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

Exposure Judgment: Improving Inhalation, Dermal & Noise Assessment

Dermal exposure

John Cherrie

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

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

Structure of the skin…

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

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.

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.

Key factors for uptake…

• Mass on skin• Concentration of contaminant• Area exposed• Duration of exposure• Skin condition

Key factors for uptake…

• Mass on skin• Concentration of

contaminant• Area exposed• Duration of exposure• Skin condition

Key factors for uptake…

• Concentration of contaminant• Mass on skin• Area exposed• Duration of exposure• Skin condition

Key factors for uptake…

• Mass on skin• Concentration of contaminant• Area exposed• Duration of exposure• Skin condition

Washed off

Key factors for uptake…

• Mass on skin• Concentration of contaminant• Area exposed• Duration of exposure• Skin condition

Contact dermatitis…

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

Workplaces where dermal exposure is important

• Painters• Petrochemicals• Dry cleaners• Farmers• Crop-harvesters• Shoe manufacturers• Engineers• Hairdressers, nurses and

many, many more…

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

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

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.

Different process – different pathways

Curing Pre-treatment

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

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

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.

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%

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

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

Removal sampling…

26

Fluorescence tracers…

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

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

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

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

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

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

Questions?

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