An introduction to dermal exposure assessment
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INSTITUTE OF OCCUPATIONAL MEDICINE . Edinburgh . UK www.iom-world.org
Exposure Judgment: Improving Inhalation, Dermal & Noise Assessment
Dermal exposure
John Cherrie
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Summary…
• The skin and chemicals• Adverse effects• Routes of exposure and uptake• Solids, liquids and gases• A conceptual model of skin
exposure• Measuring dermal exposure• Modeling exposure and uptake• Control and personal protection
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The skin…
• Two-way protective barrier
• About 2m2 area for an adult
• Hands comprise about 5% and arms 15% of area
• Complex structure that is metabolically active
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Structure of the skin…
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Dermal permeation of chemicals…
• Uptake by diffusion• Maximum flux at steady-state (Jmax,ss)
€
Jmax,ss =Ssc .D
h
Where, Ssc is the saturated concentration of solute in the stratum corneum D is the diffusion coefficient h the thickness of the stratum
corneum
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Flux and molecular weight…
Magnusson, Anissimov, Cross, and Roberts. Molecular Size as the Main Determinant of Solute Maximum Flux Across the Skin. J Invest Dermatol 122:993 –999, 2004.
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Solids, liquids and gases
• Solids• Must dissolve in sweat before being taken up• Or, particles must be small and skin barrier
disrupted
• Liquids• Must be less than about 500 Dalton• Volatile liquids may evaporate quickly
• Gases and vapors• Almost always have very low dermal uptake• Some exceptions: e.g. 1-methoxy-2-propanol and
2-butoxyethanol
Kielhorn J, Melching-Kollmub S, Mangelsdorf I (2006) Dermal absorption. EHC 235.
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Key factors for uptake…
• Mass on skin• Concentration of contaminant• Area exposed• Duration of exposure• Skin condition
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Key factors for uptake…
• Mass on skin• Concentration of
contaminant• Area exposed• Duration of exposure• Skin condition
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Key factors for uptake…
• Concentration of contaminant• Mass on skin• Area exposed• Duration of exposure• Skin condition
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Key factors for uptake…
• Mass on skin• Concentration of contaminant• Area exposed• Duration of exposure• Skin condition
Washed off
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Key factors for uptake…
• Mass on skin• Concentration of contaminant• Area exposed• Duration of exposure• Skin condition
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Contact dermatitis…
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Systemic effects… • Some chemicals can pass through the
unbroken skin and contribute to total body burden
• Solvents, metals, pesticides…• No dermal workplace exposure limits• Many chemicals show a theoretical
potential for dermal absorption or toxicity, only but only a small fraction have a skin notation (Sk)
• NIOSH has new publications on skin notation
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Workplaces where dermal exposure is important
• Painters• Petrochemicals• Dry cleaners• Farmers• Crop-harvesters• Shoe manufacturers• Engineers• Hairdressers, nurses and
many, many more…
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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 (mg) into the body
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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
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Rubber industry study…
• Identified the exposure pathways in rubber manufacturing
• They measured…• Air concentration – both near and far-field• Dermal loading
• They showed that…• Hand (wrist) contamination was on average
highest• Strong correlation between hand (wrist) and
whole body contamination
Vermeulen R, Heideman J, Bos RP, Kromhout H. (2000) Identification of dermal exposure pathways in the rubber manufacturing industry. Ann Occup Hyg.;44(7):533-541.
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Different process – different pathways
Curing Pre-treatment
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Inhalation and dermal exposure…• Searching Scopus database for entries
since 2000• Search query: (inhalation) AND (dermal)
AND (exposure) AND (occupational OR worker)
• 361 papers• Screening on title gave about 60 possibly
informative papers• Screening on abstract identified more than
half of these as uninformative
• Final assessment based on about 20 papers
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Inhalation and dermal exposure
Authors Substance Workplace Corr Comment
Fent et al (2008) HDI Spray painters
0.79 Log transformed data
Day et al (2007) Beryllium Cu-Be alloy plant
0.63
McClean et al (2004) PAH Asphalt workers
0.59 Based on pyrene analysis
Hughson et al (2010) Nickel Various Ni production
0.48 Long-transformed hand data
Sobus et al (2009) PAH Asphalt workers
0.32 Not statistically significant
Cocker et al (2009) MbOCA Polyurethane elastomers
None
Aprea et al (2009) Imidacloprid Greenhouse None
21
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Fent et al (2008)
Fent K, Jayaraj K, Ball LM, Nylander-French L. (2008) Quantitative monitoring of dermal and inhalation exposure to 1,6-hexamethylene diisocyanate monomer and oligomers. J. Environ. Monit.;10(4):500-507.
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Contribution to all exposure…
Authors Substance Workplace % skin
Comment
Borak et al (2002) PAH Creosote impregnation >90%
Aprea et al (2009) Imidacloprid Greenhouse work >78%
Est. absorbed dose
Sheenan et al (2008) Benzene Cleaning ≈50% Low levels
Bader et al (2008) NMP Simulation 47% Vapour uptake at rest
Chen et al (2008) PAH Metal machining 37%
Lindsay et al (2006) Toluene Coating work <9%
Kim et al (2007) Jet fuel Fuel cell maintenance 4% PBTK model
Chao et al (2006) Jet fuel Fuel cell maintenance 3%
Wang et al (2013) Flame retardant
Recycling 1% Most from diet
Xing et al (2011) PCB Recycling 0% Most from diet
Vermeulen (2006) Benzene Shoe manufacture 0%
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How do we measure?
• Interception (e.g. patches)• The mass of chemical that lands on the skin
over the sampling time (integrated flux)
• Removal (e.g. wipe/wash)• The mass of contaminant left on the skin
• In-situ (e.g. fluorescence)• The mass of a surrogate
compound retained on the skin
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Interception sampling…
• ‘Generic’ protocols that prescribe sizes, numbers, location and method of attachment of patches are given by WHO, US-EPA, OECD
• Possible to use whole suit, gloves, hood, socks…
• “actual” and “potential” exposure
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Removal sampling…
26
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Fluorescence tracers…
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Tools for estimating exposure…• ConsExpo (by RIVM)
• Estimates dermal exposure to consumer products• http://www.rivm.nl/en/healthanddisease/productsafety/Con
sExpo.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
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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/Ex
posure-Assessment-Strategies-Committee.aspx
• These models are based on maximum flux from an area of skin exposed not mass loading
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Preventing dermal exposure…
• Elimination of the dermal hazard• Change the work method so exposure
is no longer necessary• Substituting with lower hazard
materials• Using a different form of the material
to prevent exposure• Safe working distance• Total enclosure• Partial enclosure
• Local exhaust ventilation• Process changes• Administrative changes• PPE
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Safe Working Distance
• Use a tool to prevent contact between hands and fluid• Scrubbing brush• Scoop• Long handles
• Avoid immersion events• Use gloves if SWD not
possible• Avoid repeated cycles
of wet/dry• Can work be batched
rather than continuous
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Protective clothing…
• Any protective clothing between the skin, or normal clothing, and the outside world• gloves• overalls• boots • hoods• chemical suits
• Clothing is less effective in practice than might be expected from laboratory tests
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Conclusions…
• Dermal exposure may contribute importantly to total exposure
• We understand the skin exposure at a conceptual level
• Skin exposure may or may not be associated with inhalation exposure
• Interpreting measurements is not straightforward
• Control can be more than protective clothing