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