake depends on…

• The concentration of the substance on the skin

• The area of skin exposed

• The duration of exposure

• The mass of contaminant on the skin

• The integrity of the startum corneum

and several other factors…

• This is difficult to do and so we don’t do it!

Direct and indirect methods…

• Direct methods

• Measurement of contaminant material on

the skin or clothing

• Indirect methods

• Measurement of other compartments

(e.g. Msurface)

• Biological monitoring

• Modelling dermal exposure

Direct methods…

• Interception methods/surrogate skin

• Patch

• Whole body suit

• Removal

• Wash

• Wipe

• Tape stripping

• Visualisation techniques

• Fluorescence techniques, e.g. VITAE or

FIVES

What do we measure?

• Interception

• The mass of chemical that lands on the skin

over the sampling time (integrated flux)

• Removal

• The mass of contaminant left on the skin

• Fluorescent tracers

• The mass of a surrogate compound retained

on the skin

Interception sampling…

Actual and potential exposure…

• Actual

• Measured directly on skin

• May still be collecting whatever lands on the skin

• Potential

• Measured on clothing not skin

• A measure of the maximum possible exposure, i.e. not account taken of the reduction due to clothing barrier

Interception methods…

• Patch methods• 6-11 patches distributed over the body

surface

• each patch 100cm2

• cotton, gauze, paper, charcoal cloth

• Gloves• each hand

• cotton

• Whole body• coverall

• 20,000cm2

• cotton

Interception method problems…

• Patch methods have different protocols

• WHO method (6 patches) - 3% body surface

• OECD method (11 patches) - 8% body surface

• involves extrapolation

• Whole body sampling has practical issues

• requires large volume of solvent for extraction of substance (as much as 1.5 litres leading to high limit of quantification)

Indicators…

Removal techniques…

• Washing – hands

• flow into a capture container

• use water or solvent

• Rinsing – hands

• in bag

• use water or solvent

• Wipe – any body area

• travel/baby wipes or dry cloth

• Stripping skin – any body area

• adhesive tape

• measures percutaneous absorption not exposure

Removal techniques…

Removal techniques

Tape stripping

Removal sampling…

Removal efficiency…

• Ranges from 40-95%

• Depends on

• loading

• time of residence on the skin

• material/solvent type used

• number and duration of

wash/rinse/wipes

• operator variability: e.g. pressure of

wipe

Visualisation techniques…

• Tracer

• Image acquisition

• Image processing

• Calculation of exposure

• VITAE

• Video Imaging Technique to Assess Dermal

Exposure

• FIVES

• Fluorescent Interactive Video Exposure System

Fluorescent tracers…

Fluorescent tracer systems…

Visualisation problems…

• Disadvantages

• Need to be able to add

tracer

• High investment

• Highly skilled operator

• Fluorescence binds to

skin for >3 days

• Advantages

• no chemical analysis

• provides instant feedback

to exposed individuals

Biological monitoring…

• Quantitative measurement substances/metabolites in biological media

• invasive: blood

• non-invasive: urine, breath, saliva

• Actual absorption by all routes

• Indicates internal dose

• relevant for risk assessment

Interpreting biological monitoring…

• Pharmacokinetic and/or pharmacodynamic data

• metabolites of dermal application

• volunteer studies - use for skin penetration studies

• inter-individual human differences

• Collection strategy

• period of time excretion completed

Suitability of monitoring methods…

Surrogate

skin &

Fluorescence

techniques

Removal &

fluorescence

techniques

Biological monitoring

Removal + resuspension /

evaporation rate (g/s)

Pe

rme

atio

n/p

en

etr

ati

on

ra

te (

g/s

)high

highlow

Conclusions…

• Measurement of dermal exposure is based on pragmatic methods

• All approaches give some information about dermal exposure

• None of the methods is ideal and data from one approach can’t be directly compared with others